@article {pmid37278910, year = {2023}, author = {Ha, MV and McCormick, TS and Salem, I and Al-Shakhshir, H and Ghannoum, MA and Carroll, BT}, title = {Skin and gut microbial associations with squamous cell carcinoma in solid organ transplant recipients.}, journal = {Archives of dermatological research}, volume = {}, number = {}, pages = {}, pmid = {37278910}, issn = {1432-069X}, support = {P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; }, abstract = {Solid organ transplant recipients (SOTRs) are burdened with a significantly higher risk of squamous cell carcinoma (SCC) compared to the general population. Accumulating evidence suggests the potential influence of microbial dysbiosis on transplant outcomes. Based on these observations, we sought to identify differences in the cutaneous and gut microbiomes of SOTRs with and without a history of SCC. This case-control study collected and analyzed non-lesional skin and fecal samples of 20 SOTRs > 18 years old with either ≥ 4 diagnoses of SCC since most recent transplant (n = 10) or 0 diagnoses of SCC (n = 10). The skin and gut microbiomes were investigated with Next-Generation Sequencing, and analysis of variance (ANOVA) followed by Tukey pairwise comparison procedure was used to test for differences in taxonomic relative abundances and microbial diversity indices between the two cohorts. Analyses of the skin microbiome showed increased bacterial and reduced fungal diversity in SOTRs with a history of SCC compared to SOTRs without a history of SCC (bacterial median Shannon diversity index (SDI) = 3.636 and 3.154, p < 0.05; fungal SDI = 4.474 and 6.174, p < 0.05, respectively). Analyses of the gut microbiome showed reduced bacterial and fungal diversity in the SCC history cohort compared to the SCC history-negative cohort (bacterial SDI = 2.620 and 3.300, p < 0.05; fungal SDI = 3.490 and 3.812, p < 0.05, respectively). The results of this pilot study thus show a trend toward the bacterial and fungal communities of the gut and skin being distinct in SOTRs with a history of SCC compared to SOTRs without a history of SCC. It furthermore demonstrates the potential for microbial markers to be used in the prognostication of squamous cell carcinoma risk in solid organ transplant recipients.}, } @article {pmid37278206, year = {2023}, author = {Li, R and Xu, S and Li, B and Zhang, B and Chen, W and Dai, D and Liu, Z}, title = {Gut indigenous Ruminococcus gnavus alleviates constipation and stress-related behaviors in mice with loperamide-induced constipation.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2fo03574j}, pmid = {37278206}, issn = {2042-650X}, abstract = {Refractory constipation is the most severe form of constipation, and its etiology remains unknown. The symptoms of constipation occur repeatedly, which brings great pain to the patient's body and psychology. Accumulating studies suggest that constipation patients present a significant dysbiosis of the gut microbiota compared with healthy individuals. In this study, we analyzed the gut microbiota composition of fresh feces and accumulated feces (old feces) of patients with refractory constipation and found that there was a significant difference between them. Through a mouse model of loperamide-induced constipation, it was proved that the old feces of patients with refractory constipation could aggravate the constipation symptoms in mice, while the fresh feces could alleviate the symptoms, which is consistent with the effect of feces from healthy volunteers in a mouse model of loperamide-induced constipation. We identified an indigenous strain Ruminococcus gnavus (R. gnavus), which is highly enriched in the fresh feces of patients with refractory constipation, and found that oral administration of R. gnavus could effectively improve the constipation symptoms in mice with constipation induced by loperamide and fecal bacteria transplanted from patients with constipation and significantly improve the stress-related behaviors of mice. This result may be related to the regulation of intestinal muc2, c-kit, sert and other gene expression by R. gnavus and the control of somatostatin (SS) and motilin (MTL) production. Our results suggest that gut microbe intervention with indigenous strains such as R. gnavus is a potential and promising alternative for the treatment of constipation, especially for refractory constipation.}, } @article {pmid37278059, year = {2023}, author = {Liu, L and Wu, Q and Chen, Y and Ren, H and Zhang, Q and Yang, H and Zhang, W and Ding, T and Wang, S and Zhang, Y and Liu, Y and Sun, J}, title = {Gut microbiota in chronic pain: Novel insights into mechanisms and promising therapeutic strategies.}, journal = {International immunopharmacology}, volume = {115}, number = {}, pages = {109685}, doi = {10.1016/j.intimp.2023.109685}, pmid = {37278059}, issn = {1878-1705}, abstract = {Chronic pain remains one of the world's most persistent and unsolved clinical challenges that severely affect patients' quality of life. Presently, considering that the mechanisms underlying chronic pain are not fully understood, there is a lack of effective drugs and interventions to treat chronic pain in clinical practice. Therefore, exploring the pathogenic mechanism of chronic pain and establishing potential targets are the keys to treating chronic pain. Substantial evidence has indicated that gut microbiota plays a crucial role in modulating chronic pain, which has opened up a new frontier for investigating the pathogenesis of chronic pain. The gut microbiota is a pivotal junction point between the neuroimmune-endocrine and the microbiome-gut-brain axes that could directly or indirectly affect chronic pain. Different signaling molecules (such as metabolites, neuromodulators, neuropeptides, and neurotransmitters) from the gut microbiota regulate the progress of chronic pain by modulating the peripheral and central sensitization by targeting the corresponding receptors. Furthermore, gut microbiota dysbiosis is associated with the progress of different chronic pain disorders, such as visceral pain, neuropathic pain, inflammatory pain, migraine, and fibromyalgia. Therefore, the present review attempted to systematically summarize the action of the gut microbiota toward regulating the pathological mechanisms of chronic pain and discussed the beneficial effects of probiotics supplementation or fecal microbiota transplantation (FMT) to restore the gut microbiota in chronic pain patients so as to provide a new strategy for targeting the gut microbiota for alleviating chronic pain issues.}, } @article {pmid37276766, year = {2023}, author = {Lund, MC and Larsen, BB and Rowsey, DM and Otto, HW and Gryseels, S and Kraberger, S and Custer, JM and Steger, L and Yule, KM and Harris, RE and Worobey, M and Van Doorslaer, K and Upham, NS and Varsani, A}, title = {Using archived and biocollection samples towards deciphering the DNA virus diversity associated with rodent species in the families cricetidae and heteromyidae.}, journal = {Virology}, volume = {585}, number = {}, pages = {42-60}, doi = {10.1016/j.virol.2023.05.006}, pmid = {37276766}, issn = {1096-0341}, abstract = {Rodentia is the most speciose order of mammals, and they are known to harbor a wide range of viruses. Although there has been significant research on zoonotic viruses in rodents, research on the diversity of other viruses has been limited, especially for rodents in the families Cricetidae and Heteromyidae. In fecal and liver samples of nine species of rodents, we identify 346 distinct circular DNA viral genomes. Of these, a large portion are circular, single-stranded DNA viruses in the families Anelloviridae (n = 3), Circoviridae (n = 5), Genomoviridae (n = 7), Microviridae (n = 297), Naryaviridae (n = 4), Vilyaviridae (n = 15) and in the phylum Cressdnaviricota (n = 13) that cannot be assigned established families. We also identified two large bacteriophages of 36 and 50 kb that are part of the class Caudoviricetes. Some of these viruses are clearly those that infect rodents, however, most of these likely infect various organisms associated with rodents, their environment or their diet.}, } @article {pmid37275867, year = {2023}, author = {Wang, M and Xie, X and Zhao, S and Ma, X and Wang, Z and Zhang, Y}, title = {Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1136343}, pmid = {37275867}, issn = {1664-3224}, abstract = {OBJECTIVE: Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS.

METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377.

RESULTS: Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data.

CONCLUSION: A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.}, } @article {pmid37275381, year = {2023}, author = {García-Mateo, S and Lanas, A}, title = {Editorial: Improving the gut microbiome: applications of fecal transplantation in disease.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1203448}, doi = {10.3389/fmed.2023.1203448}, pmid = {37275381}, issn = {2296-858X}, } @article {pmid37275140, year = {2023}, author = {Bao, Z and Wei, R and Zheng, X and Zhang, T and Bi, Y and Shen, S and Zou, P and Zhang, J and Yan, H and Li, MD and Yang, Z and Gao, H}, title = {Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1185993}, doi = {10.3389/fmicb.2023.1185993}, pmid = {37275140}, issn = {1664-302X}, abstract = {INTRODUCTION: Submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.

METHODS: Based on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.

RESULTS: By comparing total BA spectrum between SMHN (-) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (-) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.

DISCUSSION: Our study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.}, } @article {pmid37274526, year = {2023}, author = {Crump, JA and Nyirenda, TS and Kalonji, LM and Phoba, MF and Tack, B and Platts-Mills, JA and Gordon, MA and Kariuki, SM}, title = {Nontyphoidal Salmonella Invasive Disease: Challenges and Solutions.}, journal = {Open forum infectious diseases}, volume = {10}, number = {Suppl 1}, pages = {S32-S37}, pmid = {37274526}, issn = {2328-8957}, abstract = {Nontyphoidal Salmonella are a leading cause of community-onset bacteremia and other serious infections in sub-Saharan African countries where large studies indicate that they are an uncommon cause of moderate-to-severe diarrhea. Approximately 535 000 nontyphoidal Salmonella invasive disease illnesses and 77 500 deaths were estimated to occur in 2017; 422 000 (78.9%) illnesses and 66 500 (85.9%) deaths in countries in sub-Saharan Africa. Lineages of Salmonella enterica serovar Typhimurium sequence type (ST) 313 and lineages of Salmonella enterica serovar Enteritidis ST11 dominate as causes of invasive disease. A major reservoir for these specific strains outside of humans has not been identified to date. Human fecal shedding of such strains is common in areas where nontyphoidal Salmonella invasive disease incidence is high. The case-fatality ratio of nontyphoidal Salmonella invasive disease is approximately 15%. Early diagnosis and treatment are needed to avert fatal outcomes. Antimicrobial resistance, including multiple drug resistance, decreased fluoroquinolone susceptibility, and resistance to third-generation cephalosporins, is increasing in prevalence and is likely to further compromise patient outcomes. Naturally acquired immunity against invasive disease develops in children aged >3 years in endemic areas, likely mediated in part by the sequential acquisition of T-cell immunity, followed by antigen-specific immunoglobulin G antibodies. Vaccines in preclinical or clinical development include live-attenuated S. enterica serovar Typhimurium, nontyphoidal S. enterica core and O-polysaccharide glycoconjugates, multiple antigen-presenting system complexes, and generalized modules for membrane antigens vaccines. The latter are in phase I trials in Europe and Africa. Both vaccine use, and other effective, evidence-based nonvaccine interventions, are needed to prevent and control nontyphoidal Salmonella invasive disease.}, } @article {pmid37274301, year = {2023}, author = {Tariq, R and Pardi, DS and Khanna, S}, title = {Resolution rates in clinical trials for microbiota restoration for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231174293}, pmid = {37274301}, issn = {1756-283X}, abstract = {BACKGROUND: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower.

OBJECTIVES: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs).

DESIGN: A systematic review and meta-analysis was conducted.

DATA SOURCES AND METHODS: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs).

RESULTS: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71-85%). There was significant heterogeneity among studies with an I[2] of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60-82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p < 0.0001).

CONCLUSIONS: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies.}, } @article {pmid37272879, year = {2023}, author = {Huang, J and Zhou, H and Song, T and Wang, B and Ge, H and Zhang, D and Shen, P and Qiu, X and Li, H}, title = {Fecal microbiota transplantation from sodium alginate-dosed mice and normal mice mitigates intestinal barrier injury and gut dysbiosis induced by antibiotics and cyclophosphamide.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo01193c}, pmid = {37272879}, issn = {2042-650X}, abstract = {This study investigated the protective properties of fecal microbiota derived from mice treated with sodium alginate (SA) and normal mice with both types immunosuppressed by exposure to antibiotics and cyclophosphamide. A dietary intervention using SA obviously increased the diversity and improved the composition of gut microbiota in normal mice. Fecal microbiota transfer (FMT) from both mice treated with sodium alginate and normal mice alleviated spleen tissue damage and improved immune function. FMT alleviated intestinal mucosal injury and reduced intestinal permeability via increasing mucin and tight junction protein expression. In addition, FMT reduced gut inflammation via down-regulating the expression of toll-like receptor 4 protein. Furthermore, FMT treatment improved the disordered gut microbiota via increasing the abundance of Lactobacillus and Lachnospiraceae NK4A136 group whilst decreasing the abundance of Bacteroides. PICRUSt2 function prediction analysis showed that, compared with the model group, FMT treatment significantly down-regulated lipopolysaccharide biosynthesis and the mitogen-activated protein kinase signaling pathway-fly. Collectively, we found that SA can regulate the gut microbiota structure of normal mice and confirms the effectiveness of FMT in alleviating intestinal barrier damage and gut dysbiosis in antibiotic-cyclophosphamide-induced immunosuppressed mice. This work also reveals that SA can potentially alleviate the immunosuppression caused by cyclophosphamide in mice by modulating the intestinal microbiota and exploiting their functional properties.}, } @article {pmid37269894, year = {2023}, author = {Shaosan, Z and Zhao, T and Wang, Y and Mi, J and Liu, J and Fan, X and Niu, R and Sun, Z}, title = {Intestinal microbiota regulates colonic inflammation in fluorosis mice by TLR/NF-κB pathway through short-chain fatty acids.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {113866}, doi = {10.1016/j.fct.2023.113866}, pmid = {37269894}, issn = {1873-6351}, abstract = {Intestinal inflammation and microbial dysbiosis are found simultaneously in patients with fluorosis. However, whether the inflammation derived from fluoride exposure only or intestinal microbial disorders has not been clarified. In this study, 100 mg/L NaF exposure for 90 days significantly elevated the expressions of inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, and IL-10), and the levels of TLR4, TRAF6, Myd88, IKKβ, and NF-κB P65 in mouse colon, while the above factors were reduced in pseudo germ-free mice with fluorosis, hinting that disordered microbiota might play a more direct role in the development of colonic inflammation than fluoride. Fecal microbiota transplantation (FMT) lowered the levels of inflammatory factors and inactivated the TLR/NF-κB pathway in fluoride-exposed mice. In addition, supplementing short-chain fatty acids (SCFAs) exhibited the identical effects to the model of FMT. In summary, intestinal microbiota may alleviate the colonic inflammatory of mice with fluorosis by regulating TLR/NF-κB pathway through SCFAs.}, } @article {pmid37265903, year = {2023}, author = {Duhan, S and Keisham, B and Salim, A}, title = {Fulminant Clostridioides difficile Colitis With SARS-CoV-2 Infection.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e38401}, pmid = {37265903}, issn = {2168-8184}, abstract = {Clostridioides difficile (C. difficile)and coronavirus disease 2019 (COVID-19) infections can have overlapping symptoms. Recently, the association and outcomes of coinfection have been studied. We present the case of an 83-year-old lady with Parkinson's disease (PD) who was admitted with pneumonia secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. She was treated with empiric antibiotics ampicillin-sulbactam and azithromycin, along with antiviral therapy remdesivir and baricitinib, and dexamethasone. The patient developed severe C. difficile infection with a leukemoid reaction. She was treated with intravenous metronidazole and oral vancomycin without any improvement. Before she could receive a fecal microbiota transplant, her infection progressed to fulminant colitis, and she required emergent surgery. The patient developed several complications post-surgery and succumbed to the severe illness. Our patient's multiple comorbidities and an underlying COVID-19 infection predisposed her to severe illness. This case emphasizes the long-standing discussion on antibiotic stewardship and encourages a debate on the role of immunosuppressant antiviral medications and underlying PD in predisposing patients to a severe C. difficile infection.}, } @article {pmid37265797, year = {2023}, author = {Zha, C and Peng, Z and Huang, K and Tang, K and Wang, Q and Zhu, L and Che, B and Li, W and Xu, S and Huang, T and Yu, Y and Zhang, W}, title = {Potential role of gut microbiota in prostate cancer: immunity, metabolites, pathways of action?.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1196217}, pmid = {37265797}, issn = {2234-943X}, abstract = {The gut microbiota helps to reveal the relationship between diseases, but the role of gut microbiota in prostate cancer (PCa) is still unclear. Recent studies have found that the composition and abundance of specific gut microbiota are significantly different between PCa and non-PCa, and the gut microbiota may have common and unique characteristics between different diseases. Intestinal microorganisms are affected by various factors and interact with the host in a variety of ways. In the complex interaction model, the regulation of intestinal microbial metabolites and the host immune system is particularly important, and they play a key role in maintaining the ecological balance of intestinal microorganisms and metabolites. However, specific changes in the composition of intestinal microflora may promote intestinal mucosal immune imbalance, leading to the formation of tumors. Therefore, this review analyzes the immune regulation of intestinal flora and the production of metabolites, as well as their effects and mechanisms on tumors, and briefly summarizes that specific intestinal flora can play an indirect role in PCa through their metabolites, genes, immunity, and pharmacology, and directly participate in the occurrence, development, and treatment of tumors through bacterial and toxin translocation. We also discussed markers of high risk PCa for intestinal microbiota screening and the possibility of probiotic ingestion and fecal microbiota transplantation, in order to provide better treatment options for clinic patients. Finally, after summarizing a number of studies, we found that changes in immunity, metabolites.}, } @article {pmid37265220, year = {2023}, author = {Alhobayb, T and Ciorba, MA}, title = {Clostridium difficile in inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000000949}, pmid = {37265220}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients.

RECENT FINDINGS: CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children.

SUMMARY: Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.}, } @article {pmid37264259, year = {2023}, author = {Zurek-Leffers, FM and Lehmann, F and Brabenec, L and Kintrup, S and Hellenthal, KEM and Mersjann, K and Kneifel, F and Hessler, M and Arnemann, PH and Kampmeier, TG and Ertmer, C and Kellner, P and Wagner, NM}, title = {A model of porcine polymicrobial septic shock.}, journal = {Intensive care medicine experimental}, volume = {11}, number = {1}, pages = {31}, pmid = {37264259}, issn = {2197-425X}, abstract = {BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.

MATERIALS AND METHODS: The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.

RESULTS: Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.

CONCLUSIONS: We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.}, } @article {pmid37263544, year = {2023}, author = {Sumiyoshi, A and Fujii, H and Okuma, Y}, title = {Targeting microbiome, drug metabolism, and drug delivery in oncology.}, journal = {Advanced drug delivery reviews}, volume = {}, number = {}, pages = {114902}, doi = {10.1016/j.addr.2023.114902}, pmid = {37263544}, issn = {1872-8294}, abstract = {Recent emerging scientific evidence shows a relationship between gut microbiota (GM) and immunomodulation. In the recently published "Hallmarks of Cancer", the microbiome has been reported to play a crucial role in cancer research, and perspectives for its clinical implementation to improve the effectiveness of pharmacotherapy were explored. Several studies have shown that GM can affect the outcomes of pharmacotherapy in cancer, suggesting that GM may affect anti-tumor immunity. Thus, studies on GM that analyze big data using computer-based analytical methods are required. To deliver GM to an environment that favors the growth of immune cells inside and outside the tumor microenvironment (TME), several challenges need to be overcome for each delivery method (oral, endoscopic, and intravenous). Clinical trials are in progress to evaluate the effects of targeting GM and whether it can enhance immunity or act on the TME, thereby to improve the clinical outcomes for cancer patients.}, } @article {pmid37261348, year = {2023}, author = {Singh, A and Alexander, SG and Martin, S}, title = {Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1114499}, pmid = {37261348}, issn = {1664-3224}, abstract = {The gut microbiome has an impact on cancer immune surveillance and immunotherapy, with recent studies showing categorical differences between immunotherapy-sensitive and immunotherapy-resistant cancer patient cohorts. Although probiotics are traditionally being supplemented to promote treatments or sustain therapeutic benefits; the FDA has not approved any for use with immunotherapy. The first step in developing probiotics for immunotherapy is identifying helpful or harmful bacteria down to the strain level. The gut microbiome's heterogeneity before and during treatment is also being investigated to determine microbial strains that are important for immunotherapy. Moreover, Dietary fiber intake, prebiotic supplementation and fecal microbiota transplantation (FMT) were found to enhance intratumoral CD8+ T cell to T-reg ratio in the clinics. The possibility of probiotic immunotherapy as a "living adjuvant" to CAR treatment and checkpoint blockade resistance is actively being investigated.}, } @article {pmid37258604, year = {2023}, author = {Sugita, K and Shima, A and Takahashi, K and Ishihara, G and Kawano, K and Ohmori, K}, title = {Pilot evaluation of a single oral fecal microbiota transplantation for canine atopic dermatitis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8824}, pmid = {37258604}, issn = {2045-2322}, abstract = {The gut microbiota has been suggested to be involved in the pathogenesis of canine atopic dermatitis (cAD). However, the gut microbiota has not been well characterized in dogs with atopic dermatitis (AD). In addition, the efficacy of fecal microbiota transplantation (FMT) in dogs with AD remains unclear. This research, therefore, aimed to characterize the gut microbiota of dogs with AD and conduct pilot evaluation of the efficacy of a single oral FMT on clinical signs and the gut microbiota of dogs with AD. For these purposes, we used 12 dogs with AD and 20 healthy dogs. The 16S rRNA analysis of the fecal microbiota revealed significant differences between 12 dogs with AD and 20 healthy dogs. Next, a single oral FMT was performed in 12 dogs with AD as a single-arm, open-label clinical trial for 56 days. A single oral FMT significantly decreased Canine Atopic Dermatitis Extent and Severity Index (CADESI)-04 scores from day 0 (median score, 16.5) to day 56 (8) and Pruritus Visual Analog Scale (PVAS) scores from days 0 (median score, 3) to day 56 (1). Furthermore, a single oral FMT changed the composition of the fecal microbiota of dogs with AD at the phylum and genus levels. The number of common amplicon sequence variants in the fecal microbiota between donor dogs and dogs with AD was positively correlated with CADESI-04 and PVAS reduction ratios 56 days after FMT. Our findings suggest that the gut microbiota plays a pivotal role in the pathogenesis of cAD, and that oral FMT could be a new therapeutic approach targeting the gut microbiota in cAD.}, } @article {pmid37258543, year = {2023}, author = {Liu, J and Sun, J and Yu, J and Chen, H and Zhang, D and Zhang, T and Ma, Y and Zou, C and Zhang, Z and Ma, L and Yu, X}, title = {Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {29}, pmid = {37258543}, issn = {2055-5008}, abstract = {Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, had no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, was demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA in NAFLD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) confirmed the critical role of gut microbiota in OCA treatment for NAFLD by effectively alleviating histopathological lesions and restoring liver function impaired by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia muciniphila, Bifidobacterium spp., Bacteroides spp., Alistipes spp., Lactobacillus spp., Streptococcus thermophilus, and Parasutterella excrementihominis. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing levels of serum hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of serum-conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the HFD-fed mice. Strong correlations were observed between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched by OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) mainly responsible for primary bile acid deconjugation. In conclusion, this study demonstrated that OCA intervention altered gut microbiota composition with specially enriched gut microbes modulating host bile acids, thus effectively alleviating NAFLD in the mice.}, } @article {pmid37257477, year = {2023}, author = {Schönherr, S and Jung, L and Lübbert, C}, title = {[Clostridioides difficile - New Insights and Therapy Recommendations].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {148}, number = {12}, pages = {752-758}, doi = {10.1055/a-1970-9211}, pmid = {37257477}, issn = {1439-4413}, abstract = {After an increase in Clostridioides difficile infections (CDI) until 2013 due to epidemic ribotypes such as 027 and 078, CDI incidence in Germany is now declining, as confirmed by recent epidemiological data. Despite this success through antimicrobial stewardship and hospital hygiene, the burden of disease remains high, especially in older patients (>65 years) with comorbidities. The main risk factor for CDI is the use of broad-spectrum antibiotics, which disrupt the gut microbiota, allowing C. difficile colonization. Coinfection with other intestinal pathogens such as enterococci can further increase the virulence of C. difficile. The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate. Vancomycin remains a good alternative; however, metronidazole should only be used if neither antibiotic is available. In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial.}, } @article {pmid37256150, year = {2023}, author = {Ben-Azu, B and Del Re, EC and VanderZwaag, J and Carrier, M and Keshavan, M and Khakpour, M and Tremblay, MÈ}, title = {Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1139357}, pmid = {37256150}, issn = {1662-5102}, abstract = {Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.}, } @article {pmid37255721, year = {2023}, author = {Solanki, R and Karande, A and Ranganathan, P}, title = {Emerging role of gut microbiota dysbiosis in neuroinflammation and neurodegeneration.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1149618}, pmid = {37255721}, issn = {1664-2295}, abstract = {Alzheimer's disease (AD), is a chronic age-related progressive neurodegenerative disorder, characterized by neuroinflammation and extracellular aggregation of Aβ peptide. Alzheimer's affects every 1 in 14 individuals aged 65 years and above. Recent studies suggest that the intestinal microbiota plays a crucial role in modulating neuro-inflammation which in turn influences Aβ deposition. The gut and the brain interact with each other through the nervous system and chemical means via the blood-brain barrier, which is termed the Microbiota Gut Brain Axis (MGBA). It is suggested that the gut microbiota can impact the host's health, and numerous factors, such as nutrition, pharmacological interventions, lifestyle, and geographic location, can alter the gut microbiota composition. Although, the exact relationship between gut dysbiosis and AD is still elusive, several mechanisms have been proposed as drivers of gut dysbiosis and their implications in AD pathology, which include, action of bacteria that produce bacterial amyloids and lipopolysaccharides causing macrophage dysfunction leading to increased gut permeability, hyperimmune activation of inflammatory cytokines (IL-1β, IL-6, IL-8, and NLRP3), impairment of gut- blood brain barrier causing deposition of Aβ in the brain, etc. The study of micro-organisms associated with dysbiosis in AD with the aid of appropriate model organisms has recognized the phyla Bacteroidetes and Firmicutes which contain organisms of the genus Escherichia, Lactobacillus, Clostridium, etc., to contribute significantly to AD pathology. Modulating the gut microbiota by various means, such as the use of prebiotics, probiotics, antibiotics or fecal matter transplantation, is thought to be a potential therapeutic intervention for the treatment of AD. This review aims to summarize our current knowledge on possible mechanisms of gut microbiota dysbiosis, the role of gut brain microbiota axis in neuroinflammation, and the application of novel targeted therapeutic approaches that modulate the gut microbiota in treatment of AD.}, } @article {pmid37253485, year = {2023}, author = {Chen, L and Guo, L and Feng, S and Wang, C and Cui, Z and Wang, S and Lu, Q and Chang, H and Hang, B and Snijders, AM and Mao, JH and Lu, Y and Ding, D}, title = {Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice.}, journal = {BMJ open diabetes research & care}, volume = {11}, number = {3}, pages = {}, doi = {10.1136/bmjdrc-2022-003282}, pmid = {37253485}, issn = {2052-4897}, abstract = {INTRODUCTION: Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated.

RESEARCH DESIGN AND METHODS: Eight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4 weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing.

RESULTS: Our results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells.

CONCLUSIONS: FMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.}, } @article {pmid37252544, year = {2023}, author = {Malik, H and Malik, H and Uderani, M and Berhanu, M and Soto, CJ and Saleem, F}, title = {Fulminant Hepatitis A and E Co-infection Leading to Acute Liver Failure: A Case Report.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e38101}, pmid = {37252544}, issn = {2168-8184}, abstract = {Acute liver failure (ALF) is a severe clinical condition with a high mortality rate. Although several factors can cause ALF, viral hepatitis remains one of the leading causes. Hepatitis A virus (HAV) and hepatitis E virus (HEV), which typically cause self-limiting acute disease, are rare but emerging causes of ALF, especially when both viruses infect the same individual. Both of these hepatotropic viruses share an enteric route and are most commonly transmitted through the fecal-oral route. The impact of HAV/HEV co-infection on acute hepatitis prognosis is not entirely understood, but dual infection can further exacerbate liver damage, leading to fulminant hepatic failure (FHF) with a higher mortality rate than a single virus infection. Here, we present a case of a 32-year-old male with no prior liver disease who presented to the emergency department with a two-week history of jaundice, abdominal pain, and hepatomegaly. Upon admission, he was disoriented with grade 2 encephalopathy. After a thorough investigation, co-infection with hepatitis A and E was identified as the primary cause of his ALF. The patient underwent intensive medical treatment and interventions, including dialysis. Unfortunately, the patient's survival was not possible due to the absence of availability of a transplanted organ, which is currently the only definitive treatment option. This case report underscores the significance of prompt diagnosis, timely intervention, and the accessibility of transplantation in the survival of liver failure, as it remains the sole definitive treatment for acute liver failure. Moreover, it provides a concise overview of the current literature on fulminant co-infection of HAV and HEV, including epidemiology, clinical characteristics, pathogenesis, diagnosis, treatment, and risk factors associated with co-infection of hepatitis A and E and their role in causing ALF. It also highlights the significance of identifying high-risk populations and implementing appropriate prevention and control measures such as vaccination, practising good hygiene and sanitation, and avoiding the consumption of contaminated food and water.}, } @article {pmid37249910, year = {2023}, author = {Margolis, EB and Alfaro, GM and Sun, Y and Dallas, RH and Allison, KJ and Ferrolino, J and Ross, HS and Davis, AE and Jia, Q and Turner, P and Mackay, V and Morin, CE and Triplett, BM and Klein, EJ and Englund, JA and Tang, L and Hayden, RT}, title = {Microbiota Predict Infections and Acute Graft-Versus-Host Disease after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiad190}, pmid = {37249910}, issn = {1537-6613}, abstract = {BACKGROUND: Despite intensive prophylactic and pre-emptive measures, infections remain an important cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Disruption of the gut microbiota has been linked to clinical outcomes after adult allo-HCT. This study evaluated whether these or differing microbiota disruptions or signatures were associated with risk of infection in pediatric allo-HCT.

METHODS: In a prospective observational study, fecal samples from 74 children were collected prior to conditioning and at the time of neutrophil recovery and profiled by means of 16S ribosomal rRNA sequencing. The associations between microbiome signatures and infections or acute graft-versus-host disease (aGVHD) were examined using Cox proportional-hazards analysis.

RESULTS: Previously associated indices of microbiome disruption in adults, including diversity and butyrate producer frequency, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (e.g. Lachnoclostridium, Parabacteroides, Clostridium spp.) prior to conditioning predicted likelihood of bacteremia (cox hazards ratio 3.89) in first year post HCT. A distinct ratio of oral (e.g. Rothia, Veillonella spp.) to colonic anaerobes (e.g. Anaerobutyricum, Dorea, Romboutsia spp.) at neutrophil recovery predicted likelihood of bacterial infections (cox hazards ratio 1.81) and viral enterocolitis (cox hazards ratio 1.96) through first year post transplant.

CONCLUSIONS: Interactions between medical interventions, pediatric hosts and microbial communities may be responsible for these consistent microbiota signatures that predict infections. A future multi-center investigation will be needed to demonstrate whether these ratios can be generalized to other pediatric cohorts.}, } @article {pmid37249187, year = {2023}, author = {Horesh, N and Emile, SH and Khan, SM and Freund, MR and Garoufalia, Z and Silva-Alvarenga, E and Gefen, R and Wexner, SD}, title = {Meta-Analysis of Randomized Clinical Trials on Long-Term Outcomes of Surgical Treatment of Perforated Diverticulitis.}, journal = {Annals of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/SLA.0000000000005909}, pmid = {37249187}, issn = {1528-1140}, abstract = {OBJECTIVE: Assess long-term outcomes of patients with perforated diverticulitis treated with resection or laparoscopic lavage (LL).

SUMMARY BACKGROUND DATA: Surgical treatment of perforated diverticulitis changed in the last few decades. LL and increasing evidence that primary anastomosis (PRA) is feasible in certain patients have broadened surgical options. However, debate for the optimal surgical strategy lingers.

METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials (RCT) on surgical treatment of perforated diverticulitis from inception to October 2022. Long-term reports of RCT comparing surgical interventions for treatment of perforated diverticulitis were selected. Main outcomes measures were long-term ostomy, long term complications, recurrence, and re-intervention rates.

RESULTS: After screening 2431 studies, 5 long-term follow-up studies of RCT comprising 499 patients were included. Three studies, excluding patients with fecal peritonitis, compared LL and colonic resection, two compared PRA and Hartmann's procedure. LL had lower odds of long-term ostomy (OR= 0.133, 95%CI: 0.278- 0.579;P<0.001) and re-operation (OR= 0.585, 95%CI: 0.365- 0.937;P=0.02) compared to colonic resection but higher odds of diverticular disease recurrence (OR= 5.8, 95%CI: 2.33- 14.42;P<0.001). Colonic resection with PRA had lower odds of long-term ostomy (OR= 0.02, 95%CI: 0.003-0.195;P<0.001), long-term complications (OR= 0.195, 95%CI: 0.113-0.335;P<0.001), reoperation (OR= 0.2, 95%CI: 0.108- 0.384;P<0.001) and incisional hernia (OR= 0.184, 95%CI: 0.102-0.333;P<0.001). There was no significant difference in odds of mortality among the procedures.

CONCLUSIONS: Long-term follow-up of patients who underwent emergency surgery for perforated diverticulitis showed that LL had lower odds of long-term ostomy and re-operation, but more risk for disease recurrence when compared to resection in purulent peritonitis. Colonic resection with PRA had better long-term outcomes than Hartmann's procedure for fecal peritonitis.}, } @article {pmid37247177, year = {2023}, author = {Mohan, BP and Loganathan, P and Khan, SR and Garg, G and Muthusamy, A and Ponnada, S and Pasam, RT and Chandan, S and Tuteja, A}, title = {Fecal microbiota transplant delivered via invasive routes in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {37247177}, issn = {0975-0711}, abstract = {BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) results in significant loss of quality of life. Management guidelines do not recommend fecal microbiota transplant (FMT) for IBS based on weak evidence as refined data is lacking. We performed a systematic review and meta-analysis to ascertain the pooled clinical outcomes of FMT in IBS, delivered via invasive routes.

METHODS: Multiple databases were searched through January 2023 to identify studies that reported on FMT treatment in IBS by invasive routes. Standard meta-analysis methodology using the random-effects model was used. Heterogeneity was assessed by I[2]% and 95% predication interval.

RESULTS: Five studies were included. As many as 377 IBS patients were assessed, of which 238 received FMT and 139 received placebo. One study used nasojejunal tubes, one esophagogastroduodenoscopy and three colonoscopy for FMT delivery. FMT via colonoscopy was performed as a one-time procedure instilled into the cecum. Two studies used 30 g of stool from a single universal donor and one study used 50-80 g of pooled donor feces. The pooled odds ratio of improvement in IBS symptoms with FMT was significantly better as compared to that of placebo OR = 2.9 (95% CI [1.6-5.2, I[2] = 62%, p < 0.001]). This was true for studies that exclusively used colonoscopy (OR = 2.1 [1.1-4.2, p = 0.04]). In the FMT arm, 10 patients (10.6%) reported abdomen pain and worsening of symptoms with bloating and six patients (6.3%) reported diarrhea.

CONCLUSION: FMT delivered via invasive routes, especially colonoscopy, demonstrated significant improvement in IBS symptoms. A single FMT consisting of 30 g or more of single universal donor feces instilled into the cecum is the predominant modality.}, } @article {pmid37247104, year = {2023}, author = {Ganji, N and Li, B and Lee, C and Pierro, A}, title = {Necrotizing enterocolitis: recent advances in treatment with translational potential.}, journal = {Pediatric surgery international}, volume = {39}, number = {1}, pages = {205}, pmid = {37247104}, issn = {1437-9813}, support = {353857/CAPMC/CIHR/Canada ; }, abstract = {Necrotizing enterocolitis (NEC) is one of the most prevalent and devastating gastrointestinal disorders in neonates. Despite advances in neonatal care, the incidence and mortality due to NEC remain high, highlighting the need to devise novel treatments for this disease. There have been a number of recent advancements in therapeutic approaches for the treatment of NEC; these involve remote ischemic conditioning (RIC), stem cell therapy, breast milk components (human milk oligosaccharides, exosomes, lactoferrin), fecal microbiota transplantation, and immunotherapy. This review summarizes the most recent advances in NEC treatment currently underway as well as their applicability and associated challenges and limitations, with the aim to provide new insight into the paradigm of care for NEC worldwide.}, } @article {pmid37246923, year = {2023}, author = {El-Salhy, M}, title = {Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14621}, doi = {10.1111/nmo.14621}, pmid = {37246923}, issn = {1365-2982}, abstract = {The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the pathophysiology of IBS. This narrative review was designed to present recent observations made relating to fecal microbiota transplantation (FMT), which implicate possible roles of 11 intestinal bacteria in the pathophysiology of IBS. The intestinal abundances of nine of these bacteria increased after FMT in patients with IBS, and these increases were inversely correlated with IBS symptoms and fatigue severity. These bacteria were Alistipes spp., Faecalibacterium prausnitzii, Eubacterium biforme, Holdemanella biformis, Prevotella spp., Bacteroides stercoris, Parabacteroides johnsonii, Bacteroides zoogleoformans, and Lactobacillus spp. The intestinal abundances of two bacteria were decreased in patients with IBS after FMT and were correlated with the severity of IBS symptoms and fatigue (Streptococcus thermophilus and Coprobacillus cateniformis). Ten of these bacteria are anaerobic and one (Streptococcus thermophilus) is facultative anaerobic. Several of these bacteria produce short-chain fatty acids, especially butyrate, which is used as an energy source by large intestine epithelial cells. Moreover, it modulates the immune response and hypersensitivity of the large intestine and decreases intestinal cell permeability and intestinal motility. These bacteria could be used as probiotics to improve these conditions. Protein-rich diets could increase the intestinal abundance of Alistipes, and plant-rich diet could increase the intestinal abundance of Prevotella spp., and consequently improve IBS and fatigue.}, } @article {pmid37246133, year = {2023}, author = {Wu, R and Xiong, R and Li, Y and Chen, J and Yan, R}, title = {Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103062}, doi = {10.1016/j.jaut.2023.103062}, pmid = {37246133}, issn = {1095-9157}, abstract = {Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.}, } @article {pmid37245237, year = {2023}, author = {Li, DS and Wu, YR and Du, WH and Zhu, YL and Zhang, WJ and Fu, Y and Yang, GB}, title = {The composition of the intestinal microbiota after allogeneic haematopoietic stem cell translantation and its association with graft versus host disease as assessed by 16Sribosomal ribonucleic acid.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {74}, number = {1}, pages = {}, doi = {10.26402/jpp.2023.1.10}, pmid = {37245237}, issn = {1899-1505}, abstract = {To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.}, } @article {pmid37245211, year = {2023}, author = {Alves, JC and Santos, A and Jorge, P and Pitães, Â}, title = {Faecal microbiome transplantation improves clinical signs of chronic idiopathic large bowel diarrhoea in working dogs.}, journal = {The Veterinary record}, volume = {}, number = {}, pages = {e3052}, doi = {10.1002/vetr.3052}, pmid = {37245211}, issn = {2042-7670}, abstract = {BACKGROUND: Chronic diarrhoea is a common clinical sign in dogs with chronic enteropathy, and psyllium husk has been shown to improve clinical signs in affected dogs. The aim of this study was to investigate whether faecal microbiome transplant has a similar effect in alleviating clinical signs in dogs with chronic large bowel diarrhoea.

METHOD: Thirty large-breed working dogs with chronic large bowel diarrhoea were divided into a psyllium group (PG) and a faecal microbiome transplant group (FMTG). To the PG, 16 g/day of psyllium husk was administered for 30 days. The FMTG received faecal microbiome transplantation (FMT) once via enema. A daily log of faecal characteristics was kept, and the dogs' canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were determined. A Wilcoxon-Mann-Whitney test was used to compare group results. In addition, the Kaplan-Meier test was used to evaluate the occurrence rate of 1 day or more of diarrhoea and 2 days or more of diarrhoea by day 30.

RESULTS: The sample had a mean age of 3.9 ± 2.1 years and a bodyweight of 25.3 ± 6.8 kg. The FMTG showed a more rapid onset of CIBDAI improvement but no difference in other measures. At 30 days, the FMTG showed a greater improvement in bodyweight and BCS, but no differences were observed in faecal scores, defaecation frequency and time of appearance of episodes of diarrhoea. Time played a significant positive role in the results observed across both groups (p < 0.05).

LIMITATIONS: This study did not compare the microbiomes of the dogs before and after treatment, so the role of specific types of bacteria cannot be determined.

CONCLUSION: Psyllium husk and FMT had similar effects in improving clinical signs of chronic large bowel diarrhoea.}, } @article {pmid37232579, year = {2023}, author = {Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis.}, journal = {Clinical and translational gastroenterology}, volume = {14}, number = {5}, pages = {e00568}, pmid = {37232579}, issn = {2155-384X}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Remission Induction ; }, abstract = {INTRODUCTION: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation.

METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach.

RESULTS: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models.

DISCUSSION: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.}, } @article {pmid37244385, year = {2023}, author = {Wang, L and Zhang, K and Zeng, Y and Luo, Y and Peng, J and Zhang, J and Kuang, T and Fan, G}, title = {Gut mycobiome and metabolic diseases: The known, the unknown, and the future.}, journal = {Pharmacological research}, volume = {193}, number = {}, pages = {106807}, doi = {10.1016/j.phrs.2023.106807}, pmid = {37244385}, issn = {1096-1186}, abstract = {Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide. In recent years, most research on the role of gut microbes in metabolic diseases has focused on bacteria, whereas fungal microbes have been neglected. This review aims to provide a comprehensive overview of gut fungal alterations in T2DM, obesity, and NAFLD, and to discuss the mechanisms associated with disease development. In addition, several novel strategies targeting gut mycobiome and/or their metabolites to improve T2DM, obesity and NAFLD, including fungal probiotics, antifungal drugs, dietary intervention, and fecal microbiota transplantation, are critically discussed. The accumulated evidence suggests that gut mycobiome plays an important role in the occurrence and development of metabolic diseases. The possible mechanisms by which the gut mycobiome affects metabolic diseases include fungal-induced immune responses, fungal-bacterial interactions, and fungal-derived metabolites. Candida albicans, Aspergillus and Meyerozyma may be potential pathogens of metabolic diseases because they can activate the immune system and/or produce harmful metabolites. Moreover, Saccharomyces boulardii, S. cerevisiae, Alternaria, and Cochliobolus fungi may have the potential to improve metabolic diseases. The information may provide an important reference for the development of new therapeutics for metabolic diseases based on gut mycobiome.}, } @article {pmid37243505, year = {2023}, author = {Bruggeling, CE and Te Groen, M and Garza, DR and van Heeckeren Tot Overlaer, F and Krekels, JPM and Sulaiman, BC and Karel, D and Rulof, A and Schaaphok, AR and Hornikx, DLAH and Nagtegaal, ID and Dutilh, BE and Hoentjen, F and Boleij, A}, title = {Bacterial oncotraits rather than spatial organization are associated with dysplasia in ulcerative colitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjad092}, pmid = {37243505}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Colonic bacterial biofilms are frequently present in ulcerative colitis (UC) and may increase dysplasia risk through pathogens expressing oncotraits. This prospective cohort study aimed to determine (1) the association of oncotraits and longitudinal biofilm presence with dysplasia risk in UC, and (2) the relation of bacterial composition with biofilms and dysplasia risk.

METHODS: Feces and left- and right-sided colonic biopsies were collected from 80 UC patients and 35 controls. Oncotraits (FadA of Fusobacterium, BFT of Bacteroides fragilis, colibactin (ClbB) and Intimin (Eae) of Escherichia coli) were assessed in fecal DNA with multiplex qPCR. Biopsies were screened for biofilms (n=873) with 16S rRNA fluorescent in situ hybridization. Shotgun metagenomic sequencing (n=265), and ki67-immunohistochemistry were performed. Associations were determined with a mixed-effects regression model.

RESULTS: Biofilms were highly prevalent in UC patients (90.8%) with a median persistence of 3 years (IQR 2-5 years). Biofilm-positive biopsies showed increased epithelial hypertrophy (p=0.025), a reduced Shannon diversity independent of disease status (p=0.015), however, were not significantly associated with dysplasia in UC (aOR 1.45(95%CI0.63-3.40). In contrast, ClbB independently associated with dysplasia (aOR 7.16 (95%CI1.75-29.28), while FadA and Fusobacteriales were associated with a decreased dysplasia risk in UC (aOR 0.23 (95%CI0.06-0.83), and p<0.01).

CONCLUSIONS: Biofilms are a hallmark of UC, however, because of their high prevalence a poor biomarker for dysplasia. In contrast, colibactin presence and FadA absence independently associate with dysplasia in UC and might therefore be valuable biomarkers for future risk stratification and intervention strategies.}, } @article {pmid37243442, year = {2023}, author = {Marasco, G and Buttitta, F and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {The role of microbiota and its modulation in colonic diverticular disease.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14615}, doi = {10.1111/nmo.14615}, pmid = {37243442}, issn = {1365-2982}, abstract = {BACKGROUND: Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria-driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro-inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions.

PURPOSE: Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies.}, } @article {pmid37241738, year = {2023}, author = {Huang, Y and Ying, N and Zhao, Q and Chen, J and Teow, SY and Dong, W and Lin, M and Jiang, L and Zheng, H}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed Mice following Fecal Microbiota Transplantation from Inulin-Dosed Mice.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {10}, pages = {}, doi = {10.3390/molecules28103997}, pmid = {37241738}, issn = {1420-3049}, abstract = {The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.}, } @article {pmid37240769, year = {2023}, author = {Keathley, J and White, J and Reid, G}, title = {The Impact of Nutrition, Physical Activity, Beneficial Microbes, and Fecal Microbiota Transplant for Improving Health.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, doi = {10.3390/life13051124}, pmid = {37240769}, issn = {2075-1729}, abstract = {The recognition that microbes are integral to human life has led to studies on how to manipulate them in favor of health outcomes. To date, there has been no conjoint recommendation for the intake of dietary compounds that can complement the ingested organisms in terms of promoting an improved health outcome. The aim of this review is to discuss how beneficial microbes in the form of probiotics, fermented foods, and donor feces are being used to manage health. In addition, we explore the rationale for selecting beneficial microbial strains and aligning diets to accommodate their propagation in the gut. A pilot clinical trial design is presented to examine the effects of probiotics and exercise in patients with phenylketonuria (PKU); it is the most common inborn error of amino acid metabolism, and it is a complication that requires lifelong dietary intervention. The example design is provided to illustrate the importance of using omics technology to see if the intervention elevates neuroactive biogenic amines in the plasma; increases the abundance of Eubacterium rectale, Coprococcus eutactus, Akkermansia muciniphila, or Butyricicoccus; and increases Escherichia/Shigella in the gut, all as markers of improved health. By emphasizing the combined importance of diet, microbial supplements, and the gut microbiome, we hope that future studies will better align these components, not only to improve outcomes, but also to enhance our understanding of the mechanisms.}, } @article {pmid37238943, year = {2023}, author = {Shahbazi, A and Sepehrinezhad, A and Vahdani, E and Jamali, R and Ghasempour, M and Massoudian, S and Sahab Negah, S and Larsen, FS}, title = {Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/biomedicines11051272}, pmid = {37238943}, issn = {2227-9059}, abstract = {A common neuropsychiatric complication of advanced liver disease, hepatic encephalopathy (HE), impacts the quality of life and length of hospital stays. There is new evidence that gut microbiota plays a significant role in brain development and cerebral homeostasis. Microbiota metabolites are providing a new avenue of therapeutic options for several neurological-related disorders. For instance, the gut microbiota composition and blood-brain barrier (BBB) integrity are altered in HE in a variety of clinical and experimental studies. Furthermore, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have been shown to positively affect BBB integrity in disease models that are potentially extendable to HE by targeting gut microbiota. However, the mechanisms that underlie microbiota dysbiosis and its effects on the BBB are still unclear in HE. To this end, the aim of this review was to summarize the clinical and experimental evidence of gut dysbiosis and BBB disruption in HE and a possible mechanism.}, } @article {pmid37237771, year = {2023}, author = {Airola, C and Severino, A and Porcari, S and Fusco, W and Mullish, BH and Gasbarrini, A and Cammarota, G and Ponziani, FR and Ianiro, G}, title = {Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, doi = {10.3390/antibiotics12050868}, pmid = {37237771}, issn = {2079-6382}, abstract = {The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.}, } @article {pmid37237476, year = {2023}, author = {Pezzino, S and Sofia, M and Mazzone, C and Castorina, S and Puleo, S and Barchitta, M and Agodi, A and Gallo, L and La Greca, G and Latteri, S}, title = {Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database.}, journal = {Biology}, volume = {12}, number = {5}, pages = {}, doi = {10.3390/biology12050662}, pmid = {37237476}, issn = {2079-7737}, abstract = {There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention. The purpose of this bibliometric analysis is to assess recent publishing trends concerning the role of the gut microbiome in the progression of NAFLD, NASH and cirrhosis and its connection with biotics. The free access version of the Dimensions scientific research database was used to find publications in this field from 2002 to 2022. VOSviewer and Dimensions' integrated tools were used to analyze current research trends. Research into the following topics is expected to emerge in this field: (1) evaluation of risk factors which are correlated with the progression of NAFLD, such as obesity and metabolic syndrome; (2) pathogenic mechanisms, such as liver inflammation through toll-like receptors activation, or alteration of short-chain fatty acids metabolisms, which contribute to NAFLD development and its progression in more severe forms, such as cirrhosis; (3) therapy for cirrhosis through dysbiosis reduction, and research on hepatic encephalopathy a common consequence of cirrhosis; (4) evaluation of diversity, and composition of gut microbiome under NAFLD, and as it varies under NASH and cirrhosis by rRNA gene sequencing, a tool which can also be used for the development of new probiotics and explore into the impact of biotics on the gut microbiome; (5) treatments to reduce dysbiosis with new probiotics, such as Akkermansia, or with fecal microbiome transplantation.}, } @article {pmid37235836, year = {2023}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2202366}, doi = {10.1200/JCO.22.02366}, pmid = {37235836}, issn = {1527-7755}, abstract = {PURPOSE: Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial.

METHODS: Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months.

RESULTS: In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister.

CONCLUSION: In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.}, } @article {pmid37235073, year = {2023}, author = {Nagarakanti, S and Orenstein, R}, title = {Treating Clostridioides difficile: Could Microbiota-based Live Biotherapeutic Products Provide the Answer?.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {3137-3143}, pmid = {37235073}, issn = {1178-6973}, abstract = {Clostridioides difficile infection (CDI) is a pressing health care issue due to the limited effectiveness of current treatments and high recurrence rates. Current available antibiotic options for CDI disrupt the fecal microbiome which predisposes recurrent CDI. Fecal microbiota transplantation (FMT) has improved the outcomes of recurrent CDI, but concerns surrounding the safety and standardization of the product persist. Microbiota-based live biotherapeutic products (LBPs), are emerging as potential alternatives to FMT for CDI treatment. This review explores the potential of LBPs as safe and effective therapy for CDI. While preclinical and early clinical studies have shown promising results, further research is necessary to determine the optimal composition and dosage of LBPs and to ensure their safety and efficacy in clinical practice. Overall, LBPs hold great promise as a novel therapy for CDI and warrant further investigation in other conditions related to disruption of the colonic microbiota.}, } @article {pmid37234168, year = {2023}, author = {Yang, Y and He, J and Wang, Y and Liang, L and Zhang, Z and Tan, X and Tao, S and Wu, Z and Dong, M and Zheng, J and Zhang, H and Feng, S and Cheng, W and Chen, Q and Wei, H}, title = {Whole intestinal microbiota transplantation is more effective than fecal microbiota transplantation in reducing the susceptibility of DSS-induced germ-free mice colitis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1143526}, pmid = {37234168}, issn = {1664-3224}, abstract = {Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of inflammatory bowel disease (IBD). Previous studies have reported that compared with FMT, whole intestinal microbiota transplantation (WIMT) can more precisely replicate the community structure and reduce the inflammatory response of the host. However, it remains unclear whether WIMT is more effective in alleviating IBD. To examine the efficacy of WIMT and FMT in the intervention of IBD, GF (Germ-free) BALB/c mice were pre-colonized with whole intestinal microbiota or fecal microbiota before being treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by both WIMT and FMT, as demonstrated by the prevention of body weight loss and decreased the Disease activity index and histological scores in mice. However, WIMT's anti-inflammatory effect was superior to that of FMT. In addition, the inflammatory markers myeloperoxidase (MPO) and eosinophil peroxidase were dramatically downregulated by WIMT and FMT. Furthermore, the use of two different types of donors facilitated the regulation of cytokine homeostasis in colitis mice; the level of the pro-inflammatory cytokine IL-1β in the WIMT group was significantly lower than that in the FMT group, while the level of the anti-inflammatory factor IL-10 was significantly higher than that in the FMT group. Both groups showed enhanced expression of occludin to protect the intestinal barrier in comparison with the DSS group, and the WIMT group demonstrated considerably increased levels of ZO-1. The sequencing results showed that the WIMT group was highly enriched in Bifidobacterium, whereas the FMT group was significantly enriched in Lactobacillus and Ochrobactrum. Correlation analysis revealed that Bifidobacterium was negatively correlated with TNF-α, whereas Ochrobactrum was positively correlated with MPO and negatively correlated with IL-10, which might be related to different efficacies. Functional prediction using PICRUSt2 revealed that the FMT group was considerably enriched in the L-arginine biosynthesis I and L-arginine biosynthesis IV pathway, whereas the WIMT group was enriched in the L-lysine fermentation to acetate and butanoate pathway. In conclusion, the symptoms of colitis were subsided to varying degrees by the two different types of donors, with the WIMT group being more effective than the FMT group. This study provides new information on clinical interventions for IBD.}, } @article {pmid37231259, year = {2023}, author = {Pinto, Y and Chakraborty, M and Jain, N and Bhatt, AS}, title = {Phage-inclusive profiling of human gut microbiomes with Phanta.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {37231259}, issn = {1546-1696}, abstract = {Due to technical limitations, most gut microbiome studies have focused on prokaryotes, overlooking viruses. Phanta, a virome-inclusive gut microbiome profiling tool, overcomes the limitations of assembly-based viral profiling methods by using customized k-mer-based classification tools and incorporating recently published catalogs of gut viral genomes. Phanta's optimizations consider the small genome size of viruses, sequence homology with prokaryotes and interactions with other gut microbes. Extensive testing of Phanta on simulated data demonstrates that it quickly and accurately quantifies prokaryotes and viruses. When applied to 245 fecal metagenomes from healthy adults, Phanta identifies ~200 viral species per sample, ~5× more than standard assembly-based methods. We observe a ~2:1 ratio between DNA viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. In another cohort, we observe that Phanta performs equally well on bulk versus virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis.}, } @article {pmid37230956, year = {2023}, author = {Song, Y and Cui, YB and Wang, YM and Yu, J and Wang, BL and Wen, QY and Zheng, X}, title = {Donor selection for fecal bacterial transplantation and its combined effects with inulin on early growth and ileal development in chicks.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxad099}, pmid = {37230956}, issn = {1365-2672}, abstract = {AIMS: To select the best donor and investigate its combined effects with inulin on growth performance, and ileal health of chicks.

METHODS AND RESULTS: The chicks (Hy-line Brown) were treated with fecal microbiota suspension from different breeder hens to select the best donor. Treatment with fecal microbiota transplantation (FMT) alone or in combination with inulin found that it improved gut microbiome in chicks. The organ indexes were increased on 7d, especially the bursa of fabricius index (P < 0.05). On 14d, immune performance, ileal morphology, and barrier were improved, simultaneously, the concentration of short-chain fatty acids was also increased. In addition, for the expression of ileal barrier-related genes, Anaerofustis and Clostridium were positively correlated with them (P < 0.05), Blautia, Prevotella, Veillonella, and Weissella were the opposite (P < 0.05), and RFN20 showed a positive correlation with gut morphology (P < 0.05).

CONCLUSION: Combination of homologous FMT and inulin promoted early growth and intestinal health of chicks.}, } @article {pmid37229456, year = {2023}, author = {Wu, J and Yang, K and Fan, H and Wei, M and Xiong, Q}, title = {Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1114424}, pmid = {37229456}, issn = {1664-2392}, abstract = {Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.}, } @article {pmid37229259, year = {2023}, author = {Li, HJ and Li, DQ and Zhang, YL and Ding, XF and Gao, HT and Zhu, Y and Liu, J and Zhang, LX and Chen, J and Chen, G and Yu, Y}, title = {Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1123387}, doi = {10.3389/fphar.2023.1123387}, pmid = {37229259}, issn = {1663-9812}, abstract = {Gut microbiota affects the gut-brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers-TNF-α, IL-1β, IL-6, and iNOS-in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.}, } @article {pmid37228365, year = {2023}, author = {Wang, R}, title = {Clostridioides difficile infection: microbe-microbe interactions and live biotherapeutics.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1182612}, doi = {10.3389/fmicb.2023.1182612}, pmid = {37228365}, issn = {1664-302X}, abstract = {Clostridioides difficile is a gram-positive, spore-forming, obligate anaerobe that infects the colon. C. difficile is estimated to cause nearly half a million cases in the United States annually, with about 29,000 associated deaths. Unfortunately, the current antibiotic treatment is not ideal. While antibiotics can treat the infections, they also disrupt the gut microbiota that mediates colonization resistance against enteric pathogens, including C. difficile; disrupted gut microbiota provides a window of opportunity for recurrent infections. Therefore, therapeutics that restore the gut microbiota and suppress C. difficile are being evaluated for safety and efficacy. This review will start with mechanisms by which gut bacteria affect C. difficile pathogenesis, followed by a discussion on biotherapeutics for recurrent C. difficile infections.}, } @article {pmid37227445, year = {2023}, author = {Luo, Q and Gong, P and Shi, R and Chen, W and Wang, C and Zhang, C and Wu, Z}, title = {Syringic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c02441}, pmid = {37227445}, issn = {1520-5118}, abstract = {Inflammatory bowel disease is known to be associated with alterations in gut microbiota. The bioactive compound syringic acid has been shown to alleviate inflammatory bowel disease, but its interaction with gut microbiota and mechanism of action remain unclear. To address this, we conducted a study in which we investigated the potential benefits of syringic acid in a mouse model of dextran sulfate sodium-induced colitis through gut microbiota modulation. Our results show that oral administration of syringic acid effectively reduced symptoms of colitis, as indicated by reduced disease activity index, and histopathology scores. Moreover, syringic acid administration enriched the abundance of Alistipes and norank_f__norank_o__Gastranaerophilales in mice, suggesting a restoration of impaired gut microbiota. Notably, we found that the effects of syringic acid were similar to those of fecal microbiota transplantation in dextran sulfate sodium-induced mice. Further analysis revealed that syringic acid inhibited the NLRP3-Cas-1-GSDMD-IL-1β inflammatory vesicle signaling pathway, leading to amelioration of colonic inflammation in a gut microbiota-dependent manner. Our findings demonstrate the potential of syringic acid as a preventive and therapeutic agent for inflammatory bowel disease.}, } @article {pmid37223860, year = {2023}, author = {Geng, Y and Shi, T and Wang, Y}, title = {Transmission of Hepatitis E Virus.}, journal = {Advances in experimental medicine and biology}, volume = {1417}, number = {}, pages = {73-92}, pmid = {37223860}, issn = {0065-2598}, abstract = {Transmission of hepatitis E virus (HEV) occurs predominantly by the fecal-oral route. Large epidemics of hepatitis E in the developing countries of Asia and Africa are waterborne and spread through contaminated drinking water. The reservoir of HEV in developed countries is believed to be in animals with zoonotic transmission to humans, possibly through direct contact or the consumption of undercooked contaminated meat. And HEV transmission through blood transfusion, organ transplantation, and vertical transmission has been reported.}, } @article {pmid37222345, year = {2023}, author = {Barbosa, EC and Bucar, EEC and Jubé, GR and Silveira, LB and Silva, NCD and Faria, PCC and Ramos, PLC and Moraes, VRY and Barros, JOB}, title = {Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {50}, number = {}, pages = {e20233490}, doi = {10.1590/0100-6991e-20233490-en}, pmid = {37222345}, issn = {1809-4546}, mesh = {Humans ; *Melanoma ; Fecal Microbiota Transplantation ; }, abstract = {INTRODUCTION: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota.

OBJECTIVE: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma.

METHODS: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic.

RESULTS: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response.

CONCLUSION: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.}, } @article {pmid37221272, year = {2023}, author = {Hsia, K and Zhao, N and Chung, M and Algarrahi, K and Kouhsari, LM and Fu, M and Chen, H and Singh, S and Michaud, DS and Jangi, S}, title = {Alterations in the Fungal Microbiome in Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izad082}, pmid = {37221272}, issn = {1536-4844}, support = {KL2TR002545/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis.

METHODS: We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n = 43), endohistologic activity (n = 41), and biologic exposure (n = 82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups.

RESULTS: We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P < 5 × 10-5) and increased Candida (log2 fold change = 2.56; adjusted P < .03). After adjusting for age, sex, and biologic exposure among patients with endoscopic activity, Saccharomyces (log2 fold change = 7.76; adjusted P < 1 × 10-15) and Candida (log2 fold change = 7.28; adjusted P< 1 × 10-8) remained enriched during endoscopic activity compared with quiescence.

CONCLUSIONS: Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.}, } @article {pmid37221233, year = {2023}, author = {Carvalho, T}, title = {First oral fecal microbiota transplant therapy approved.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41591-023-00046-2}, pmid = {37221233}, issn = {1546-170X}, } @article {pmid37220623, year = {2023}, author = {Benichou Haziot, C and Birak, KS}, title = {Therapeutic Potential of Microbiota Modulation in Alzheimer's Disease: A Review of Preclinical Studies.}, journal = {Journal of Alzheimer's disease reports}, volume = {7}, number = {1}, pages = {415-431}, pmid = {37220623}, issn = {2542-4823}, abstract = {Alzheimer's disease (AD) is the most common neurodegenerative disease, yet it currently lacks effective treatment due to its complex etiology. The pathological changes in AD have been linked to the neurotoxic immune responses following aggregation of Aβ and phosphorylated tau. The gut microbiota (GM) is increasingly studied for modulating neuroinflammation in neurodegenerative diseases and in vivo studies emerge for AD. This critical review selected 7 empirical preclinical studies from 2019 onwards assessing therapy approaches targeting GM modulating microglia neuroinflammation in AD mouse models. Results from probiotics, fecal microbiota transplantation, and drugs were compared and contrasted, including for cognition, neuroinflammation, and toxic aggregation of proteins. Studies consistently reported significant amelioration or prevention of cognitive deficits, decrease in microglial activation, and lower levels of pro-inflammatory cytokines, compared to AD mouse models. However, there were differences across papers for the brain regions affected, and changes in astrocytes were inconsistent. Aβ plaques deposition significantly decreased in all papers, apart from Byur dMar Nyer lNga Ril Bu (BdNlRB) treatment. Tau phosphorylation significantly declined in 5 studies. Effects in microbial diversity following treatment varied across studies. Findings are encouraging regarding the efficacy of study but information on the effect size is limited. Potentially, GM reverses GM derived abnormalities, decreasing neuroinflammation, which reduces AD toxic aggregations of proteins in the brain, resulting in cognitive improvements. Results support the hypothesis of AD being a multifactorial disease and the potential synergies through multi-target approaches. The use of AD mice models limits conclusions around effectiveness, as human translation is challenging.}, } @article {pmid37219936, year = {2023}, author = {Luo, Y and Tong, Y and Wu, L and Niu, H and Li, Y and Su, LC and Wu, Y and Bozec, A and Zaiss, MM and Qing, P and Zhao, H and Tan, C and Zhang, Q and Zhao, Y and Tang, H and Liu, Y}, title = {Alteration of gut microbiota in high-risk individuals for rheumatoid arthritis is associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.42616}, pmid = {37219936}, issn = {2326-5205}, abstract = {OBJECTIVE: We aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis.

DESIGN: Fecal samples were collected from 38 healthy individuals (HCs) and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA)-positivity (PreRA), 12 of 53 PreRA developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the HC and PreRA individuals or among PreRA subgroups were identified by 16S rRNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice received GM from the HC or PreRA groups were then evaluated for intestinal permeability, inflammatory cytokines and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from PreRA individuals on arthritis severity in mice.

RESULTS: Stool microbial diversity was lower in PreRA individuals than in HCs. The bacterial community structure and function significantly differed between HC and PreRA individuals. Although there were to some extent differences in the bacterial abundance among the PreRA subgroups, no robust functional differences were observed. The metabolites in the serum of the PreRA group were dramatically different from those in the HC group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the PreRA group increased intestinal permeability in FMT mice and ZO-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving PreRA feces compared to HC. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice.

CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to arthritis development.}, } @article {pmid37218816, year = {2023}, author = {Merrick, B and Sergaki, C and Edwards, L and Moyes, DL and Kertanegara, M and Prossomariti, D and Shawcross, DL and Goldenberg, SD}, title = {Modulation of the Gut Microbiota to Control Antimicrobial Resistance (AMR)-A Narrative Review with a Focus on Faecal Microbiota Transplantation (FMT).}, journal = {Infectious disease reports}, volume = {15}, number = {3}, pages = {238-254}, doi = {10.3390/idr15030025}, pmid = {37218816}, issn = {2036-7430}, abstract = {Antimicrobial resistance (AMR) is one of the greatest challenges facing humanity, causing a substantial burden to the global healthcare system. AMR in Gram-negative organisms is particularly concerning due to a dramatic rise in infections caused by extended-spectrum beta-lactamase and carbapenemase-producing Enterobacterales (ESBL and CPE). These pathogens have limited treatment options and are associated with poor clinical outcomes, including high mortality rates. The microbiota of the gastrointestinal tract acts as a major reservoir of antibiotic resistance genes (the resistome), and the environment facilitates intra and inter-species transfer of mobile genetic elements carrying these resistance genes. As colonisation often precedes infection, strategies to manipulate the resistome to limit endogenous infections with AMR organisms, as well as prevent transmission to others, is a worthwhile pursuit. This narrative review presents existing evidence on how manipulation of the gut microbiota can be exploited to therapeutically restore colonisation resistance using a number of methods, including diet, probiotics, bacteriophages and faecal microbiota transplantation (FMT).}, } @article {pmid37217962, year = {2023}, author = {Wang, C and Lin, Y and Chen, L and Chen, H}, title = {Gut microbiota mediated the effects of high relative humidity on lupus in female MRL/lpr mice.}, journal = {Advances in rheumatology (London, England)}, volume = {63}, number = {1}, pages = {24}, pmid = {37217962}, issn = {2523-3106}, abstract = {INTRODUCTION: The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored.

METHODS: The present study aimed to investigate the impact of high humidity (80 ± 5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50 ± 5%), allowing for an assessment of the effect of FMT on lupus.

RESULTS: The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice.

CONCLUSION: In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.}, } @article {pmid37217087, year = {2023}, author = {Fu, C and Ni, J and Huang, R and Gao, Y and Li, S and Li, Y and JinjinLi, and Zhong, K and Zhang, P}, title = {Sex different effect of antibiotic and probiotic treatment on intestinal microbiota composition in chemically induced liver injury rats.}, journal = {Genomics}, volume = {}, number = {}, pages = {110647}, doi = {10.1016/j.ygeno.2023.110647}, pmid = {37217087}, issn = {1089-8646}, abstract = {Differences in the gut microbiota and metabolic processes between males and females may explain differences in the risk of liver injury; however, the sex-specific effects of antibiotics and probiotics on these relationships are not clear. We evaluated differences in the gut microbiota and the risk of liver injury between male and female rats after the oral administration of antibiotics or probiotics followed by a period of diethylnitrosamine treatment to chemically induce liver injuryusing high-throughput sequencing of fecal microbiota combined with histological analyses of liver and colon tissues. Our results suggest that the ratio of gram-positive to gram-negative bacteria in kanamycin-treated rats was significantly higher than that of other groups, and this difference persisted for the duration of the experiment. Antibiotics significantly changed the composition of the gut microbiota of experimental rats. Clindamycin caused more diethylnitrosamine-induced damage to livers of male rats. Probiotics did not influencethe gut microbiota; however, they hadprotective effects against liver injury induced by diethylnitrosamine, especially in female rats. These results strengthen our understanding of sex differences in the indirect effects of antibiotics or probiotics on metabolism and liver injury in hosts via the gut microbiota.}, } @article {pmid37216289, year = {2023}, author = {Groenewegen, B and Terveer, EM and Joosse, A and Barnhoorn, MC and Zwittink, RD}, title = {Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {}, number = {}, pages = {}, doi = {10.1097/CJI.0000000000000474}, pmid = {37216289}, issn = {1537-4513}, abstract = {Immune checkpoint inhibitors (ICIs) have improved the prognosis in multiple cancer types. However, ICIs can induce immune-related adverse events such as immune-mediated enterocolitis (IMC). The gut microbiota may be implicated in IMC development. Therefore, we investigated fecal microbiota transplantation (FMT) as a treatment option for 2 patients with metastatic cancer suffering from refractory IMC. The patients were treated with, respectively, 1 and 3 FMTs after vancomycin pre-treatment. We monitored defecation frequency, fecal calprotectin, and microbiota composition. After FMT, both patients improved in defecation frequency, were discharged from the hospital, and received lower dosage of immunosuppressive therapy. Patient 1 developed an invasive pulmonary aspergillosis deemed to be related to prolonged steroid exposure. Patient 2 suffered from a Campylobacter jejuni infection after the first FMT and was treated with meropenem, resulting in a low-diversity microbiota profile and increased calprotectin levels and defecation frequency. After a second and third FMT, bacterial diversity increased and defecation frequency and calprotectin levels decreased. Pre-FMT, both patients showed low bacterial richness, but varying bacterial diversity. After FMT, diversity and richness were similar to healthy donor levels. In conclusion, FMT resulted in improvement of IMC symptoms and corresponding microbial changes in 2 cancer patients with refractory IMC. While more research is warranted, microbiome-modulation could be a promising new therapeutic option for IMC.}, } @article {pmid37216124, year = {2023}, author = {Markandey, M and Bajaj, A and Verma, M and Virmani, S and Singh, MK and Gaur, P and Das, P and Srikanth, CV and Makharia, G and Kedia, S and Ahuja, V}, title = {Fecal microbiota transplantation refurbishes the crypt-associated microbiota in ulcerative colitis.}, journal = {iScience}, volume = {26}, number = {5}, pages = {106738}, doi = {10.1016/j.isci.2023.106738}, pmid = {37216124}, issn = {2589-0042}, abstract = {A crypt autochthonous microbial population called crypt-associated microbiota (CAM) is localized intimately with gut regenerative and immune machinery. The present report utilizes laser capture microdissection coupled with 16S amplicon sequencing to characterize the CAM in patients with ulcerative colitis (UC) before and after fecal microbiota transplantation with anti-inflammatory diet (FMT-AID). Compositional differences in CAM and its interactions with mucosa-associated microbiota (MAM) were compared between the non-IBD controls and in patients with UC pre- and post-FMT (n = 26). Distinct from the MAM, CAM is dominated by aerobic members of Actinobacteria and Proteobacteria and exhibits resilience of diversity. CAM underwent UC-associated dysbiosis and demonstrated restoration post-FMT-AID. These FMT-restored CAM taxa correlated negatively with disease activity in patients with UC. The positive effects of FMT-AID extended further in refurbishing CAM-MAM interactions, which were obliterated in UC. These results encourage investigation into host-microbiome interactions established by CAM, to understand their role in disease pathophysiology.}, } @article {pmid37215136, year = {2023}, author = {Sun, Y and Wang, K and Zhao, W}, title = {Gut microbiota in perioperative neurocognitive disorders: current evidence and future directions.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1178691}, doi = {10.3389/fimmu.2023.1178691}, pmid = {37215136}, issn = {1664-3224}, abstract = {Perioperative neurocognitive disorders (PND) is a common surgical anesthesia complication characterized by impairment of memory, attention, language understanding and social ability, which can lead to a decline in the quality of life of patients, prolong the hospitalization period and increase the mortality rate. PND has a high incidence rate, which has a great impact on postoperative recovery and quality of life of patients, and has caused a heavy economic burden to society and families. In recent years, PND has become an important public health problem. The high risk population of PND is more prone to gut microbiota imbalance, and gut microbiota may also affect the inflammatory response of the central nervous system through the microbiota-gut-brain axis. Meanwhile, Neuroinflammation and immune activation are important mechanisms of PND. Regulating gut microbiota through probiotics or fecal bacteria transplantation can significantly reduce neuroinflammation, reduce the abnormal activation of immune system and prevent the occurrence of PND. This review summarizes the research progress of gut microbiota and PND, providing basis for the prevention and treatment of PND.}, } @article {pmid37214858, year = {2023}, author = {Bleich, RM and Li, C and Sun, S and Barlogio, CJ and Broberg, CA and Franks, AR and Bulik-Sullivan, E and Dogan, B and Simpson, KW and Carroll, IM and Fodor, AA and Arthur, JC}, title = {A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-2899665/v1}, pmid = {37214858}, abstract = {Background Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo . To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. Results Germ-free inflammation-susceptible interleukin-10-deficient (Il10 [-/-]) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10 [-/-] mice. These E. coli expand in Il10 [-/-] mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. Conclusions Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.}, } @article {pmid37214214, year = {2023}, author = {Yi, W and Huang, Q and Wang, Y and Shan, T}, title = {Lipo-nutritional quality of pork: The lipid composition, regulation, and molecular mechanisms of fatty acid deposition.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {13}, number = {}, pages = {373-385}, doi = {10.1016/j.aninu.2023.03.001}, pmid = {37214214}, issn = {2405-6383}, abstract = {Pork is one of the main meats consumed by people, and its nutritional value is closely related to human health. The lipid deposition and composition of pork not only affect the sensory quality but also determine the nutritional quality of pork. The lipids in pork include triglycerides (TAG) and a small amount of cholesterol and phospholipids. TAG are the main lipids in skeletal muscle fat, which is divided into intermuscular fat and intramuscular fat (IMF). In addition to TAG, IMF also contains phospholipids, which are important factors affecting pork flavour. There are three types of fatty acids in TAG: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). PUFA, such as n-3 PUFA, have a beneficial effect on health, including the regulation of whole-body energy metabolism and protection against cardiovascular diseases. Therefore, regulating lipid deposition, especially the fatty acid composition, in pork is important for improving the nutritional quality for human health. Notably, several strategies, such as breeding, environmental control, and the nutritional regulation of lipid composition and deposition in pork, have been studied. More recently, faecal transplantation, molecular design breeding and non-coding RNA have been studied and proven useful for regulating lipid deposition in pigs. In this review, we mainly summarized and discussed the research findings to date on the lipid composition and regulation mechanisms of fatty acid deposition and provide new insights into efficient means of improving the lipid composition and lipo-nutritional quality of pork.}, } @article {pmid37213506, year = {2023}, author = {Zhang, Y and Zhang, J and Wu, J and Zhu, Q and Chen, C and Li, Y}, title = {Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1124454}, pmid = {37213506}, issn = {1664-302X}, abstract = {INTRODUCTION: Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota.

METHODS: A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed.

RESULTS: After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of "affective disorder microbiota" from psychologically stressed mice increased stress sensitivity relative to FMT of "normal microbiota" from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites.

DISCUSSION: Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.}, } @article {pmid37213403, year = {2023}, author = {Lahtinen, P and Jalanka, J and Mattila, E and Tillonen, J and Bergman, P and Satokari, R and Arkkila, P}, title = {Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {29}, number = {17}, pages = {2666-2678}, pmid = {37213403}, issn = {2219-2840}, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce.

AIM: To investigate FMT for the maintenance of remission in UC patients.

METHODS: Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 μg/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient's quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo.

RESULTS: The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups.

CONCLUSION: There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.}, } @article {pmid37212669, year = {2023}, author = {Wu, Y and Dong, Z and Jiang, X and Qu, L and Zhou, W and Sun, X and Hou, J and Xu, H and Cheng, M}, title = {Gut Microbiota Taxon-Dependent Transformation of Microglial M1/M2 Phenotypes Underlying Mechanisms of Spatial Learning and Memory Impairment after Chronic Methamphetamine Exposure.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0030223}, doi = {10.1128/spectrum.00302-23}, pmid = {37212669}, issn = {2165-0497}, abstract = {Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75[NTR]-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that Clostridia, Bacteroides, Lactobacillus, and Muribaculaceae might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75[NTR]/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. IMPORTANCE Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.}, } @article {pmid37212529, year = {2023}, author = {Kvaerner, AS and Andersen, AR and Henriksen, HB and Knudsen, MD and Johansen, AMW and Hjartåker, A and Bøhn, SK and Paur, I and Wiedswang, G and Smeland, S and Rounge, TB and Blomhoff, R and Berstad, P}, title = {Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.}, journal = {Cancer medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/cam4.6119}, pmid = {37212529}, issn = {2045-7634}, abstract = {BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients.

METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions.

RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively.

CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.}, } @article {pmid37211643, year = {2023}, author = {Rodig, NM and Weatherly, M and Kaplan, AL and Ballal, SA and Elisofon, SA and Daly, KP and Kahn, SA}, title = {Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients.}, journal = {Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1097/TP.0000000000004656}, pmid = {37211643}, issn = {1534-6080}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking.

METHODS: We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT.

RESULTS: Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss.

CONCLUSIONS: In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.}, } @article {pmid37211239, year = {2023}, author = {Varesi, A and Campagnoli, LIM and Chirumbolo, S and Candiano, B and Carrara, A and Ricevuti, G and Esposito, C and Pascale, A}, title = {The Brain-Gut-Microbiota Interplay in Depression: a key to design innovative therapeutic approaches.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106799}, doi = {10.1016/j.phrs.2023.106799}, pmid = {37211239}, issn = {1096-1186}, abstract = {Depression is the most prevalent mental disorder in the world associated with huge socio-economic consequences. While depressive-related symptoms are well known, the molecular mechanisms underlying disease pathophysiology and progression remain largely unknown. The gut microbiota (GM) is emerging as a key regulator of the central nervous system homeostasis by exerting fundamental immune and metabolic functions. In turn, the brain influences the intestinal microbial composition through neuroendocrine signals, within the so-called gut microbiota-brain axis. The balance of this bidirectional crosstalk is important to ensure neurogenesis, preserve the integrity of the blood-brain barrier and avoid neuroinflammation. Conversely, dysbiosis and gut permeability negatively affect brain development, behavior, and cognition. Furthermore, although not fully defined yet, changes in the GM composition in depressed patients are reported to influence the pharmacokinetics of common antidepressants by affecting their absorption, metabolism, and activity. Similarly, neuropsychiatric drugs may shape in turn the GM with an impact on the efficacy and toxicity of the pharmacological intervention itself. Consequently, strategies aimed at re-establishing the correct homeostatic gut balance (i.e., prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions) represent an innovative approach to improve the pharmacotherapy of depression. Among these, probiotics and the Mediterranean diet, alone or in combination with the standard of care, hold promise for clinical application. Therefore, the disclosure of the intricate network between GM and depression will give precious insights for innovative diagnostic and therapeutic approaches towards depression, with profound implications for drug development and clinical practice.}, } @article {pmid37211107, year = {2023}, author = {Hong, T and Zou, J and He, Y and Zhang, H and Liu, H and Mai, H and Yang, J and Cao, Z and Chen, X and Yao, J and Feng, D}, title = {Bisphenol A induced hepatic steatosis by disturbing bile acid metabolism and FXR/TGR5 signaling pathways via remodeling the gut microbiota in CD-1 mice.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {164307}, doi = {10.1016/j.scitotenv.2023.164307}, pmid = {37211107}, issn = {1879-1026}, abstract = {Dysregulation of gut microbiota-mediated bile acid (BA) metabolism plays an important role in the pathogenesis of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our previous studies found that bisphenol A (BPA) exposure induced hepatic steatosis and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alterations were involved in BPA-induced hepatic steatosis remains unclear. Therefore, we explored the gut microbiota-related metabolic mechanisms of hepatic steatosis induced by BPA. Male CD-1 mice were exposed to low-dose BPA (50 μg/kg/day) for 6 months. Fecal microbiota transplantation (FMT) and broad-spectrum antibiotic cocktail (ABX) treatment were further adopted to test the role of gut microbiota in the adverse effects of BPA. We found that BPA induced hepatic steatosis in mice. Additionally, 16S rRNA gene sequencing showed that BPA reduced the relative abundance of Bacteroides, Parabacteroides and Akkermansia, which are associated with BA metabolism. Metabolomic analyses demonstrated that BPA significantly altered the ratio of conjugated to unconjugated BAs and increased the total level of taurine-α/β-muricholic acid while decreasing the level of chenodeoxycholic acid, thus inhibiting the activation of special receptors, including farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), in the ileum and liver. The inhibition of FXR reduced short heterodimer partner and subsequently induced cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, which is related to hepatic BA synthesis and lipogenesis, eventually leading to liver cholestasis and steatosis. Furthermore, we found that mice that received FMT from BPA-exposed mice developed hepatic steatosis, and the influences of BPA on hepatic steatosis and FXR/TGR5 signaling could be eliminated by ABX treatment, confirming the role of gut microbiota in BPA effects. Collectively, our study illustrates that suppressed microbiota-BA-FXR/TGR signaling pathways may be a potential mechanism for hepatic steatosis induced by BPA, providing a new target for the prevention of BPA-induced NAFLD.}, } @article {pmid37210914, year = {2023}, author = {Chen, Y and Shu, A and Jiang, M and Jiang, J and Du, Q and Chen, T and Shaw, C and Chai, W and Chao, T and Li, X and Wu, Q and Gao, C}, title = {Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110339}, doi = {10.1016/j.intimp.2023.110339}, pmid = {37210914}, issn = {1878-1705}, abstract = {With the rising incidence of diabetes and its onset at a younger age, the impact on the male reproductive system has gradually gained attention. Exenatide is a glucagon-like peptide-1 receptor agonist effective in the treatment of diabetes. However, its role in diabetes-induced reproductive complications has rarely been reported. The study aimed to investigate the mechanism by which exenatide improved diabetic hypogonadism by regulating gut microbiota (GM) mediated inflammation. C57BL/6J mice were equally divided into normal control (NC), diabetic model control (DM) and exenatide-treated (Exe) groups. Testicular, pancreatic, colonic, and fecal samples were collected to assess microbiota, morphologic damage, and inflammation. Exenatide significantly reduced the fasting blood glucose (FBG) level in diabetic mice, increased the testosterone level, ameliorated the pathological morphological damage of islet, colon, and testes, and reduced the expression of pro-inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in colon and testis. Furthermore, exenatide significantly reduced the abundance of some pathogenic bacteria, such as Streptococcaceae and Erysipelotrichaceae, and increased that of beneficial bacteria Akkermansia. Probiotics, such as Lactobacillus were negatively correlated with TNF-α, nuclear factor-kappa-B (NF-κB), IL-6, and FBG. Conditional pathogenic bacteria such as Escherichia/Shigella Streptococcus were positively correlated with TNF-α, NF-κB, IL-6, and FBG. The fecal bacteria transplantation experiment revealed that the abundance of pathogenic bacteria, Peptostreptococcaceae, significantly decreased from Exe group mice to pseudo-sterile diabetic mice, and the pathological damage to testes was also alleviated. These data suggested the protective effects of exenatide on male reproductive damage induced by diabetes by regulating GM.}, } @article {pmid37208728, year = {2023}, author = {Yu, J and Meng, J and Qin, Z and Yu, Y and Liang, Y and Wang, Y and Min, D}, title = {Dysbiosis of gut microbiota inhibits NMNAT2 to promote neurobehavioral deficits and oxidative stress response in the 6-OHDA-lesioned rat model of Parkinson's disease.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {117}, pmid = {37208728}, issn = {1742-2094}, abstract = {BACKGROUND: New data are accumulating on gut microbial dysbiosis in Parkinson's disease (PD), while the specific mechanism remains uncharacterized. This study aims to investigate the potential role and pathophysiological mechanism of dysbiosis of gut microbiota in 6-hydroxydopamine (6-OHDA)-induced PD rat models.

METHODS: The shotgun metagenome sequencing data of fecal samples from PD patients and healthy individuals were obtained from the Sequence Read Archive (SRA) database. The diversity, abundance, and functional composition of gut microbiota were further analyzed in these data. After the exploration of the functional pathway-related genes, KEGG and GEO databases were used to obtain PD-related microarray datasets for differential expression analysis. Finally, in vivo experiments were performed to confirm the roles of fecal microbiota transplantation (FMT) and upregulated NMNAT2 in neurobehavioral symptoms and oxidative stress response in 6-OHDA-lesioned rats.

RESULTS: Significant differences were found in the diversity, abundance, and functional composition of gut microbiota between PD patients and healthy individuals. Dysbiosis of gut microbiota could regulate NAD[+] anabolic pathway to affect the occurrence and development of PD. As a NAD[+] anabolic pathway-related gene, NMNAT2 was poorly expressed in the brain tissues of PD patients. More importantly, FMT or overexpression of NMNAT2 alleviated neurobehavioral deficits and reduced oxidative stress in 6-OHDA-lesioned rats.

CONCLUSIONS: Taken together, we demonstrated that dysbiosis of gut microbiota suppressed NMNAT2 expression, thus exacerbating neurobehavioral deficits and oxidative stress response in 6-OHDA-lesioned rats, which could be rescued by FMT or NMNAT2 restoration.}, } @article {pmid37208544, year = {2023}, author = {Lange, O and Proczko-Stepaniak, M and Mika, A}, title = {Short-Chain Fatty Acids-A Product of the Microbiome and Its Participation in Two-Way Communication on the Microbiome-Host Mammal Line.}, journal = {Current obesity reports}, volume = {}, number = {}, pages = {}, pmid = {37208544}, issn = {2162-4968}, abstract = {PURPOSE OF REVIEW: The review aims to describe short-chain fatty acids (SCFAs) as metabolites of bacteria, their complex influence on whole-body metabolism, and alterations in the SCFA profile in obesity and after bariatric surgery (BS).

RECENT FINDINGS: The fecal profile of SCFAs in obese patients differs from that of lean patients, as well as their gut microbiota composition. In obese patients, a lower diversity of bacteria is observed, as well as higher concentrations of SCFAs in stool samples. Obesity is now considered a global epidemic and bariatric surgery (BS) is an effective treatment for severe obesity. BS affects the structure and functioning of the digestive system, and also alters gut microbiota and the concentration of fecal SCFAs. Generally, after BS, SCFA levels are lower but levels of branched short-chain fatty acids (BSCFAs) are elevated, the effect of which is not fully understood. Moreover, changes in the profile of circulating SCFAs are little known and this is an area for further research. Obesity seems to be inherently associated with changes in the SCFA profile. It is necessary to better understand the impact of BS on microbiota and the metabolome in both feces and blood as only a small percentage of SCFAs are excreted. Further research may allow the development of a personalized therapeutic approach to the BS patient in terms of diet and prebiotic intervention.}, } @article {pmid37207204, year = {2023}, author = {Hamada, K and Isobe, J and Hattori, K and Hosonuma, M and Baba, Y and Murayama, M and Narikawa, Y and Toyoda, H and Funayama, E and Tajima, K and Shida, M and Hirasawa, Y and Tsurui, T and Ariizumi, H and Ishiguro, T and Suzuki, R and Ohkuma, R and Kubota, Y and Sambe, T and Tsuji, M and Wada, S and Kiuchi, Y and Kobayashi, S and Kuramasu, A and Horiike, A and Kim, YG and Tsunoda, T and Yoshimura, K}, title = {Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1164724}, pmid = {37207204}, issn = {1664-3224}, abstract = {INTRODUCTION: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown.

METHODS: We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).

RESULTS: The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.

DISCUSSION: Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.}, } @article {pmid37205307, year = {2023}, author = {Kouidhi, S and Zidi, O and Belkhiria, Z and Rais, H and Ayadi, A and Ben Ayed, F and Mosbah, A and Cherif, A and El Gaaied, ABA}, title = {Gut microbiota, an emergent target to shape the efficiency of cancer therapy.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {4}, number = {2}, pages = {240-265}, pmid = {37205307}, issn = {2692-3114}, abstract = {It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota's role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance.}, } @article {pmid37205106, year = {2023}, author = {Wang, M and Zhang, Y and Li, C and Chang, W and Zhang, L}, title = {The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1180336}, doi = {10.3389/fimmu.2023.1180336}, pmid = {37205106}, issn = {1664-3224}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.}, } @article {pmid37204063, year = {2023}, author = {Zhao, X and Zhang, T and Zheng, Y and Zhao, Z and Ding, W and Zhang, Z and Zhang, Z and Wang, R and Jiao, M and Liu, L and Yu, S and Wang, X and Huang, R and Wu, Q}, title = {Gut Microbiota from Short-Chain Chlorinated Paraffin-Exposed Mice Promotes Astrocyte Activation by Disrupting the Intestinal Tight Junction via Zonulin Upregulation.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c01058}, pmid = {37204063}, issn = {1520-5118}, abstract = {Short-chain chlorinated paraffins (SCCPs) are novel toxicants in food and are reported to possess neurotoxicity. Here, we investigated the mechanism of SCCP-induced astrocyte activation and neuroinflammation. SCCP gavage induced astrocyte activation and neuronal cell death with the changes of gut microbiome and metabolites. Antibiotic cocktail administration to deplete the gut microbiome ameliorated the astrocyte activation and inflammation induced by SCCPs. In fecal microbiota transplantation (FMT) assays, mice that received transplanted gut microbiome from SCCP-treated mice showed increased astrocyte activation and elevated inflammatory response. In addition, SCCP exposure promotes zonulin expression and tight junction injury, and antibiotic cocktail administration inhibited that in the intestinal tract. Increased zonulin and tight junction injury were also observed in SCCPs_FMT mice. The zonulin inhibition protected the tight junction in the intestinal tract from SCCP exposure and suppressed astrocyte activation. In summary, this study proposes a novel possibility for SCCP-induced astrocyte activation and neurotoxicity by the gut microbiome-mediated zonulin expression and tight junction.}, } @article {pmid37203380, year = {2023}, author = {Zhou, W and Liu, P and Xu, W and Ran, L and Yan, Y and Lu, L and Zeng, X and Cao, Y and Mi, J}, title = {A purified fraction of polysaccharides from the fruits of Lycium barbarum L. improves glucose homeostasis and intestinal barrier function in high-fat diet-fed mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo00262d}, pmid = {37203380}, issn = {2042-650X}, abstract = {High-fat diet (HFD) consumption can induce intestinal barrier dysfunction and disrupt glucose metabolism. Our previous studies have demonstrated that polysaccharides obtained from the fruits of Lycium barbarum L. (LBPs) could suppress acute experimental diabetes as well as colitis in mice. In the present study, the modulating effects of a purified fraction of LBPs, named LBPs-4, on glucose homeostasis and intestinal barrier function in mice fed with a HFD were investigated. Our results indicated that the oral administration of LBP-4 (200 mg per kg per day) improved hyperglycemia, glucose intolerance, insulin resistance and islet β-cell hyperplasia in HFD-fed mice. Moreover, LBPs-4 intervention enhanced the intestinal barrier integrity by increasing the expression levels of zonula occludens 1 and claudin-1 and the number of goblet cells in the colon. LBPs-4 also modulated the composition of gut microbiota by increasing the relative abundances of butyrate producer Allobaculum and acetate producer Romboutsia. The results of fecal transplantation experiments, transferring of microbiota from LBPs-4-fed donor mice to HFD-fed recipient mice, validated the cause-effect relationship between LBPs-4-evoked changes in the gut microbiota and improvement of glucose homeostasis and intestinal barrier function. Collectively, these findings suggested that LBPs-4 might be developed as promising prebiotics to improve glucose metabolism and gut health.}, } @article {pmid37202543, year = {2023}, author = {Zeng, N and Wu, F and Lu, J and Li, X and Lin, S and Zhou, L and Wang, Z and Wu, G and Huang, Q and Zheng, D and Gao, J and Wu, S and Chen, X and Chen, M and Meng, F and Shang, H and He, Y and Chen, P and Wei, H and Li, Z and Zhou, H}, title = {High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {37202543}, issn = {1869-1889}, abstract = {Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet (HFD)-associated metabolic disorders. However, the underlying mechanism remains elusive. In the present study, by comparing HFD- and normal diet (ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier. Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions, as confirmed by the increased reactive oxygen species (ROS) levels in fecal microbiota incubation in vitro and in the lumen, which were detected using in vivo fluorescence imaging. This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation (FMT) into germ-free (GF) mice, downregulating the gut barrier tight junctions. Similarly, mono-colonizing GF mice with an Enterococcus strain excelled in ROS production, damaged the gut barrier, induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells, and exacerbated fatty liver, compared with other low-ROS-producing Enterococcus strains. Oral administration of recombinant high-stability-superoxide dismutase (SOD) significantly reduced intestinal ROS, protected the gut barrier, and improved fatty liver against the HFD. In conclusion, our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.}, } @article {pmid37201335, year = {2023}, author = {Laragione, T and Harris, C and Azizgolshani, N and Beeton, C and Bongers, G and Gulko, PS}, title = {Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome.}, journal = {EBioMedicine}, volume = {92}, number = {}, pages = {104603}, doi = {10.1016/j.ebiom.2023.104603}, pmid = {37201335}, issn = {2352-3964}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored.

METHODS: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT).

FINDINGS: The high Mg diet group was significantly protected with reduced arthritis severity and joint damage, and reduced expression of IL-1β, IL-6, and TNFα. The high Mg group also had increased numbers of Foxp3+ Treg cells and IL-10-producing T cells. The high Mg protective effect disappeared in IL-10 knockout mice. FMT from the high Mg diet mice recreated the phenotypes seen in the diet-treated mice, with reduced arthritis severity, increased Foxp3+ Treg, and increased IL-10-producing T cells. Intestinal microbiome analyses using 16S rDNA sequencing revealed diet-specific changes, including reduced levels of RA-associated Prevotella in the high Mg group, while increasing levels of Bacteroides and other bacteria associated with increased production of short-chain fatty acids. Metagenomic analyses implicated additional pathways including L-tryptophan biosynthesis and arginine deiminase.

INTERPRETATION: We describe a new role for Mg in suppressing arthritis, in expanding Foxp3+ T reg cells and in the production of IL-10, and show that these effects are mediated by the intestinal microbiome. Our discoveries suggest a novel strategy for modifying the intestinal microbiome to treat RA and other autoimmune and inflammatory diseases.

FUNDING: None.}, } @article {pmid37200942, year = {2023}, author = {Jiang, Z and Wang, X and Zhang, H and Yin, J and Zhao, P and Yin, Q and Wang, Z}, title = {Ketogenic diet protects MPTP-induced mouse model of Parkinson's disease via altering gut microbiota and metabolites.}, journal = {MedComm}, volume = {4}, number = {3}, pages = {e268}, pmid = {37200942}, issn = {2688-2663}, abstract = {The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.}, } @article {pmid37200041, year = {2023}, author = {Zhang, B and Li, J and Fu, J and Shao, L and Yang, L and Shi, J}, title = {Interaction between mucus layer and gut microbiota in NAFLD: Soil and seeds.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {37200041}, issn = {2542-5641}, abstract = {The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.}, } @article {pmid37199714, year = {2023}, author = {Bai, Y and Meng, Q and Wang, C and Ma, K and Li, J and Li, J and Shan, A}, title = {Gut Microbiota Mediates Lactobacillus rhamnosus GG Alleviation of Deoxynivalenol-Induced Anorexia.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c08076}, pmid = {37199714}, issn = {1520-5118}, abstract = {Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; Lactobacillus rhamnosus GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of Lactobacillus and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.}, } @article {pmid37199635, year = {2023}, author = {Tao, Z and Chen, Y and He, F and Tang, J and Zhan, L and Hu, H and Ding, Z and Ruan, S and Chen, Y and Chen, B and Wang, Y and Guo, X and Xie, L and Zhong, M and Huang, Q}, title = {Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0007623}, doi = {10.1128/spectrum.00076-23}, pmid = {37199635}, issn = {2165-0497}, abstract = {Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases.}, } @article {pmid37199590, year = {2023}, author = {Xie, Z and Zhang, M and Luo, Y and Jin, D and Guo, X and Yang, W and Zheng, J and Zhang, H and Zhang, L and Deng, C and Zheng, W and Tan, EK and Jin, K and Zhu, S and Wang, Q}, title = {Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2023.0309}, pmid = {37199590}, issn = {2152-5250}, abstract = {Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.}, } @article {pmid37198039, year = {2023}, author = {Emile, SH and Garoufalia, Z and Aeschbacher, P and Horesh, N and Gefen, R and Wexner, SD}, title = {Endorectal advancement flap compared to ligation of inter-sphincteric fistula tract in the treatment of complex anal fistulas: A meta-analysis of randomized clinical trials.}, journal = {Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.surg.2023.04.004}, pmid = {37198039}, issn = {1532-7361}, abstract = {BACKGROUND: Rectal advancement flap and ligation of intersphincteric fistula tract are common procedures for treating complex anal fistula. The present meta-analysis aimed to compare the surgical outcomes of advancement flap and ligation of intersphincteric fistula tract.

METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of randomized clinical trials comparing the ligation of intersphincteric fistula tract and advancement flap was conducted. PubMed, Scopus, and Web of Science were searched through January 2023. The risk of bias was assessed using the Risk of Bias 2 tool and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. The primary outcomes were healing and recurrence of anal fistulas, and secondary outcomes were operative time, complications, fecal incontinence, and early pain.

RESULTS: Three randomized clinical trials (193 patients, 74.6% male) were included. The median follow-up was 19.2 months. Two trials had a low risk of bias, and 1 had some risk of bias. The odds of healing (odds ratio: 1.363, 95% confidence interval: 0.373-4.972, P = .639), recurrence (odds ratio: 0.525, 95% confidence interval: 0.263-1.047, P = .067), and complications (odds ratio: 0.356, 95% confidence interval: 0.085-1.487, P = .157) were similar between the 2 procedures. Ligation of intersphincteric fistula tract was associated with a significantly shorter operation time (weighted mean difference: -4.876, 95% confidence interval: -7.988 to -1.764, P = .002) and less postoperative pain (weighted mean difference: -1.030, 95% confidence interval: -1.418 to -0.641, 0.198, P < .001, I[2] = 3.85%) than advancement flap. Ligation of intersphincteric fistula tract was associated with marginally lower odds of fecal incontinence than advancement flap (odds ratio: 0.27, 95% confidence interval: 0.069-1.06, P = .06).

CONCLUSION: Ligation of intersphincteric fistula tract and advancement flap had similar odds of healing, recurrence, and complications. The odds of fecal incontinence and extent of pain after ligation of intersphincteric fistula tract were lower than after advancement flap.}, } @article {pmid37197060, year = {2023}, author = {Yang, W and Xia, Z and Zhu, Y and Tang, H and Xu, H and Hu, X and Lin, C and Jiang, T and He, P and Shen, J}, title = {Comprehensive Study of Untargeted Metabolomics and 16S rRNA Reveals the Mechanism of Fecal Microbiota Transplantation in Improving a Mouse Model of T2D.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {16}, number = {}, pages = {1367-1381}, pmid = {37197060}, issn = {1178-7007}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a new therapy targeting gastrointestinal microbiota for the treatment of a growing number of diseases in recent years. Previous studies have suggested that FMT may be a potential therapy for type 2 diabetes (T2D), but the underlying mechanism remains unclear. Therefore, in the present study, we aimed to investigate the role of FMT in T2D and its underlying mechanisms.

METHODS: To induce T2D, mice were fed a high-fat diet and injected with low-dose streptozotocin (STZ) for four weeks. The mice were then randomly divided into four groups: control group (n = 7), T2D group (n = 7), metformin (MET)-treated group (n = 7), and FMT group (n = 7). The MET group was orally administered 0.2 g/kg MET, the FMT group was orally administered 0.3 mL of bacterial solution, and the other two groups were orally administered the same volume of saline for four weeks. Serum and fecal samples were collected for non-targeted metabolomics, biochemical indicators, and 16S rRNA sequencing, respectively.

RESULTS: Our results demonstrated that FMT had a curative effect on T2D by ameliorating hyperlipidemia and hyperglycemia. Using 16S rRNA sequencing and serum untargeted metabolomic analysis, we found that FMT could restore the disorders of gastrointestinal microbiota in T2D mice. Moreover, corticosterone, progesterone, L-urobilin, and other molecules were identified as biomarkers after FMT treatment. Our bioinformatics analysis suggested that steroid hormone biosynthesis, arginine, proline metabolism, and unsaturated fatty acid biosynthesis could be potential regulatory mechanisms of FMT.

CONCLUSION: In summary, our study provides comprehensive evidence for the role of FMT in the treatment of T2D. FMT has the potential to become a promising strategy for the treatment of metabolic disorders, T2D, and diabetes-related complications.}, } @article {pmid37196685, year = {2023}, author = {Fang, C and Zuo, K and Liu, Z and Liu, Y and Liu, L and Wang, Y and Yin, X and Li, J and Liu, X and Chen, M and Yang, X}, title = {Disordered gut microbiota promotes atrial fibrillation by aggravated conduction disturbance and unbalanced Linoleic acid/SIRT1 signaling.}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {115599}, doi = {10.1016/j.bcp.2023.115599}, pmid = {37196685}, issn = {1873-2968}, abstract = {Emerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.}, } @article {pmid37196633, year = {2023}, author = {Yadav, J and Liang, T and Qin, T and Nathan, N and Schwenger, KJP and Pickel, L and Xie, L and Lei, H and Winer, DA and Maughan, H and Robertson, SJ and Woo, M and Lou, W and Banks, K and Jackson, T and Okrainec, A and Hota, SS and Poutanen, SM and Sung, HK and Allard, JP and Philpott, DJ and Gaisano, HY}, title = {Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure.}, journal = {Cell reports. Medicine}, volume = {4}, number = {5}, pages = {101051}, doi = {10.1016/j.xcrm.2023.101051}, pmid = {37196633}, issn = {2666-3791}, abstract = {Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.}, } @article {pmid37196556, year = {2023}, author = {Liu, H and Kang, X and Ren, P and Kuang, X and Yang, X and Yang, H and Shen, X and Yan, H and Kang, Y and Zhang, F and Wang, X and Guo, L and Fan, W}, title = {Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110252}, doi = {10.1016/j.intimp.2023.110252}, pmid = {37196556}, issn = {1878-1705}, abstract = {Alcoholic liver disease (ALD) is a globally prevalent liver-related disorder characterized by severe oxidative stress and inflammatory liver damage, for which no effective treatment is currently available. Hydrogen gas (H2) has been demonstrated to be an efficient antioxidant in various diseases in animals as well as humans. However, the protective effects of H2 on ALD and its underlying mechanisms remain to be elucidated. The present study demonstrated that H2 inhalation ameliorated liver injury, and attenuated liver oxidative stress, inflammation, and steatosis in an ALD mouse model. Moreover, H2 inhalation improved gut microbiota, including increasing the abundance of Lachnospiraceae and Clostridia, and decreasing the abundance of Prevotellaceae and Muribaculaceae, and also improved intestinal barrier integrity. Mechanistically, H2 inhalation blocked activation of the LPS/TLR4/NF-κB pathway in liver. Notably, it was further demonstrated that the reshaped gut microbiota may accelerate alcohol metabolism, regulate lipid homeostasis and maintain immune balance by bacterial functional potential prediction (PICRUSt). Fecal microbiota transplantation from mice that had undergone H2 inhalation significantly alleviated acute alcoholic liver injury. In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context.}, } @article {pmid37193034, year = {2023}, author = {Huang, X and Zhang, Y and Huang, J and Gao, W and Yongfang, X and Zeng, C and Gao, C}, title = {The effect of FMT and vitamin C on immunity-related genes in antibiotic-induced dysbiosis in mice.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15356}, pmid = {37193034}, issn = {2167-8359}, abstract = {Antibiotics are double-edged swords. Although antibiotics are used to inhibit pathogenic bacteria, they also run the risk of destroying some of the healthy bacteria in our bodies. We examined the effect of penicillin on the organism through a microarray dataset, after which 12 genes related to immuno-inflammatory pathways were selected by reading the literature and validated using neomycin and ampicillin. The expression of genes was measured using qRT-PCR. Several genes were significantly overexpressed in antibiotic-treated mice, including CD74 and SAA2 in intestinal tissues that remained extremely expressed after natural recovery. Moreover, transplantation of fecal microbiota from healthy mice to antibiotic-treated mice was made, where GZMB, CD3G, H2-AA, PSMB9, CD74, and SAA1 were greatly expressed; however, SAA2 was downregulated and normal expression was restored, and in liver tissue, SAA1, SAA2, SAA3 were extremely expressed. After the addition of vitamin C, which has positive effects in several aspects, to the fecal microbiota transplantation, in the intestinal tissues, the genes that were highly expressed after the fecal microbiota transplantation effectively reduced their expression, and the unaffected genes remained normally expressed, but the CD74 gene remained highly expressed. In liver tissues, normally expressed genes were not affected, but the expression of SAA1 was reduced and the expression of SAA3 was increased. In other words, fecal microbiota transplantation did not necessarily bring about a positive effect of gene expression restoration, but the addition of vitamin C effectively reduced the effects of fecal microbiota transplantation and regulated the balance of the immune system.}, } @article {pmid37192676, year = {2023}, author = {Meng, Y and Sun, J and Zhang, G}, title = {Fecal microbiota transplantation holds the secret to youth.}, journal = {Mechanisms of ageing and development}, volume = {}, number = {}, pages = {111823}, doi = {10.1016/j.mad.2023.111823}, pmid = {37192676}, issn = {1872-6216}, abstract = {Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.}, } @article {pmid37192552, year = {2023}, author = {Liu, J and Cai, J and Fan, P and Dong, X and Zhang, N and Tai, J and Cao, Y}, title = {Salidroside protects mice from high-fat diet-induced obesity by modulating the gut microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110278}, doi = {10.1016/j.intimp.2023.110278}, pmid = {37192552}, issn = {1878-1705}, abstract = {Obesity is a systemic disease with multisystem inflammation associated with gut dysbiosis. Salidroside (SAL) which is a major glycoside extracted from Rhodiola rosea L. has a wide range of pharmacological effects, but the role of gut microbiota in the protective effects of SAL on obesity has not been studied. Herein, we aim to explore whether SAL could ameliorate high-fat diet (HFD)-induced obesity in mice by modulating microbiota. Results showed that oral treatment with SAL alleviated HFD-induced obesity in mice as evidenced by body weight and fat weight. SAL supplementation effectively attenuated fat accumulation, lipid synthesis genes expression, liver inflammation, and metabolic endotoxemia. In addition, SAL treatment alleviated intestinal damage and increased the expression of mucin protein (Mucin-2) and tight junction (TJ) proteins (Occludin and Zonula Occludens-1). 16S rRNA sequencing analysis revealed that the gut microbiota of obese mice was also partly improved by SAL via restoring the microbial community structure and diversity. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with fecal transplantation (FM) from the HFD-treated mice, FM from the SAL-treated mice significantly mitigate the symptoms of obese mice, including decreasing body weight, fat accumulation, and attenuating pathological damage in the gut. Thus, SAL could be a remarkable candidate to prevent obesity.}, } @article {pmid37191418, year = {2023}, author = {Zou, B and Li, J and Ma, RX and Cheng, XY and Ma, RY and Zhou, TY and Wu, ZQ and Yao, Y and Li, J}, title = {Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review.}, journal = {Aging and disease}, volume = {14}, number = {3}, pages = {964-1678}, doi = {10.14336/AD.2022.1127}, pmid = {37191418}, issn = {2152-5250}, abstract = {Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.}, } @article {pmid37191003, year = {2023}, author = {Jiang, H and Ye, Y and Wang, M and Sun, X and Sun, T and Chen, Y and Li, P and Zhang, M and Wang, T}, title = {The progress on the relationship between gut microbiota and immune checkpoint blockade in tumors.}, journal = {Biotechnology & genetic engineering reviews}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/02648725.2023.2212526}, pmid = {37191003}, issn = {2046-5556}, abstract = {Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.}, } @article {pmid37189804, year = {2023}, author = {Tews, HC and Elger, T and Grewal, T and Weidlich, S and Vitali, F and Buechler, C}, title = {Fecal and Urinary Adipokines as Disease Biomarkers.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, doi = {10.3390/biomedicines11041186}, pmid = {37189804}, issn = {2227-9059}, abstract = {The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.}, } @article {pmid37189634, year = {2023}, author = {Boicean, A and Birlutiu, V and Ichim, C and Anderco, P and Birsan, S}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, doi = {10.3390/biomedicines11041016}, pmid = {37189634}, issn = {2227-9059}, abstract = {Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn's disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host's immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.}, } @article {pmid37187187, year = {2023}, author = {Stallmach, A and von Müller, L and Storr, M and Link, A and Konturek, PC and Solbach, PC and Weiss, KH and Wahler, S and Vehreschild, MJGT}, title = {[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2075-2725}, pmid = {37187187}, issn = {1439-7803}, abstract = {INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far.

MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation.

RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%.

DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.}, } @article {pmid37185024, year = {2023}, author = {Lukáčová, I and Ambro, Ľ and Dubayová, K and Mareková, M}, title = {The gut microbiota, its relationship to the immune system, and possibilities of its modulation.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {72}, number = {1}, pages = {40-53}, pmid = {37185024}, issn = {1210-7913}, abstract = {Research of the gut microbiota allows a better understanding of its composition and function and reveals the links between changes in the composition of bacteria and various intestinal but also systemic diseases. The gut microbiota performs several of important functions in the host body and influences many physiological processes. Gut bacteria synthesize many compounds needed for the proper function of the body (e.g., vitamins, short-chain fatty acids, and amino acids). They help maintain the integrity of the intestinal barrier and protect against pathogens. The gut microbiota plays a crucial role in the development and function of the immune system. Significant changes in the composition of the intestinal microbiota led to a dysbiotic state and the loss of its beneficial functions for humans. The review article summarizes the basic knowledge about the composition and function of the bacterial gut microbiota in healthy people, its role in the development of the immune system, and the mechanisms involved in maintaining homeostasis. It also presents current knowledge about the possibility of targeted modulation of the bacterial gut microbiota and faecal transplantation.}, } @article {pmid37180433, year = {2023}, author = {Fan, H and Liu, X and Ren, Z and Fei, X and Luo, J and Yang, X and Xue, Y and Zhang, F and Liang, B}, title = {Gut microbiota and cardiac arrhythmia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1147687}, pmid = {37180433}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Arrhythmias, Cardiac ; *Probiotics/therapeutic use ; Prebiotics ; Inflammation/metabolism ; Dysbiosis ; }, abstract = {One of the most prevalent cardiac diseases is cardiac arrhythmia, however the underlying causes are not entirely understood. There is a lot of proof that gut microbiota (GM) and its metabolites have a significant impact on cardiovascular health. In recent decades, intricate impacts of GM on cardiac arrythmia have been identified as prospective approaches for its prevention, development, treatment, and prognosis. In this review, we discuss about how GM and its metabolites might impact cardiac arrhythmia through a variety of mechanisms. We proposed to explore the relationship between the metabolites produced by GM dysbiosis including short-chain fatty acids(SCFA), Indoxyl sulfate(IS), trimethylamine N-oxide(TMAO), lipopolysaccharides(LPS), phenylacetylglutamine(PAGln), bile acids(BA), and the currently recognized mechanisms of cardiac arrhythmias including structural remodeling, electrophysiological remodeling, abnormal nervous system regulation and other disease associated with cardiac arrythmia, detailing the processes involving immune regulation, inflammation, and different types of programmed cell death etc., which presents a key aspect of the microbial-host cross-talk. In addition, how GM and its metabolites differ and change in atrial arrhythmias and ventricular arrhythmias populations compared with healthy people are also summarized. Then we introduced potential therapeutic strategies including probiotics and prebiotics, fecal microbiota transplantation (FMT) and immunomodulator etc. In conclusion, the GM has a significant impact on cardiac arrhythmia through a variety of mechanisms, offering a wide range of possible treatment options. The discovery of therapeutic interventions that reduce the risk of cardiac arrhythmia by altering GM and metabolites is a real challenge that lies ahead.}, } @article {pmid37179170, year = {2023}, author = {Xin, Y and Huang, C and Zheng, M and Zhou, W and Zhang, B and Zhao, M and Lu, Q}, title = {Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103058}, doi = {10.1016/j.jaut.2023.103058}, pmid = {37179170}, issn = {1095-9157}, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.}, } @article {pmid37179169, year = {2023}, author = {Zhang, B and Zhou, W and Liu, Q and Huang, C and Hu, Z and Zheng, M and Xin, Y and Zhao, M and Lu, Q}, title = {Effects of fecal microbiota transplant on DNA methylation in patients with systemic lupus erythematosus.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103047}, doi = {10.1016/j.jaut.2023.103047}, pmid = {37179169}, issn = {1095-9157}, abstract = {Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by multiple organ damage accompanied by the over-production of autoantibodies. Decreased intestinal flora diversity and disruption of homeostasis have been proven to be associated with pathogenesis of SLE. In previous study, a clinical trial was conducted to verify the safety and effectiveness of fecal microbiota transplantation (FMT) in the treatment of SLE. To explore the mechanism of FMT in the treatment of SLE, we included 14 SLE patients participating in clinical trials, including 8 in responders group (Rs) and 6 in non-responders group (NRs), and collected peripheral blood DNA and serum. We found that the serum of S-adenosylmethionine (SAM), methylation group donor, was upregulated after FMT, accompanied by an increase in genome-wide DNA methylation level in Rs. We further showed that the methylation levels in promoter regions of Interferon-γ (IFN-γ), induced Helicase C Domain Containing Protein 1 (IFIH1), endoplasmic reticulum membrane protein complex 8 (EMC8), and Tripartite motif-containing protein 58 (TRIM58) increased after FMT treatment. On the contrary, there was no significant change in the methylation of IFIH1 promoter region in the NRs after FMT, and the methylation level of IFIH1 in the Rs was significantly higher than that in the NRs at week 0. We included 850 K methylation chip sequencing, combining previous data of metagenomic sequencing, and metabolomic sequencing for multi-omics analysis to discuss the relationship between flora-metabolite-methylation in FMT. Finally, we found that hexanoic acid treatment can up-regulate the global methylation of peripheral blood mononuclear cells in SLE patients. Overall, our results delineate changes in methylation level after FMT treatment of SLE and reveal possible mechanisms of FMT treatment in terms of the recovery of abnormal hypomethylation.}, } @article {pmid37169290, year = {2023}, author = {Gray, AN and DeFilipp, Z}, title = {Fecal Microbiota Transplantation for Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation: Expanding the Horizon into Pediatrics.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2023.05.007}, pmid = {37169290}, issn = {2666-6367}, abstract = {The microbiome plays a vital role in maintaining homeostasis of the intestinal microenvironment and immune response in allogeneic hematopoietic cell transplantation (HCT) recipients. Disruption of the intestinal microbiome has been associated with the development of acute graft-versus-host disease (GVHD) of the lower GI tract and worse survival. Fecal microbiota transplantation (FMT) can achieve clinical responses in refractory GVHD, establishing the promise of microbiome-directed interventions in this population. While most data about microbial changes in HCT recipients have been generated from the adult population, children with refractory GVHD represent an important group that may benefit from FMT. In this review, we first highlight characteristics that distinguish the pediatric intestinal microbiome from adults. Subsequently, we explore multiple clinical factors that warrant careful consideration to optimize the application of FMT and other microbiome-directed therapeutics to children.}, } @article {pmid37168868, year = {2023}, author = {Satish, S and Abu, Y and Gomez, D and Kumar Dutta, R and Roy, S}, title = {HIV, opioid use, and alterations to the gut microbiome: elucidating independent and synergistic effects.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1156862}, pmid = {37168868}, issn = {1664-3224}, abstract = {BACKGROUND: The microbiome is essential to immune development, defense against pathogens, and modulation of inflammation. Microbial dysbiosis has been reported in various diseases including human immunodeficiency virus (HIV) and opioid use disorder (OUD). Notably, people living with HIV (PLWH) have been reported to both have higher rates of OUD and use opioids at higher rates than the general public. Thus, studying gut microbial alterations in people living with HIV and with OUD could elucidate mechanisms pertaining to how these conditions both shape and are shaped by the microbiome. However, to date few studies have investigated how HIV and OUD in combination impact the microbiome.

AIM OF REVIEW: Here, we review previous studies outlining interactions between HIV, opioid use, and microbial dysbiosis and describe attempts to treat this dysbiosis with fecal microbial transplantation, probiotics, and dietary changes.

While the limited number of studies prevent overgeneralizations; accumulating data suggest that HIV and opioid use together induce distinct alterations in the gut microbiome. Among the three existing preclinical studies of HIV and opioid use, two studies reported a decrease in Lachnospiraceae and Ruminococcaceae, and one study reported a decrease in Muribaculaceae in the combined HIV and opioid group relative to HIV-alone, opioid-alone, or control groups. These bacteria are known to modulate immune function, decrease colonic inflammation, and maintain gut epithelial barrier integrity in healthy individuals. Accordingly, modulation of the gut microbiome to restore gut homeostasis may be attempted to improve both conditions. While mixed results exist regarding treating dysbiosis with microbial restoration in PLWH or in those with opioid dependency, larger well-defined studies that can improve microbial engraftment in hosts hold much promise and should still be explored.}, } @article {pmid37167953, year = {2023}, author = {Porcari, S and Benech, N and Valles-Colomer, M and Segata, N and Gasbarrini, A and Cammarota, G and Sokol, H and Ianiro, G}, title = {Key determinants of success in fecal microbiota transplantation: From microbiome to clinic.}, journal = {Cell host & microbe}, volume = {31}, number = {5}, pages = {712-733}, doi = {10.1016/j.chom.2023.03.020}, pmid = {37167953}, issn = {1934-6069}, abstract = {Fecal microbiota transplantation (FMT) has achieved satisfactory results in preventing the recurrence of Clostridioides difficile infection, but these positive outcomes have only been partially replicated in other diseases. Several factors influence FMT success, including those related to donors and recipients (including diversity and specific composition of the gut microbiome, immune system, and host genetics) as well as to working protocols (fecal amount and number of infusions, route of delivery, and adjuvant treatments). Moreover, initial evidence suggests that the clinical success of FMT may be related to the degree of donor microbial engraftment. The application of cutting-edge technologies for microbiome assessment, along with changes in the current vision of fecal transplants, are expected to improve FMT protocols and outcomes. Here, we review the key determinants of FMT success and insights and strategies that will enable a close integration of lab-based and clinical approaches for increasing FMT success.}, } @article {pmid37167952, year = {2023}, author = {Yadegar, A and Pakpoor, S and Ibrahim, FF and Nabavi-Rad, A and Cook, L and Walter, J and Seekatz, AM and Wong, K and Monaghan, TM and Kao, D}, title = {Beneficial effects of fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {Cell host & microbe}, volume = {31}, number = {5}, pages = {695-711}, doi = {10.1016/j.chom.2023.03.019}, pmid = {37167952}, issn = {1934-6069}, abstract = {Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI). However, the mechanisms underpinning its clinical efficacy are incompletely understood. Herein, we provide an overview of rCDI pathogenesis followed by a discussion of potential mechanisms of action focusing on the current understanding of trans-kingdom microbial, metabolic, immunological, and epigenetic mechanisms. We then outline the current research gaps and offer methodological recommendations for future studies to elevate the quality of research and advance knowledge translation. By combining interventional trials with multiomics technology and host and environmental factors, analyzing longitudinally collected biospecimens will generate results that can be validated with animal and other models. Collectively, this will confirm causality and improve translation, ultimately to develop targeted therapies to replace FMT.}, } @article {pmid37166426, year = {2023}, author = {Cheng, CH and Liu, YC and Yang, YSH and Lin, KJ and Wu, D and Liu, YR and Chang, CC and Hong, CT and Hu, CJ}, title = {Plasmon-activated water as a therapeutic strategy in Alzheimer's disease by altering gut microbiota.}, journal = {Aging}, volume = {15}, number = {}, pages = {}, doi = {10.18632/aging.204706}, pmid = {37166426}, issn = {1945-4589}, abstract = {Gut microbiota (GM) are involved in the pathophysiology of Alzheimer's disease (AD) and might correlate to the machinery of the gut-brain axis. Alteration of the GM profiles becomes a potential therapy strategy in AD. Here, we found that plasmon-activated water (PAW) therapy altered GM profile and reduced AD symptoms in APPswe/PS1dE9 transgenic mice (AD mice). GM profile showed the difference between AD and WT mice. PAW therapy in AD mice altered GM profile and fecal microbiota transplantation (FMT) reproduced GM profile in AD mice. PAW therapy and FMT in AD mice reduced cognitive decline and amyloid accumulation by novel object recognition (NOR) test and amyloid PET imaging. Immunofluorescent staining and western blot analysis of β-amyloid (Aβ) and phosphorylated (p)-tau in the brain of AD mice were reduced in PAW therapy and FMT. The inflammatory markers, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and pro-inflammatory indicator of arginase-1/CD86 ratio were also reduced. Furthermore, immunohistochemistry (IHC) analysis of occludin and claudin-5 in the intestine and AXL in the brain were increased to correlate with the abundant GM in PAW therapy and FMT. Our results showed the machinery of gut-brain axis, and PAW might be a potential therapeutic strategy in AD.}, } @article {pmid37166218, year = {2023}, author = {Li, H and Li, Y and Qian, J}, title = {What is the "optimal formula" for donor selection and feces processing for fecal microbiota transplantation in ulcerative colitis?.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {37166218}, issn = {2542-5641}, } @article {pmid37164760, year = {2023}, author = {Lim, EY and Song, EJ and Shin, HS}, title = {Gut Microbiome as a Possible Cause of Occurrence and Therapeutic Target in Chronic Obstructive Pulmonary Disease.}, journal = {Journal of microbiology and biotechnology}, volume = {33}, number = {8}, pages = {1-8}, doi = {10.4014/jmb.2301.01033}, pmid = {37164760}, issn = {1738-8872}, abstract = {As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.}, } @article {pmid37163080, year = {2023}, author = {Sadler, KE and Atkinson, SN and Ehlers, VL and Waltz, TB and Hayward, M and Rodríguez García, DM and Salzman, NH and Stucky, CL and Brandow, AM}, title = {Gut microbiota and metabolites drive chronic sickle cell disease pain.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.04.25.538342}, pmid = {37163080}, abstract = {UNLABELLED: Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain. In parallel patient and mouse analyses, we identified bilirubin as one metabolite that induces sickle cell pain by altering vagus nerve activity. Furthermore, we determined that decreased abundance of the gut bacteria Akkermansia mucinophila is a critical driver of chronic sickle cell pain. These experiments demonstrate that the sickle cell gut microbiome drives chronic widespread pain and identify bacterial species and metabolites that should be targeted for chronic sickle cell disease pain management.

ONE-SENTENCE SUMMARY: Gut microbes and metabolites drive chronic sickle cell disease pain by altering vagus nerve activity.}, } @article {pmid37162960, year = {2023}, author = {Carr, A and Baliga, NS and Diener, C and Gibbons, SM}, title = {Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.04.28.538771}, pmid = {37162960}, abstract = {Clostridioides difficile colonizes up to 30-40% of community-dwelling adults without causing disease [1, 2] . C. difficile infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S. [3, 4] and typically develop in individuals following disruption of the gut microbiota due to antibiotic or chemotherapy treatments [2] . Further treatment of CDI with antibiotics is not always effective and can lead to antibiotic resistance and recurrent infections (rCDI) [5, 6] . The most effective treatment for rCDI is the reestablishment of an intact microbiota via fecal microbiota transplants (FMTs) [7] . However, the success of FMTs has been difficult to generalize because the microbial interactions that prevent engraftment and facilitate the successful clearance of C. difficile are still only partially understood [8] . Here we show how microbial community-scale metabolic models (MCMMs) accurately predicted known instances of C. difficile colonization susceptibility or resistance. MCMMs provide detailed mechanistic insights into the ecological interactions that govern C. difficile engraftment, like cross-feeding or competition involving metabolites like succinate, trehalose, and ornithine, which differ from person to person. Indeed, three distinct C. difficile metabolic niches emerge from our MCMMs, two associated with positive growth rates and one that represents non-growth, which are consistently observed across 14,862 individuals from four independent cohorts. Finally, we show how MCMMs can predict personalized engraftment and C. difficile growth suppression for a probiotic cocktail (VE303) designed to replace FMTs for the treatment rCDI [9, 10] . Overall, this powerful modeling approach predicts personalized C. difficile engraftment risk and can be leveraged to assess probiotic treatment efficacy. MCMMs could be extended to better understand personalized engraftment of other opportunistic bacterial pathogens, beneficial probiotic organisms, or more complex microbial consortia.}, } @article {pmid37162338, year = {2023}, author = {Naz, F and Petri, WA}, title = {Host Immunity and Immunization Strategies for Clostridioides difficile Infection.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0015722}, doi = {10.1128/cmr.00157-22}, pmid = {37162338}, issn = {1098-6618}, abstract = {Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.}, } @article {pmid37161478, year = {2023}, author = {Raeisi, H and Noori, M and Azimirad, M and Mohebbi, SR and Asadzadeh Aghdaei, H and Yadegar, A and Zali, MR}, title = {Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives.}, journal = {Gut pathogens}, volume = {15}, number = {1}, pages = {21}, pmid = {37161478}, issn = {1757-4749}, abstract = {Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.}, } @article {pmid37160898, year = {2023}, author = {Pang, J and Raka, F and Heirali, AA and Shao, W and Liu, D and Gu, J and Feng, JN and Mineo, C and Shaul, PW and Qian, X and Coburn, B and Adeli, K and Ling, W and Jin, T}, title = {Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {2656}, pmid = {37160898}, issn = {2041-1723}, abstract = {Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1[-/-] mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation.}, } @article {pmid37158970, year = {2023}, author = {Hu, J and Chen, J and Xu, X and Hou, Q and Ren, J and Yan, X}, title = {Gut microbiota-derived 3-phenylpropionic acid promotes intestinal epithelial barrier function via AhR signaling.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {102}, pmid = {37158970}, issn = {2049-2618}, abstract = {BACKGROUND: The intestinal epithelial barrier confers protection against the intestinal invasion by pathogens and exposure to food antigens and toxins. Growing studies have linked the gut microbiota to the intestinal epithelial barrier function. The mining of the gut microbes that facilitate the function of intestinal epithelial barrier is urgently needed.

RESULTS: Here, we studied a landscape of the gut microbiome of seven pig breeds using metagenomics and 16S rDNA gene amplicon sequencing. The results indicated an obvious difference in the gut microbiome between Congjiang miniature (CM) pigs (a native Chinese breed) and commercial Duroc × [Landrace × Yorkshire] (DLY) pigs. CM finishing pigs had stronger intestinal epithelial barrier function than the DLY finishing pigs. Fecal microbiota transplantation from CM and DLY finishing pigs to germ-free (GF) mice transferred the intestinal epithelial barrier characteristics. By comparing the gut microbiome of the recipient GF mice, we identified and validated Bacteroides fragilis as a microbial species that contributes to the intestinal epithelial barrier. B. fragilis-derived 3-phenylpropionic acid metabolite had an important function on the enhancement of intestinal epithelial barrier. Furthermore, 3-phenylpropionic acid facilitated the intestinal epithelial barrier by activating aryl hydrocarbon receptor (AhR) signaling.

CONCLUSIONS: These findings suggest that manipulation of B. fragilis and 3-phenylpropionic acid is a promising strategy for improving intestinal epithelial barrier. Video Abstract.}, } @article {pmid37156115, year = {2023}, author = {Liu, Y and Xu, L and Yang, Z and Wang, D and Li, T and Yang, F and Li, Z and Bai, X and Wang, Y}, title = {Gut-muscle axis and sepsis-induced myopathy: The potential role of gut microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {163}, number = {}, pages = {114837}, doi = {10.1016/j.biopha.2023.114837}, pmid = {37156115}, issn = {1950-6007}, abstract = {Sepsis is described as an immune response disorder of the host to infection in which microorganisms play a non-negligible role. Most survivors of sepsis experience ICU-acquired weakness, also known as septic myopathy, characterized by skeletal muscle atrophy, weakness, and irreparable damage/regenerated or dysfunctional. The mechanism of sepsis-induced myopathy is currently unclear. It has been believed that this state is triggered by circulating pathogens and their related harmful factors, leading to impaired muscle metabolism. Sepsis and its resulting alterations in the intestinal microbiota are associated with sepsis-related organ dysfunction, including skeletal muscle wasting. There are also some studies on interventions targeting the flora, including fecal microbiota transplants, the addition of dietary fiber and probiotics in enteral feeding products, etc., aiming to improve sepsis-related myopathy. In this review, we critically assess the potential mechanisms and therapeutic prospects of intestinal flora in the development of septic myopathy.}, } @article {pmid37154595, year = {2023}, author = {Long, J and Feng, Z and Zhou, H and Liu, J and Zhang, J and Ouyang, J}, title = {Assessing the Relationship Between Gut Microbiota and Posttransplant Diabetes Mellitus.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {21}, number = {4}, pages = {350-360}, doi = {10.6002/ect.2022.0366}, pmid = {37154595}, issn = {2146-8427}, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; *Kidney Transplantation/adverse effects ; *Diabetes Mellitus/diagnosis/etiology ; }, abstract = {OBJECTIVES: The incidence of diabetes significantly increases after kidney transplant, and the associated gut microbiota are closely related to diabetes. However, the gut microbiota of recipients with diabetes after kidney transplant remain unexplored.

MATERIALS AND METHODS: Feces samples from recipients with diabetes 3 months after kidney transplant were collected and analyzed using high-throughput 16S rRNA gene sequencing.

RESULTS: Our study included 45 transplant recipients: 23 posttransplant diabetes mellitus recipients, 11 recipients without diabetes mellitus, and 11 recipients with preexisting diabetes mellitus. No significant differences in intestinal flora richness and α diversity were observed among the 3 groups. However, principal coordinate analysis based on UniFrac distance revealed significant differences in β diversity. At the phyla level, the abundance of Proteobacteria in posttransplant diabetes mellitus recipients decreased (P = .028), whereas that of Bactericide (P = .004) increased. At the class level, the abundance of Gammaproteobacteria (P = .037) decreased, whereas thatofBacteroidia (P=.004)increased.Attheorderlevel, the abundanceof Enterobacteriales (P = .039)decreased, whereasBacteroidales (P=.004)increased.Atthe family level, the abundance of Enterobacteriaceae (P = .039) and Peptostreptococcaceae (P = .008) decreased, whereas Bacteroidaceae (P = .010) increased. At the genus level,the abundance of Lachnospiraceae incertae sedis (P = .008) decreased, whereas Bacteroides (P = .010) increased. Furthermore, KEGG analysis identified 33 pathways, among which the biosynthesis of unsaturated fatty acids was closely related to gut microbiota and posttransplant diabetes mellitus.

CONCLUSIONS: To our knowledge, this is the first comprehensive analysis of the gut microbiota from posttransplant diabetes mellitus recipients. The microbial composition of stool samples of post- transplant diabetes mellitus recipients was significantly different from recipients without diabetes and with preexisting diabetes. The number of bacteria producing short-chain fatty acids decreased, whereas pathogenic bacteria increased.}, } @article {pmid37153213, year = {2023}, author = {Wu, X and Zhao, L and Zhang, Y and Li, K and Yang, J}, title = {The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1166685}, pmid = {37153213}, issn = {1664-042X}, abstract = {Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.}, } @article {pmid37151860, year = {2023}, author = {Galvao, FHF and Araki, J and Fonseca, ABS and Cruz, RJ and Lanchotte, C and Waisberg, DR and Chaib, E and Nacif, LS and Traldi, MCC and de Mello, EB and Andraus, W and Carneiro-D'Albuquerque, L}, title = {Multivisceral transplantation of pelvic organs in rats.}, journal = {Frontiers in surgery}, volume = {10}, number = {}, pages = {1086651}, pmid = {37151860}, issn = {2296-875X}, abstract = {BACKGROUND: Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disorders. Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats.

DONOR OPERATION: We performed a perineal (including the genitalia, anus, muscles, and ligaments) and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian (female), or penile, testis and its ducts (male) was removed en bloc, flushed, and cold-stored.

RECIPIENT OPERATION: The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery.

RESULTS: We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2 h after transplantation.

CONCLUSION: The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%.}, } @article {pmid37151603, year = {2023}, author = {Lv, WJ and Huang, JY and Lin, J and Ma, YM and He, SQ and Zhang, YW and Wang, TZ and Cheng, K and Xiong, Y and Sun, FG and Pan, ZC and Sun, JB and Mao, W and Guo, SN}, title = {Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.}, journal = {Oxidative medicine and cellular longevity}, volume = {2023}, number = {}, pages = {6409385}, pmid = {37151603}, issn = {1942-0994}, abstract = {Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.}, } @article {pmid37150906, year = {2023}, author = {Rasmussen, TS and Mentzel, CMJ and Danielsen, MR and Jakobsen, RR and Zachariassen, LSF and Castro Mejia, JL and Brunse, A and Hansen, LH and Hansen, CHF and Hansen, AK and Nielsen, DS}, title = {Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2208504}, doi = {10.1080/19490976.2023.2208504}, pmid = {37150906}, issn = {1949-0984}, abstract = {Probiotics are intended to improve gastrointestinal health when consumed. However, the probiotics marketed today only colonize the densely populated gut to a limited extent. Bacteriophages comprise the majority of viruses in the human gut virome and there are strong indications that they play important roles in shaping the gut microbiome. Here, we investigate the use of fecal virome transplantation (FVT, sterile filtrated feces) as a mean to alter the gut microbiome composition to lead the way for persistent colonization of two types of probiotics: Lacticaseibacillus rhamnosus GG (LGG) representing a well-established probiotic and Akkermansia muciniphila (AKM) representing a putative next-generation probiotic. Male and female C57BL/6NTac mice were cohoused in pairs from 4 weeks of age and received the following treatment by oral gavage at week 5 and 6: AKM+FVT, LGG+FVT, probiotic sham (Pro-sham)+FVT, LGG+Saline, AKM+Saline, and control (Pro-sham+Saline). The FVT donor material originated from mice with high relative abundance of A. muciniphila. All animals were terminated at age 9 weeks. The FVT treatment did not increase the relative abundance of the administered LGG or AKM in the recipient mice. Instead FVT significantly (p < 0.05) increased the abundance of naturally occurring A. muciniphila compared to the control. This highlights the potential of propagating the existing commensal "probiotics" that have already permanently colonized the gut. Being co-housed male and female, a fraction of the female mice became pregnant. Unexpectedly, the FVT treated mice were found to have a significantly (p < 0.05) higher fertility rate independent of probiotic administration. These preliminary observations urge for follow-up studies investigating interactions between the gut microbiome and fertility.}, } @article {pmid37150800, year = {2023}, author = {Emile, SH and Khan, SM and Garoufalia, Z and Silva-Alvarenga, E and Gefen, R and Horesh, N and Freund, MR and Wexner, SD}, title = {A network meta-analysis of surgical treatments of complete rectal prolapse.}, journal = {Techniques in coloproctology}, volume = {}, number = {}, pages = {}, pmid = {37150800}, issn = {1128-045X}, abstract = {PURPOSE: Surgical treatment of complete rectal prolapse can be undertaken via an abdominal or a perineal approach. The present network meta-analysis aimed to compare the outcomes of different abdominal and perineal procedures for rectal prolapse in terms of recurrence, complications, and improvement in fecal incontinence (FI).

METHODS: A PRISMA-compliant systematic review of PubMed, Scopus, and Web of Science was conducted. Randomized clinical trials comparing two or more procedures for the treatment of complete rectal prolapse were included. The risk of bias was assessed using the ROB-2 tool. The main outcomes were recurrence of full-thickness rectal prolapse, complications, operation time, and improvement in FI.

RESULTS: Nine randomized controlled trials with 728 patients were included. The follow-up ranged between 12 and 47 months. Posterior mesh rectopexy had significantly lower odds of recurrence than did the Altemeier procedure (logOR, - 12.75;  95% credible intervals, - 40.91, - 1.75), Delorme procedure (- 13.10; - 41.26, - 2.09), resection rectopexy (- 11.98; - 41.36, - 0.19), sponge rectopexy (- 13.19; - 42.87, - 0.54), and sutured rectopexy (- 13.12; - 42.58, - 1.50), but similar odds to ventral mesh rectopexy (- 12.09; - 41.7, 0.03). Differences among the procedures in complications, operation time, and improvement in FI were not significant.

CONCLUSIONS: Posterior mesh rectopexy ranked best with the lowest recurrence while perineal procedures ranked worst with the highest recurrence rates.}, } @article {pmid37150613, year = {2023}, author = {Qasimi, MI and Fukuzawa, S and Suenaga, K and Kambe, J and Li, C and Tomonaga, S and Kawase, T and Tsukahara, T and Hirayama, K and Inoue, R and Yamamoto, Y and Nagaoka, K}, title = {L-amino acid oxidase-1 is involved in the gut-liver axis by regulating 5-aminolevulinic acid production in mice.}, journal = {The Journal of veterinary medical science}, volume = {}, number = {}, pages = {}, doi = {10.1292/jvms.23-0080}, pmid = {37150613}, issn = {1347-7439}, abstract = {L-amino acid oxidase (LAAO) is a metabolic enzyme that converts L-amino acids into ketoacids, ammonia, and hydrogen peroxide (H2O2). The generated H2O2 has previously been shown to have antibacterial and gut microbiota-modulatory properties in LAO1 knock-out (KO) mice. Since most microbial metabolites reach the liver through the portal vein, we examined gut-liver interactions in LAO1 KO mice. We found lower total cholesterol levels, higher glutamic pyruvic transaminase (GPT) levels in the serum, and higher pro-inflammatory cytokine mRNA expression in the liver tissue. In wild-type (WT) mice, LAO1 was expressed in gut tissues (ileum and colon). Microbiome analysis revealed that the abundance of some bacteria was altered in LAO1 KO mice. However, short-chain fatty acid (SCFAs) levels in cecal feces and gut permeability did not change. Fecal microbiota transplantation (FMT) revealed that feces from LAO1 KO mice slightly stimulated pro-inflammatory cytokine expression in the liver. During metabolomic analysis, 5-Aminolevulinic acid (5-ALA) was the only metabolite found to be significantly upregulated in the portal and abdominal veins of the LAO1 KO mice. Intraperitoneal administration of 5-ALA to WT mice significantly increased IL-6 mRNA expression in the liver. These observations suggest that gut LAO1 plays a role in regulating 5-ALA production and that a high level of 5-ALA stimulates the liver to increase pro-inflammatory cytokine expression by disrupting LAO1 in mice.}, } @article {pmid37150070, year = {2023}, author = {Chernova, VO and Terveer, EM and van Prehn, J and Kuijper, EJ and Keller, JJ and van der Meulen-de Jong, AE and Bauer, MP and van Hilten, JJ and Contarino, MF}, title = {Fecal microbiota transplantation for Parkinson's disease using levodopa - carbidopa intestinal gel percutaneous endoscopic gastro-jejeunal tube.}, journal = {Parkinsonism & related disorders}, volume = {111}, number = {}, pages = {105410}, doi = {10.1016/j.parkreldis.2023.105410}, pmid = {37150070}, issn = {1873-5126}, abstract = {We report a patient with a 5-year diagnosis of akinetic-rigid Parkinson's disease under treatment with Levodopa-Carbidopa Intestinal Gel therapy through a PEG-J tube due to motor complications, in which, in the context of a clinical study, we successfully and safely administered fecal microbiota transplant through a PEG-J.}, } @article {pmid37147692, year = {2023}, author = {An, Y and Dai, H and Duan, Y and Cheng, L and Shi, L and He, C and Wang, C and Lv, Y and Li, H and Zhang, H and Huang, Y and Fu, W and Sun, W and Zhao, B}, title = {The relationship between gut microbiota and susceptibility to type 2 diabetes mellitus in rats.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {49}, pmid = {37147692}, issn = {1749-8546}, abstract = {PURPOSE: The purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.

METHODS: Thirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.

RESULTS: G__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.

CONCLUSIONS: G__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.}, } @article {pmid37147641, year = {2023}, author = {Zhang, Y and Liu, L and Wei, C and Wang, X and Li, R and Xu, X and Zhang, Y and Geng, G and Dang, K and Ming, Z and Tao, X and Xu, H and Yan, X and Zhang, J and Hu, J and Li, Y}, title = {Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {174}, pmid = {37147641}, issn = {1741-7015}, abstract = {BACKGROUND: There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention.

METHODS: We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.

RESULTS: After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.

CONCLUSIONS: Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.

TRIAL REGISTRATION: The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).}, } @article {pmid37146560, year = {2023}, author = {Kani, K and Kasai, K and Tada, Y and Ishibashi, R and Takano, S and Igarashi, N and Ichimura-Shimizu, M and Tsuneyama, K and Furusawa, Y and Nagai, Y}, title = {The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.}, journal = {Biochemical and biophysical research communications}, volume = {664}, number = {}, pages = {77-85}, doi = {10.1016/j.bbrc.2023.04.068}, pmid = {37146560}, issn = {1090-2104}, abstract = {Radioprotective 105 (RP105) plays a key role in the development of high-fat diet (HFD)-induced metabolic disorders; however, the underlying mechanisms remain to be understood. Here, we aimed to uncover whether RP105 affects metabolic syndrome through the modification of gut microbiota. We confirmed that body weight gain and fat accumulation by HFD feeding were suppressed in Rp105[-/-] mice. Fecal microbiome transplantation from HFD-fed donor Rp105[-/-] mice into HFD-fed recipient wild-type mice significantly improved various abnormalities associated with metabolic syndrome, including body weight gain, insulin resistance, hepatic steatosis, macrophage infiltration and inflammation in the adipose tissue. In addition, HFD-induced intestinal barrier dysfunction was attenuated by fecal microbiome transplantation from HFD-fed donor Rp105[-/-] mice. A 16S rRNA sequence analysis indicated that RP105 modified gut microbiota composition and was involved in the maintenance of its diversity. Thus, RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.}, } @article {pmid37145345, year = {2023}, author = {Sha, H and He, X and Yan, K and Li, J and Li, X and Xie, Y and Yang, Y and Deng, Y and Li, G and Yang, J}, title = {Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {}, number = {}, pages = {}, doi = {10.1111/apm.13326}, pmid = {37145345}, issn = {1600-0463}, abstract = {Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self-reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive-like behaviors and mood-related indicators, and inflammation, verified by the increased levels of the pro-inflammatory cytokine, in coprophagy-blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease-like phenotypes in the coprophagy-blocked group were worse than those in the coprophagy-unblocked group, including severer depressive symptoms and higher levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.}, } @article {pmid37145326, year = {2023}, author = {Sha, S and Zeng, H and Gao, H and Shi, H and Quan, X and Chen, F and Liu, M and Xu, B and Liu, X}, title = {Adherent-invasive Escherichia coli LF82 aggravated intestinal inflammation in colitis mice by affecting the gut microbiota and Th17/Treg cell differentiation balance.}, journal = {Archives of microbiology}, volume = {205}, number = {6}, pages = {218}, pmid = {37145326}, issn = {1432-072X}, abstract = {The imbalance of Th17 and Treg cell differentiation, intestinal flora imbalance, and intestinal mucosal barrier damage may be important links in the occurrence and development of inflammatory bowel disease (IBD) since Th17 and Treg differentiation are affected by the intestinal flora. This study aimed to explore the effect of Escherichia coli (E. coli) LF82 on the differentiation of Th17 and Treg cells and the role of the intestinal flora in mouse colitis. The effects of E. coli LF82 infection on intestinal inflammation were evaluated by analyzing the disease activity index, histology, myeloperoxidase activity, FITC-D fluorescence value, and claudin-1 and ZO-1 expression. The effects of E. coli LF82 on the Th17/Treg balance and intestinal flora were analyzed by flow cytometry and 16S rDNA sequencing. Inflammatory markers, changes in the intestinal flora, and Th17/Treg cells were then detected after transplanting fecal bacteria from normal mice into colitis mice infected by E. coli LF82. We found that E. coli LF82 infection can aggravate the intestinal inflammation of mice colitis, destroy their intestinal mucosal barrier, increase intestinal mucosal permeability, and aggravate the imbalance of Th17/Treg differentiation and the disorder of intestinal flora. After improving the intestinal flora imbalance by fecal bacteria transplantation, intestinal inflammation and intestinal mucosal barrier damage were reduced, and the differentiation balance of Th17 and Treg cells was restored. This study showed that E. coli LF82 infection aggravates intestinal inflammation and intestinal mucosal barrier damage in colitis by affecting the intestinal flora composition and indirectly regulating the Th17 and Treg cell differentiation balance.}, } @article {pmid37143538, year = {2023}, author = {Yu, H and Li, XX and Han, X and Chen, BX and Zhang, XH and Gao, S and Xu, DQ and Wang, Y and Gao, ZK and Yu, L and Zhu, SL and Yao, LC and Liu, GR and Liu, SL and Mu, XQ}, title = {Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1126808}, pmid = {37143538}, issn = {1664-302X}, abstract = {Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8[+] T and CD49b[+] NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3[+] Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.}, } @article {pmid37143119, year = {2023}, author = {Li, S and Zheng, J and He, J and Liu, H and Huang, Y and Huang, L and Wang, K and Zhao, X and Feng, B and Che, L and Fang, Z and Li, J and Xu, S and Lin, Y and Jiang, X and Hua, L and Zhuo, Y and Wu, D}, title = {Dietary fiber during gestation improves lactational feed intake of sows by modulating gut microbiota.}, journal = {Journal of animal science and biotechnology}, volume = {14}, number = {1}, pages = {65}, pmid = {37143119}, issn = {1674-9782}, abstract = {BACKGROUND: The feed intake of sows during lactation is often lower than their needs. High-fiber feed is usually used during gestation to increase the voluntary feed intake of sows during lactation. However, the mechanism underlying the effect of bulky diets on the appetites of sows during lactation have not been fully clarified. The current study was conducted to determine whether a high-fiber diet during gestation improves lactational feed intake (LFI) of sows by modulating gut microbiota.

METHODS: We selected an appropriate high-fiber diet during gestation and utilized the fecal microbial transplantation (FMT) method to conduct research on the role of the gut microbiota in feed intake regulation of sows during lactation, as follows: high-fiber (HF) diet during gestation (n = 23), low-fiber (LF) diet during gestation (n = 23), and low-fiber diet + HF-FMT (LFM) during gestation (n = 23).

RESULTS: Compared with the LF, sows in the HF and LFM groups had a higher LFI, while the sows also had higher peptide tyrosine tyrosine and glucagon-like peptide 1 on d 110 of gestation (G110 d). The litter weight gain of piglets during lactation and weaning weight of piglets from LFM group were higher than LF group. Sows given a HF diet had lower Proteobacteria, especially Escherichia-Shigella, on G110 d and higher Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus, on d 7 of lactation (L7 d). The abundance of Escherichia-Shigella was reduced by HF-FMT in numerically compared with the LF. In addition, HF and HF-FMT both decreased the perinatal concentrations of proinflammatory factors, such as endotoxin (ET), lipocalin-2 (LCN-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). The concentration of ET and LCN-2 and the abundance of Proteobacteria and Escherichia-Shigella were negatively correlated with the LFI of sows.

CONCLUSION: The high abundance of Proteobacteria, especially Escherichia-Shigella of LF sows in late gestation, led to increased endotoxin levels, which result in inflammatory responses and adverse effects on the LFI of sows. Adding HF during gestation reverses this process by increasing the abundance of Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus.}, } @article {pmid37142392, year = {2023}, author = {Ng, RW and Dharmaratne, P and Wong, S and Hawkey, P and Chan, P and Ip, M}, title = {Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): a systematic review.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2023-329515}, pmid = {37142392}, issn = {1468-3288}, } @article {pmid37138170, year = {2023}, author = {Zhou, S and Yu, J}, title = {Crohn's disease and breast cancer: a literature review of the mechanisms and treatment.}, journal = {Internal and emergency medicine}, volume = {}, number = {}, pages = {}, pmid = {37138170}, issn = {1970-9366}, abstract = {This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.}, } @article {pmid37138075, year = {2023}, author = {Park, JS and Gazzaniga, FS and Wu, M and Luthens, AK and Gillis, J and Zheng, W and LaFleur, MW and Johnson, SB and Morad, G and Park, EM and Zhou, Y and Watowich, SS and Wargo, JA and Freeman, GJ and Kasper, DL and Sharpe, AH}, title = {Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {37138075}, issn = {1476-4687}, abstract = {The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice[1-6]. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma[7,8]. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and PD-L2 share PD-1 as a binding partner, but PD-L2 can also bind RGMb. We demonstrate that blockade of PD-L2-RGMb interactions can overcome microbiome-dependent resistance to PD-1 pathway inhibitors. Antibody-mediated blockade of the PD-L2-RGMb pathway or conditional deletion of RGMb in T cells combined with an anti-PD-1 or anti-PD-L1 antibody promotes anti-tumour responses in multiple mouse tumour models that do not respond to anti-PD-1 or anti-PD-L1 alone (germ-free mice, antibiotic-treated mice and even mice colonized with stool samples from a patient who did not respond to treatment). These studies identify downregulation of the PD-L2-RGMb pathway as a specific mechanism by which the gut microbiota can promote responses to PD-1 checkpoint blockade. The results also define a potentially effective immunological strategy for treating patients who do not respond to PD-1 cancer immunotherapy.}, } @article {pmid37132118, year = {2023}, author = {Okamura, T and Hamaguchi, M and Nakajima, H and Kitagawa, N and Majima, S and Senmaru, T and Okada, H and Ushigome, E and Nakanishi, N and Sasano, R and Fukui, M}, title = {Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcsm.13245}, pmid = {37132118}, issn = {2190-6009}, abstract = {BACKGROUND: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice.

METHODS: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8 weeks and fed milk (100 μL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age.

RESULTS: Milk administration to db/db mice increased grip strength (Milk-: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk-: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk-: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk-: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk.

CONCLUSIONS: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.}, } @article {pmid37130682, year = {2023}, author = {Dougé, A and Ravinet, A and Corriger, A and Cabrespine, A and Wasiak, M and Pereira, B and Sokol, H and Nguyen, S and Bay, JO}, title = {Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological malignancies: a study protocol for a randomised controlled phase-II trial (the FMT-allo study).}, journal = {BMJ open}, volume = {13}, number = {5}, pages = {e068480}, doi = {10.1136/bmjopen-2022-068480}, pmid = {37130682}, issn = {2044-6055}, abstract = {INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis.

METHODS AND ANALYSIS: This prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming's single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1 year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld's test and by plotting residuals.

ETHICS AND DISSEMINATION: The local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses.

TRIAL REGISTRATION NUMBER: NCT04935684.}, } @article {pmid37125201, year = {2023}, author = {Xu, H and Xu, Z and Long, S and Li, Z and Jiang, J and Zhou, Q and Huang, X and Wu, X and Wei, W and Li, X}, title = {The role of the gut microbiome and its metabolites in cerebrovascular diseases.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1097148}, pmid = {37125201}, issn = {1664-302X}, abstract = {The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.}, } @article {pmid37125159, year = {2023}, author = {Kong, CY and Yang, YQ and Han, B and Chen, HL and Mao, YQ and Huang, JT and Wang, LS and Li, ZM}, title = {Fecal microbiome transplant from patients with lactation mastitis promotes mastitis in conventional lactating mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1123444}, pmid = {37125159}, issn = {1664-302X}, abstract = {INTRODUCTION: Lactation mastitis seriously severely affects the health of lactating females and their infants, yet the underlying causes of clinical lactation mastitis remain unclear.

METHODS: In this study, we used microbiota-humanized mice as a model to investigate the role of gut microbiota in lactation mastitis. We compared the fecal microbiota of lactation mastitis patients and healthy individuals and conducted fecal microbiota transplantation (FMT) experiments in an antibiotic-pretreated mouse model to test whether gut microbes contribute to human lactation mastitis.

RESULTS: Our results showed that gut microbiota diversity was reduced and dysbiosis was present in lactating mastitis patients. FMT from lactation mastitis patients (M-FMT), but not from healthy individuals (H-FMT), to antibiotic-treated mice resulted in lactation mastitis. The inflammation in mice caused by gut microbiota from lactating mastitis patients appears to be pervasive, as hepatocytes from mice that received feces from lactating mastitis patients showed marked swelling. In addition, serum pro-inflammatory factors, including IL-4, IL-17, MPO, IL-6, IL-1β, and TNF-α, were significantly increased in the M-FMT group. The Firmicutes/Bacteroidetes ratio (F/B), a biomarker of gut dysbiosis, was significantly increased in the M-FMT group. At the phylum level, Actinobacteria were significantly increased, and Verrucomicrobia were significantly decreased in the M-FMT group. At the genus level, Ruminococcus and Faecalibacterium were significantly reduced, while Parabacteroides were significantly increased in the feces of both patients with lactation mastitis and M-FMT mice. Moreover, our study revealed an "amplification effect" on microbiota differences and mastitis disease following human-to-mouse FMT.

CONCLUSION: Collectively, our findings demonstrate that the gut microbiota in lactating mastitis patients is dysbiotic and contributes to the pathogenesis of mastitis.}, } @article {pmid37122756, year = {2023}, author = {Dong, Y and Zhang, K and Wei, J and Ding, Y and Wang, X and Hou, H and Wu, J and Liu, T and Wang, B and Cao, H}, title = {Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1158200}, pmid = {37122756}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes ; Fatty Acids, Volatile ; Butyrates/therapeutic use ; *Gastrointestinal Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Tumor immune microenvironment (TIME), a tumor-derived immune component, is proven to be closely related to the development, metastasis, and recurrence of tumors. Gut microbiota and its fermented-metabolites short-chain fatty acids (SCFAs) play a critical role in maintaining the immune homeostasis of gastrointestinal tumors. Consisting mainly of acetate, propionate, and butyrate, SCFAs can interact with G protein-coupled receptors 43 of T helper 1 cell or restrain histone deacetylases (HDACs) of cytotoxic T lymphocytes to exert immunotherapy effects. Studies have shed light on SCFAs can mediate the differentiation and function of regulatory T cells, as well as cytokine production in TIME. Additionally, SCFAs can alter epigenetic modification of CD8[+] T cells by inhibiting HDACs to participate in the immune response process. In gastrointestinal tumors, the abundance of SCFAs and their producing bacteria is significantly reduced. Direct supplementation of dietary fiber and probiotics, or fecal microbiota transplantation to change the structure of gut microbiota can both increase the level of SCFAs and inhibit tumor development. The mechanism by which SCFAs modulate the progression of gastrointestinal tumors has been elucidated in this review, aiming to provide prospects for the development of novel immunotherapeutic strategies.}, } @article {pmid37117118, year = {2023}, author = {Yang, R and Chen, Z and Cai, J}, title = {Fecal microbiota transplantation: Emerging applications in autoimmune diseases.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103038}, doi = {10.1016/j.jaut.2023.103038}, pmid = {37117118}, issn = {1095-9157}, abstract = {Both genetic susceptibility and environmental factors are important contributors to autoimmune disease pathogenesis. As an environmental factor, the gut microbiome plays a crucial role in the development and progression of autoimmune diseases. Thus, strategies targeting gut microbiome alterations can potentially be used to treat autoimmune disease. Microbiota-based interventions, such as prebiotics, probiotics, dietary interventions, and fecal microbiota transplantation (FMT), have attracted growing interest as novel treatment approaches. FMT is an effective method for treating recurrent Clostridioides difficile infections; moreover, it is emerging as a promising treatment for patients with inflammatory bowel disease and other autoimmune diseases. Although the mechanisms underpinning the interaction between the gut microbiome and host are not fully understood in patients with autoimmune disease, FMT has been shown to restore altered gut microbiota composition, rebuild the intestinal microecosystem, and mediate innate and adaptive immune responses to achieve a therapeutic effect. In this review, we provide an overview of FMT and discuss how FMT can be used as a novel treatment approach for autoimmune diseases. Furthermore, we discuss recent challenges and offer future research directions.}, } @article {pmid37117525, year = {2021}, author = {Mossad, O and Nent, E and Woltemate, S and Folschweiller, S and Buescher, JM and Schnepf, D and Erny, D and Staeheli, P and Bartos, M and Szalay, A and Stecher, B and Vital, M and Sauer, JF and Lämmermann, T and Prinz, M and Blank, T}, title = {Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline.}, journal = {Nature aging}, volume = {1}, number = {12}, pages = {1127-1136}, pmid = {37117525}, issn = {2662-8465}, mesh = {Animals ; Mice ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology ; Cognition/physiology ; *Cognitive Dysfunction/metabolism ; Brain/metabolism ; }, abstract = {Understanding the physiological origins of age-related cognitive decline is of critical importance given the rising age of the world's population[1]. Previous work in animal models has established a strong link between cognitive performance and the microbiota[2-5], and it is known that the microbiome undergoes profound remodeling in older adults[6]. Despite growing evidence for the association between age-related cognitive decline and changes in the gut microbiome, the mechanisms underlying such interactions between the brain and the gut are poorly understood. Here, using fecal microbiota transplantation (FMT), we demonstrate that age-related remodeling of the gut microbiota leads to decline in cognitive function in mice and that this impairment can be rescued by transplantation of microbiota from young animals. Moreover, using a metabolomic approach, we found elevated concentrations of δ-valerobetaine, a gut microbiota-derived metabolite, in the blood and brain of aged mice and older adults. We then demonstrated that δ-valerobetaine is deleterious to learning and memory processes in mice. At the neuronal level, we showed that δ-valerobetaine modulates inhibitory synaptic transmission and neuronal network activity. Finally, we identified specific bacterial taxa that significantly correlate with δ-valerobetaine levels in the brain. Based on our findings, we propose that δ-valerobetaine contributes to microbiota-driven brain aging and that the associated mechanisms represent a promising target for countering age-related cognitive decline.}, } @article {pmid37117767, year = {2021}, author = {Boehme, M and Guzzetta, KE and Bastiaanssen, TFS and van de Wouw, M and Moloney, GM and Gual-Grau, A and Spichak, S and Olavarría-Ramírez, L and Fitzgerald, P and Morillas, E and Ritz, NL and Jaggar, M and Cowan, CSM and Crispie, F and Donoso, F and Halitzki, E and Neto, MC and Sichetti, M and Golubeva, AV and Fitzgerald, RS and Claesson, MJ and Cotter, PD and O'Leary, OF and Dinan, TG and Cryan, JF}, title = {Microbiota from young mice counteracts selective age-associated behavioral deficits.}, journal = {Nature aging}, volume = {1}, number = {8}, pages = {666-676}, pmid = {37117767}, issn = {2662-8465}, abstract = {The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.}, } @article {pmid37116852, year = {2023}, author = {Liu, Y and Chen, LJ and Li, XW and Yang, JZ and Liu, JL and Zhang, KK and Li, JH and Wang, Q and Xu, JT and Zhi, X}, title = {Gut microbiota contribute to Methamphetamine-induced cardiotoxicity in mouse model.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110512}, doi = {10.1016/j.cbi.2023.110512}, pmid = {37116852}, issn = {1872-7786}, abstract = {Methamphetamine (METH) is a psychotropic drug known to cause cardiotoxicity. The gut-heart axis is emerging as an important pathway linking gut microbiota to cardiovascular disease, but the precise association between METH-induced cardiotoxicity and gut microbiota has yet to be elucidated. In this study, we established an escalating dose-multiple METH administration model in male BALB/c mice, examined cardiac injury and gut microbiota, and investigated the contribution of gut microbiota to cardiotoxicity induced by METH. Additionally, we treated mice with antibiotics and fecal microbiota transplantation (FMT) to assess the impact of gut microbiota on cardiotoxicity. Our results showed that METH exposure altered the p53 and PI3K/Akt signaling pathways and modulated the apoptosis pathway in heart tissue, accompanied by elevated levels of Bax/BCL-2 expression and cleaved caspase-3 proteins. METH exposure increased the diversity and richness of gut microbiota, and significantly changed the microbial community composition, accompanied by elevated abundance of Lactobacillus, Bifidobacterium, and decreased abundance of Bacteroides, norank_f_Muribaculaceae and Alistipes. Eliminating gut microbiota by antibiotics treatment alleviated METH-induced cardiotoxicity, while FMT treatment transferred similar cardiac injury manifestations from METH-exposed mice to healthy recipient mice. Our study unveils the crucial involvement of gut microbiota in the development of cardiotoxicity induced by METH and provides potential strategies for treating cardiac complications caused by METH.}, } @article {pmid37114052, year = {2023}, author = {Schroeder, JH and Beattie, G and Lo, JW and Zabinski, T and Powell, N and Neves, JF and Jenner, RG and Lord, GM}, title = {CD90 is not constitutively expressed in functional innate lymphoid cells.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1113735}, pmid = {37114052}, issn = {1664-3224}, abstract = {Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker. CD90-negative and CD90-low CD127[+] ILC were present amongst all ILC subsets in the gut. The frequency of CD90-negative and CD90-low CD127[+] ILC was dependent on stimulatory cues in vitro and enhanced by dysbiosis in vivo. CD90-negative and CD90-low CD127[+] ILC were a potential source of IL-13, IFNγ and IL-17A at steady state and upon dysbiosis- and dextran sulphate sodium-elicited colitis. Hence, this study reveals that, contrary to expectations, CD90 is not constitutively expressed by functional ILC in the gut.}, } @article {pmid37113615, year = {2023}, author = {Lenti, MV and Scribano, ML and Biancone, L and Ciccocioppo, R and Pugliese, D and Pastorelli, L and Fiorino, G and Savarino, E and Caprioli, FA and Ardizzone, S and Fantini, MC and Tontini, GE and Orlando, A and Sampietro, GM and Sturniolo, GC and Monteleone, G and Vecchi, M and Kohn, A and Daperno, M and D'Incà, R and Corazza, GR and Di Sabatino, A}, title = {Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1031998}, pmid = {37113615}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.}, } @article {pmid37113132, year = {2023}, author = {Chen, X and Zhang, W and Lin, Z and Zheng, C and Chen, S and Zhou, H and Liu, Z}, title = {Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1103189}, pmid = {37113132}, issn = {2235-2988}, abstract = {BACKGROUND: Recent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.

OBJECTIVES: This study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.

METHODS: Five patients aged 54-80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.

RESULTS: The MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.

CONCLUSIONS: In this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.}, } @article {pmid37111404, year = {2023}, author = {Sharma, M and Dhaliwal, M and Tyagi, R and Goyal, T and Sharma, S and Rawat, A}, title = {Microbiome and Its Dysbiosis in Inborn Errors of Immunity.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/pathogens12040518}, pmid = {37111404}, issn = {2076-0817}, abstract = {Inborn errors of immunity (IEI) can present with infections, autoimmunity, lymphoproliferation, granulomas, and malignancy. IEIs are due to genetic abnormalities that disrupt normal host-immune response or immune regulation. The microbiome appears essential for maintaining host immunity, especially in patients with a defective immune system. Altered gut microbiota in patients with IEI can lead to clinical symptoms. Microbial dysbiosis is the consequence of an increase in pro-inflammatory bacteria or a reduction in anti-inflammatory bacteria. However, functional and compositional differences in microbiota are also involved. Dysbiosis and a reduced alpha-diversity are well documented, particularly in conditions like common variable immunodeficiency. Deranged microbiota is also seen in Wiskott-Aldrich syndrome, severe combined immunodeficiency, chronic granulomatous disease, selective immunoglobulin-A deficiency, Hyper IgE syndrome (HIGES), X-linked lymphoproliferative disease-2, immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome, and defects of IL10 signalling. Distinct gastrointestinal, respiratory, and cutaneous symptoms linked to dysbiosis are seen in several IEIs, emphasizing the importance of microbiome identification. In this study, we discuss the processes that maintain immunological homeostasis between commensals and the host and the disruptions thereof in patients with IEIs. As the connection between microbiota, host immunity, and infectious illnesses is better understood, microbiota manipulation as a treatment strategy or infection prevention method would be more readily employed. Therefore, optimal prebiotics, probiotics, postbiotics, and fecal microbial transplantation can be promising strategies to restore the microbiota and decrease disease pathology in patients with IEIs.}, } @article {pmid37111321, year = {2023}, author = {Kumar, A and Pramanik, J and Goyal, N and Chauhan, D and Sivamaruthi, BS and Prajapati, BG and Chaiyasut, C}, title = {Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, doi = {10.3390/ph16040565}, pmid = {37111321}, issn = {1424-8247}, abstract = {The gut microbiota is critical for maintaining human health and the immunological system. Several neuroscientific studies have shown the significance of microbiota in developing brain systems. The gut microbiota and the brain are interconnected in a bidirectional relationship, as research on the microbiome-gut-brain axis shows. Significant evidence links anxiety and depression disorders to the community of microbes that live in the gastrointestinal system. Modified diet, fish and omega-3 fatty acid intake, macro- and micro-nutrient intake, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, and 5-HTP regulation may all be utilized to alter the gut microbiota as a treatment approach. There are few preclinical and clinical research studies on the effectiveness and reliability of various therapeutic approaches for depression and anxiety. This article highlights relevant research on the association of gut microbiota with depression and anxiety and the different therapeutic possibilities of gut microbiota modification.}, } @article {pmid37111173, year = {2023}, author = {Zhuang, H and Yang, Z and Chen, T and Jing, N and Zhou, Y and Jiang, G and Wang, Y and Wang, Z and Liu, Z}, title = {Boosting HSA Vaccination with Jujube Powder Modulating Gut Microbiota Favorable for Arginine Metabolism.}, journal = {Nutrients}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/nu15081955}, pmid = {37111173}, issn = {2072-6643}, abstract = {Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.}, } @article {pmid37110500, year = {2023}, author = {Dahiya, M and Jovel, J and Monaghan, T and Wong, K and Elhenawy, W and Chui, L and McAlister, F and Kao, D}, title = {In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {11}, number = {4}, pages = {}, doi = {10.3390/microorganisms11041078}, pmid = {37110500}, issn = {2076-2607}, abstract = {IMPORTANCE: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood.

AIM: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT.

METHODS: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT.

RESULTS: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition.

CONCLUSION: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.}, } @article {pmid37107633, year = {2023}, author = {Benlabidi, S and Raddaoui, A and Lengliz, S and Cheriet, S and Hynds, P and Achour, W and Ghrairi, T and Abbassi, MS}, title = {Occurrence of High-Risk Clonal Lineages ST58, ST69, ST224, and ST410 among Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolated from Healthy Free-Range Chickens (Gallus gallus domesticus) in a Rural Region in Tunisia.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/genes14040875}, pmid = {37107633}, issn = {2073-4425}, abstract = {Antimicrobial-resistant Escherichia coli isolates have emerged in various ecologic compartments and evolved to spread globally. We sought to (1.) investigate the occurrence of ESBL-producing E. coli (ESBL-Ec) in feces from free-range chickens in a rural region and (2.) characterize the genetic background of antimicrobial resistance and the genetic relatedness of collected isolates. Ninety-five feces swabs from free-range chickens associated with two households (House 1/House 2) in a rural region in northern Tunisia were collected. Samples were screened to recover ESBL-Ec, and collected isolates were characterized for phenotype/genotype of antimicrobial resistance, integrons, and molecular typing (pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)). Overall, 47 ESBL-Ec were identified, with the following genes detected: 35 blaCTX-M-1, 5 blaCTX-M-55, 5 blaCTX-M-15, 1 blaSHV-2, and 1 blaSHV-12. Resistance to fluoroquinolones, tetracycline, sulfonamides, and colistin was encoded by aac(6')-Ib-cr (n = 21), qnrB (n = 1), and qnrS (n = 2); tetA (n = 17)/tetB (n = 26); sul1 (n = 29)/sul2 (n = 18); and mcr-2 (n = 2) genes, respectively. PFGE and MLST identified genetic homogeneity of isolates in House 1; however, isolates from House 2 were heterogeneous. Notably, among nine identified sequence types, ST58, ST69, ST224, and ST410 belong to pandemic high-risk clonal lineages associated with extrapathogenic E. coli. Minor clones belonging to ST410 and ST471 were shared by chickens from both households. The virulence genes fyuA, fimH, papGIII, and iutA were detected in 35, 47, 17, and 23 isolates, respectively. Findings indicate a high occurrence of ESBL-Ec in free-range chickens and highlight the occurrence of pandemic zoonotic clones.}, } @article {pmid37106510, year = {2023}, author = {Luo, X and Li, H and Fan, X and Wu, X and Zhou, R and Lei, Y and Xue, D and Yang, F and Xu, Y and Wang, K}, title = {The Gut Microbiota - Brain Axis: Potential Mechanism of Drug Addiction.}, journal = {Current topics in medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/1568026623666230418114133}, pmid = {37106510}, issn = {1873-4294}, abstract = {INTRODUCTION: As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems.

METHOD: These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders.

RESULT: We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders.

CONCLUSION: Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.}, } @article {pmid37106463, year = {2023}, author = {de Wouters d'Oplinter, A and Verce, M and Huwart, SJP and Lessard-Lord, J and Depommier, C and Van Hul, M and Desjardins, Y and Cani, PD and Everard, A}, title = {Obese-associated gut microbes and derived phenolic metabolite as mediators of excessive motivation for food reward.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {94}, pmid = {37106463}, issn = {2049-2618}, abstract = {BACKGROUND: Excessive hedonic consumption is one of the main drivers for weight gain. Identifying contributors of this dysregulation would help to tackle obesity. The gut microbiome is altered during obesity and regulates host metabolism including food intake.

RESULTS: By using fecal material transplantation (FMT) from lean or obese mice into recipient mice, we demonstrated that gut microbes play a role in the regulation of food reward (i.e., wanting and learning processes associated with hedonic food intake) and could be responsible for excessive motivation to obtain sucrose pellets and alterations in dopaminergic and opioid markers in reward-related brain areas. Through untargeted metabolomic approach, we identified the 3-(3'-hydroxyphenyl)propanoic acid (33HPP) as highly positively correlated with the motivation. By administrating 33HPP in mice, we revealed its effects on food reward.

CONCLUSIONS: Our data suggest that targeting the gut microbiota and its metabolites would be an interesting therapeutic strategy for compulsive eating, preventing inappropriate hedonic food intake. Video Abstract.}, } @article {pmid37104445, year = {2023}, author = {Tuniyazi, M and Wang, W and Zhang, N}, title = {A Systematic Review of Current Applications of Fecal Microbiota Transplantation in Horses.}, journal = {Veterinary sciences}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/vetsci10040290}, pmid = {37104445}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) is a technique involving transferring fecal matter from a healthy donor to a recipient, with the goal of reinstating a healthy microbiome in the recipient's gut. FMT has been used in horses to manage various gastrointestinal disorders, such as colitis and diarrhea. To evaluate the current literature on the use of FMT in horses, including its efficacy, safety, and potential applications, the authors conducted an extensive search of several databases, including PubMed, MEDLINE, Web of Science, and Google Scholar, published up to 11 January 2023. The authors identified seven studies that met their inclusion criteria, all of which investigated the FMT application as a treatment for gastrointestinal disorders such as colitis and diarrhea. The authors demonstrated that FMT was generally effective in treating these conditions. However, the authors noted that the quality of the studies was generally suboptimal and characterized by small sample sizes and a lack of control groups. The authors concluded that FMT is a promising treatment option for certain gastrointestinal disorders in horses. Nevertheless, more research is required to determine the optimal donor selection, dosing, and administration protocols, as well as the long-term safety and efficacy of FMT in horses.}, } @article {pmid37104426, year = {2023}, author = {Toresson, L and Spillmann, T and Pilla, R and Ludvigsson, U and Hellgren, J and Olmedal, G and Suchodolski, JS}, title = {Clinical Effects of Faecal Microbiota Transplantation as Adjunctive Therapy in Dogs with Chronic Enteropathies-A Retrospective Case Series of 41 Dogs.}, journal = {Veterinary sciences}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/vetsci10040271}, pmid = {37104426}, issn = {2306-7381}, abstract = {Chronic enteropathies (CE) are common in dogs, but not all affected dogs respond to standard therapy. Successful responses to faecal microbial transplantation (FMT) in dogs with non-responsive CE have been reported in two case series. The objective of this retrospective study was to describe the clinical effects of FMT as an adjunctive therapy in a larger population of dogs with CE. Forty-one dogs aged 0.6-13.0 years (median 5.8) under treatment for CE at one referral animal hospital were included. Dogs were treated with 1-5 (median 3) FMTs as a rectal enema at a dose of 5-7 g/kg body weight. The canine inflammatory bowel disease activity index (CIBDAI) was compared at baseline versus after the last FMT. Stored faecal samples (n = 16) were analysed with the dysbiosis index. CIBDAI at baseline was 2-17 (median 6), which decreased to 1-9 (median 2; p < 0.0001) after FMT. Subsequently, 31/41 dogs responded to treatment, resulting in improved faecal quality and/or activity level in 24/41 and 24/41 dogs, respectively. The dysbiosis index at baseline was significantly lower for good responders versus poor responders (p = 0.043). Results suggest that FMT can be useful as an adjunctive therapy in dogs with poorly responsive CE.}, } @article {pmid37104044, year = {2023}, author = {Cunningham, A and Harris, DA}, title = {Gut microbiota analysis and faecal transplantation to improve surgical outcomes.}, journal = {The British journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjs/znad102}, pmid = {37104044}, issn = {1365-2168}, } @article {pmid37102320, year = {2023}, author = {Tao, J and An, Y and Xu, L and Wang, Y and Wang, C and Li, P and Li, M and Yan, D and Wang, M and Zhong, G and Wu, M}, title = {The protective role of microbiota in the prevention of MPTP/P-induced Parkinson's disease by resveratrol.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2fo03379h}, pmid = {37102320}, issn = {2042-650X}, abstract = {Parkinson's disease (PD) is a tricky neurodegenerative disease characterized with motor deficits and gastrointestinal (GI) dysfunction. Gut microbiota disturbance is reported to be involved in the clinical phenotypes of PD and its pathogenesis through the brain-gut-microbiota axis. Resveratrol is a natural polyphenol that possesses various biological activities in alleviating many diseases, including PD. The present study was aimed to investigate the role of gut microbiota in resveratrol-treated PD mice. A chronic mouse model of PD was generated via the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/P) for 5 consecutive weeks. Resveratrol was orally administered once a day (30 mg kg[-1] d[-1]) for a total of 8 weeks. From the 6[th] week to the 8[th] week, fecal microbiota transplantation (FMT) was performed from resveratrol-treated PD mice to PD mice to evaluate the contribution of resveratrol-shaped microbiota in the alleviation of PD. The results showed that FMT from resveratrol-shaped microbiota remarkably alleviated the mice phenotype from PD progression, including increased latency in the rotarod, shortened beam walking time, increased the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and enriched TH-positive fiber density in the striatum. Further experiments revealed that FMT could ameliorate the GI dysfunction by increasing the small intestinal transport rate and the colon length, decreasing the relative abundances of inflammatory cytokines (TNF-α, IL-6 and IL-1β) in colon epithelial tissue. The 16S rDNA sequencing indicated that FMT attenuated the gut microbial dysbiosis in PD mice by increasing the abundances of Prevotellaceae, Rikenellaceae, Erysipelotrichaceae, Blautia and Alistipes, lowering the ratio of Fimicutes/Bacteroidetes, and decreasing the abundances of Lachnospiraceae and Akkermansia. Therefore, results in this study demonstrated that gut microbiota played a vital role in the prevention of PD progression, and the shaping of the gut microbiota was the pharmacological mechanism of resveratrol in alleviating the phenotype of Parkinson's disease in PD mice.}, } @article {pmid37101273, year = {2023}, author = {Tie, X and Zhang, Z and Zhou, R and Li, Y and Xu, J and Yin, W}, title = {A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {260}, pmid = {37101273}, issn = {1471-2334}, abstract = {BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage.

CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case.

CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100-300/mm[3] was highly effective against Cryptosporidium without inducing immunorejection.}, } @article {pmid37099039, year = {2023}, author = {Sun, J and Xu, G}, title = {Mesenchymal Stem Cell-Derived Exosomal miR-150-3p Affects Intracerebral Hemorrhage By Regulating TRAF6/NF-κB Axis, Gut Microbiota and Metabolism.}, journal = {Stem cell reviews and reports}, volume = {}, number = {}, pages = {}, pmid = {37099039}, issn = {2629-3277}, abstract = {Intracerebral hemorrhage (ICH) is a severe subtype of stroke for which there is no effective treatment. Stem cell and exosome (Exo) therapies have great potential as new approaches for neuroprotection and neurorestoration in treating ICH. We aimed to investigate whether Exo affects ICH by regulating the ecology of gut microbiota and metabolism and the mechanisms involved. First, differential miRNAs in ICH were screened by bioinformatics and verified by qRT-PCR. Then, Exo was extracted from mouse bone marrow mesenchymal stem cells (MSCs) and identified. Dual-luciferase reporter gene assay was utilized to verify the binding relationship between miR-150-3p and TRAF6. A mouse ICH model was constructed and treated with Exo. Next, we knocked down miR-150-3p and performed fecal microbiota transplantation (FMT). Then changes in gut microbiota and differential metabolites were detected by 16S rRNA sequencing and metabolomics analysis. We found that miR-150-3p expression was lowest in the brain tissue of the ICH group compared to the Sham group. Besides, low miR-150-3p level in ICH was encapsulated by MSC-derived Exo. Moreover, miR-150-3p bound to TRAF6 and was negatively correlated. With the addition of Exo[miR-150-3p inhibitor], we found that MSC-derived exosomal miR-150-3p may affect ICH injury via TRAF6/NLRP3 axis. MSC-derived exosomal miR-150-3p caused changes in gut microbiota, including Proteobacteria, Muribaculaceae, Lachnospiraceae_NK4A136_group, and Acinetobacter. Moreover, MSC-derived exosomal miR-150-3p caused changes in metabolism. After further FMT, gut microbiota-mediated MSC-derived Exo affected ICH with reduced apoptosis and reduced levels of inflammatory factors. In conclusion, MSC-derived exosomal miR-150-3p affected ICH by regulating TRAF6/NF-κB axis, gut microbiota and metabolism.}, } @article {pmid37098448, year = {2023}, author = {Porcari, S and Baunwall, SMD and Occhionero, AS and Ingrosso, MR and Ford, AC and Hvas, CL and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: A systematic review and meta-analysis.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103036}, doi = {10.1016/j.jaut.2023.103036}, pmid = {37098448}, issn = {1095-9157}, abstract = {Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.}, } @article {pmid37096495, year = {2023}, author = {Minkoff, NZ and Aslam, S and Medina, M and Tanner-Smith, EE and Zackular, JP and Acra, S and Nicholson, MR and Imdad, A}, title = {Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).}, journal = {The Cochrane database of systematic reviews}, volume = {4}, number = {4}, pages = {CD013871}, pmid = {37096495}, issn = {1469-493X}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Clostridioides ; Quality of Life ; Dysbiosis ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials.

OBJECTIVES: To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022.

SELECTION CRITERIA: We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome.

MAIN RESULTS: We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I[2] = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I[2] = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates.

AUTHORS' CONCLUSIONS: In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.}, } @article {pmid37095192, year = {2023}, author = {Zhou, X and Zhang, X and Niu, D and Zhang, S and Wang, H and Zhang, X and Nan, F and Jiang, S and Wang, B}, title = {Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6701}, pmid = {37095192}, issn = {2045-2322}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Fructose/metabolism ; Liver/metabolism ; Diet ; *Non-alcoholic Fatty Liver Disease/metabolism ; Inflammation/metabolism ; Diet, High-Fat ; Mice, Inbred C57BL ; }, abstract = {Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.}, } @article {pmid37094913, year = {2023}, author = {Rinninella, E and Tohumcu, E and Raoul, P and Fiorani, M and Cintoni, M and Mele, MC and Cammarota, G and Gasbarrini, A and Ianiro, G}, title = {The role of diet in shaping human gut microbiota.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {62-63}, number = {}, pages = {101828}, doi = {10.1016/j.bpg.2023.101828}, pmid = {37094913}, issn = {1532-1916}, abstract = {Gut microbiota plays a fundamental role within human health, and exerts key functions within the human body. Diet is one of the most powerful modulators of gut microbiota functions and composition. This complex interplay involves also the immune system and the intestinal barrier, highlighting the central role of diet in the pathogenesis and treatment of multiple diseases. In this review article we will paint the landscape of the effects of specific dietary nutrients, and of the detrimental or beneficial outcomes of different dietary patterns, on the composition of human gut microbiota. Moreover, we will discuss the potential application of diet as a therapeutic modulator of gut microbiota, including cutting-edge ways of exploitation, including the use of dietary components as adjuvants to promote microbial engraftment after fecal microbiota transplantation, or personalized nutritional approaches, targeted to the patient microbiome.}, } @article {pmid37094824, year = {2023}, author = {Imdad, A and Pandit, NG and Zaman, M and Minkoff, NZ and Tanner-Smith, EE and Gomez-Duarte, OG and Acra, S and Nicholson, MR}, title = {Fecal transplantation for treatment of inflammatory bowel disease.}, journal = {The Cochrane database of systematic reviews}, volume = {4}, number = {}, pages = {CD012774}, pmid = {37094824}, issn = {1469-493X}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT).

OBJECTIVES: To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022.

SELECTION CRITERIA: We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence.

MAIN RESULTS: We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD.

AUTHORS' CONCLUSIONS: FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.}, } @article {pmid37094397, year = {2023}, author = {Luo, H and Ying, N and Zhao, Q and Chen, J and Xu, H and Jiang, W and Wu, Y and Wu, Y and Gao, H and Zheng, H}, title = {A novel polysaccharide from Rubus chingii Hu unripe fruits: Extraction optimization, structural characterization and amelioration of colonic inflammation and oxidative stress.}, journal = {Food chemistry}, volume = {421}, number = {}, pages = {136152}, doi = {10.1016/j.foodchem.2023.136152}, pmid = {37094397}, issn = {1873-7072}, abstract = {Raspberry is used as a medicine food homology species and its polysaccharides are worthy being investigated and developed. In the present study, a novel polysaccharide of unripe raspberry fruits (pRCP) was extracted and characterized. The results show that pRCP was an acidic heteropolysaccharide and its Mw value was 74.86 kDa with a high homogeneity. The main chain of pRCP consisted of → 3,6)-β-Galp(1 → and → 5)-α-Araf(1→, and its side chain was composed of α-Araf(1 → linked to the C3 position of → 3,6)-β-Galp(1 →. In addition, pRCP supplementation increased the gut microbial diversity and reduced harmful bacteria including Erysipelatoclostridium and Negativibacillus in high-fat diet (HFD)-fed mice. Treatment with pRCP also alleviated HFD-induced colonic inflammation and oxidative stress in mice. These beneficial effects can be transferred to recipient mice by faecal microbiota transplantation from pRCP-treated mice. Therefore, our study suggests that pRCP could be used as a potential prebiotics to improve intestinal health by modulating the gut microbiota.}, } @article {pmid37093541, year = {2023}, author = {Anirvan, P and Panigrahi, MK and Singh, SP}, title = {Fecal microbiota transplantation in alcoholic hepatitis: new treatment paradigm or a shot in the dark?.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {37093541}, issn = {1936-0541}, } @article {pmid37093057, year = {2023}, author = {Chen, Q and Fan, Y and Zhang, B and Yan, C and Zhang, Q and Ke, Y and Chen, Z and Wang, L and Shi, H and Hu, Y and Huang, Q and Su, J and Xie, C and Zhang, X and Zhou, L and Ren, J and Xu, H}, title = {Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0415222}, doi = {10.1128/spectrum.04152-22}, pmid = {37093057}, issn = {2165-0497}, abstract = {Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.}, } @article {pmid37091531, year = {2023}, author = {Bachour, SP and Dalal, R and Allegretti, JR}, title = {The impact of the COVID-19 pandemic on Clostridioides difficile infection and utilization of fecal microbiota transplantation.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231165581}, pmid = {37091531}, issn = {1756-283X}, abstract = {Previous research has demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains cell entry through the angiotensin-converting enzyme 2 receptor, which is abundantly found throughout the gastrointestinal (GI) tract, resulting in a wide array of GI manifestations of coronavirus disease 2019 (COVID-19). By gaining entry into the intestinal epithelial and stromal cells, SARS-CoV-2 has been observed to cause intestinal inflammation and gut dysbiosis. Alterations in gut microbiota are known to be involved in the pathophysiology of Clostridioides difficile infection (CDI). During the initial stages of the COVID-19 pandemic, rates of CDI were similar to historical data despite the increased use of antibiotics. This may be due to increased emphasis on hygiene and protective equipment and reduced C. difficile testing as diarrhea was presumed to be COVID-19 related. Studies also demonstrated additional risk factors for CDI in COVID-19 patients, including length of hospitalization and new abdominal pain during admission. Although not associated with increased mortality, CDI was associated with increased length of hospital stay among patients admitted with COVID-19. Due to fecal viral shedding and concern of oral-fecal transmission of SARS-CoV-2, increased safety regulations were introduced to fecal microbiota transplantation (FMT) leading to reduced rates of this procedure during the COVID-19 pandemic. FMT for recurrent CDI during the COVID-19 pandemic remained highly effective without any reports of SARS-CoV-2 transmission. In addition, limited data show that FMT may be effective in treating COVID-19 and restoring healthy gut microbiota. The goal of this article is to review the impact that the COVID-19 pandemic has had on hospital-acquired CDI and the utilization of FMT.}, } @article {pmid37089571, year = {2023}, author = {Zhang, M and Sasaki, H and Yang, T and Chen, J and Li, R and Yi, C and Li, J and He, M and Yi, SQ}, title = {Fecal microbiota transplantation from Suncus murinus, an obesity-resistant animal, to C57BL/6NCrSIc mice, and the antibiotic effects in the approach.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1138983}, pmid = {37089571}, issn = {1664-302X}, abstract = {INTRODUCTION: Important studies on the relationship of the intestinal microbial flora with obesity have uncovered profound changes in the composition of the gut microbiota in obese individuals. Animal studies successfully altered body phenotypes by fecal microbiota transplantation (FMT).

METHODS: In this study, we analyzed the gut microbiome of Suncus murinus (S. murinus), a naturally obesity-resistant animal, and the changes of the gut flora of C57BL/6NCrSIc mice that received gut bacteria transplantation from S. murinus by 16S rRNA gene analysis method. And analyzed and discussed the possible impact of the use of antibiotics before transplantation on the outcome of transplantation.

RESULTS: Our results showed no significant changes in body weight in the FMT group compared to the control (AB) group, but large fluctuations due to antibiotics. There was no change in blood lipid levels between groups before and after FMT. The gut microbiota of S. murinus were enriched in Firmicutes and Proteobacteria, while Bacteroidetes were not detected, and fewer OTUs were detected in the intestine gut in comparison to other mouse groups. Statistically significant differences in alpha diversity were observed between the FMT group and other groups. Furthermore, a beta diversity analysis indicated an apparent structural separation between the FMT group and other groups.

CONCLUSION: It was suggested that the gut flora of S. murinus was not well established in the gut trace of mice through FMT, and the administration of antibiotics before transplantation was an important factor affecting the overall composition of the gut flora. Although FMT of S. murinus failed to completely colonize the intestinal tract of the mice, it still had a certain effect on the establishment of the intestinal flora of the mice. The unpredictable effects of pre-transplantation antibiotics on the results of transplantation cannot be ignored.}, } @article {pmid37089558, year = {2023}, author = {Li, JH and Liu, JL and Li, XW and Liu, Y and Yang, JZ and Chen, LJ and Zhang, KK and Xie, XL and Wang, Q}, title = {Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1143648}, pmid = {37089558}, issn = {1664-302X}, abstract = {INTRODUCTION: Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression.

METHODS: Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq.

RESULTS: We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway.

DISCUSSION: In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.}, } @article {pmid37089545, year = {2023}, author = {Montero, I and Barrientos, D and Hidalgo-Cantabrana, C and Martínez-Álvarez, N}, title = {GutAlive[®] enables DNA-based microbiome analysis without disrupting the original composition and diversity.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1118291}, pmid = {37089545}, issn = {1664-302X}, abstract = {INTRODUCTION: A precise fecal microbiome analysis requires normalized methods for microbiome sampling, transport and manipulation in order to obtain a representative snapshot of the microbial community. GutAlive[®] is the unique stool collection kit that generates an anaerobic atmosphere enabling oxygen sensitive bacteria to survive, maintaining the original microbiome composition and diversity.

METHODS: Five stool samples from different donors were collected using two different sampling devices, GutAlive[®] and Zymo DNA/RNA Shield[®], and processed at four different time points. Shotgun metagenomics was used to evaluate the influence of the device and the processing timing on the microbial populations to unravel the potential fluctuations on the composition and diversity of the fecal microbiome and the metabolic pathways profiling. Additionally, RT-qPCR was used to quantify bacterial cell viability for downstream applications of microbiota samples beyond metagenomics.

RESULTS: Our results show that GutAlive[®] enables bacterial cell viability overtime preserving DNA integrity, obtaining high-quantity and high-quality DNA to perform microbiome analysis using shotgun metagenomics. Based on the taxonomic profiling, metabolic pathways analysis, phylogeny and metagenome-assembled genomes, GutAlive[®] displayed greater performance without significant variability over time, showcasing the stabilization of the microbiome preserving the original composition and diversity. Indeed, this DNA stabilization is enabled with the preservation of bacterial viability on an anaerobic environment inside of the sampling device, without the addition of any reagents that interact directly with sample.

CONCLUSION: All the above makes GutAlive[®] an user-friendly kit for self-collection of biological samples, suitable for microbiome analysis, diagnostics, fecal microbiota transplant and bacterial isolation, maintaining the stability and bacterial viability over time, preserving the original composition and diversity of the microbiome.}, } @article {pmid37087457, year = {2023}, author = {Gu, F and Zhu, S and Hou, J and Tang, Y and Liu, JX and Xu, Q and Sun, HZ}, title = {The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {87}, pmid = {37087457}, issn = {2049-2618}, abstract = {BACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice.

RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota.

CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.}, } @article {pmid37087392, year = {2023}, author = {Mullish, BH and Tohumcu, E and Porcari, S and Fiorani, M and Di Tommaso, N and Gasbarrini, A and Cammarota, G and Ponziani, FR and Ianiro, G}, title = {The role of faecal microbiota transplantation in chronic noncommunicable disorders.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103034}, doi = {10.1016/j.jaut.2023.103034}, pmid = {37087392}, issn = {1095-9157}, abstract = {The gut microbiome plays a key role in influencing several pathways and functions involved in human health, including metabolism, protection against infection, and immune regulation. Perturbation of the gut microbiome is recognised as a pathogenic factor in several gastrointestinal and extraintestinal disorders, and is increasingly considered as a therapeutic target in these conditions. Faecal microbiota transplantation (FMT) is the transfer of the microbiota from healthy screened stool donors into the gut of affected patients, and is a well-established and highly effective treatment for recurrent Clostridioides difficile infection. Despite the mechanisms of efficacy of FMT not being fully understood, it has been investigated in several chronic noncommunicable disorders, with variable results. This review aims to give an overview of mechanisms of efficacy of FMT in chronic noncommunicable disorders, and to paint the current landscape of its investigation in these medical conditions, including inflammatory bowel disease (IBD), chronic liver disorders, and also extraintestinal autoimmune conditions.}, } @article {pmid37087075, year = {2023}, author = {Zhu, M and Ouyang, J and Zhou, F and Zhao, C and Zhu, W and Liu, C and Huang, P and Li, J and Tang, J and Zhang, Z and Huang, J and Wu, M and Wang, K and Liu, Z}, title = {Polysaccharides from Fu brick tea ameliorate obesity by modulating gut microbiota and gut microbiota-related short chain fatty acid and amino acid metabolism.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109356}, doi = {10.1016/j.jnutbio.2023.109356}, pmid = {37087075}, issn = {1873-4847}, abstract = {Fu brick tea (FBT) is a traditional tea manufactured by solid-state fermentation of tea leaves (Camellia sinensis). Although anti-obesity effects have been reported for FBT, the associated role of FBT polysaccharides (PSs) and the underlying mechanisms remain unknown. In this study, we found that FBTPSs inhibited obesity, hyperlipidemia, and inflammation; improved intestinal barrier function; and alleviated gut microbiota dysbiosis in high-fat diet-fed rats. Akkermansia muciniphila, Bacteroides, Parasutterella, Desulfovibrio, and Blautia were the core microbes regulated by FBTPSs. FBTPSs regulated the production of gut microbiota-related metabolites, including short-chain fatty acids (SCFAs), branched-chain amino acids, and aromatic amino acids throughout the development of obesity, and regulated the SCFA-GPR signaling pathway. FBTPS-treated fecal microbiota transplant ameliorated obesity, alleviated gut microbiota dysbiosis, and improved gut microbiota-associated metabolites, suggesting that the anti-obesity effect of FBTPSs was gut microbiota-dependent. FBTPSs may serve as novel prebiotic agents for the treatment of obesity and dysbiosis of gut microbiota.}, } @article {pmid37085966, year = {2023}, author = {Zhong, P and Wu, H and Ma, Y and Xu, X and Jiang, Y and Jin, C and Zhu, Q and Liu, X and Suo, Z and Wang, J}, title = {P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis.}, journal = {Clinical and translational medicine}, volume = {13}, number = {4}, pages = {e1227}, doi = {10.1002/ctm2.1227}, pmid = {37085966}, issn = {2001-1326}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms.

METHODS: Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild-type mice. Clinical and histopathological parameters were monitored throughout the disease progression.

RESULTS: Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS-induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor-positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild-type C57BL/6 mice. Further antibiotic-treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4.

CONCLUSIONS: Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.}, } @article {pmid37085337, year = {2023}, author = {Porcari, S and Severino, A and Rondinella, D and Bibbò, S and Quaranta, G and Masucci, L and Maida, M and Scaldaferri, F and Sanguinetti, M and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103033}, doi = {10.1016/j.jaut.2023.103033}, pmid = {37085337}, issn = {1095-9157}, abstract = {AIMS: Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection.

METHODS AND RESULTS: In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed.

CONCLUSIONS: In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.}, } @article {pmid37085058, year = {2023}, author = {Chen, C and Liu, L and Zhong, Y and Wang, M and Ai, Y and Hou, Y and Chen, H and Lin, X and Zhang, Y and Ding, M and Luo, T and Li, J and Li, X and Xiao, X}, title = {Gut microbiota-bile acids-glucagon like peptide-1 axis contributes the resistance to high fat diet-induced obesity in mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109358}, doi = {10.1016/j.jnutbio.2023.109358}, pmid = {37085058}, issn = {1873-4847}, abstract = {In human and rodents, some individuals may remain lean even when they are challenged with high calorie intake. The underlying mechanism for resistance to diet-induced obesity was poorly understood. Here, we used C57BL/6J mice to establish animal models of high-fat diet (HFD) induced obesity sensitive (DIO) mice and obesity resistant (DIR) mice. We then investigated the role of gut microbiota, bile acids (BAs) and brown adipose tissue (BAT) thermogenesis in the development of DIR. Reduced fat accumulation, increased glucose tolerance and energy expenditure through BAT activation were observed in DIR mice. The plasma BAs of DIR mice especially the unconjugated BAs were significantly decreased, while intestine tauro-conjugated bile acids (T-CA, T-β-MCA, T-ω-MCA and T-UDCA) were significantly increased in DIR mice. The composition of the gut flora also changed drastically, and negative correlation was found between metabolic profiles (plasma TG, TC, LDL and body weight) and the abundance of Ruminiclostridium in DIR mice, while genus Anaerotruncus abundance in DOR mice was found to be positively correlated. After fecal microbiota transplants, HFD fed recipient mice exhibited a trend toward reduced adiposity and improved glucose tolerance, while showing increased serum tauro-conjugated BAs levels. STC-1 cell experiments confirmed tauro-conjugated BA (T-β-MCA) activated FXR/TGR5 pathway and induced the production of GLP-1, inhibiting genes that regulate the ceramide synthesis. Our results indicated that the DIR mice exhibited higher energy expenditure by activating BAT thermogenesis, which may be related altered gut microbiota-bile acids-glucagon like peptide-1 axis.}, } @article {pmid37083877, year = {2023}, author = {Lei, Y and Liu, Q and Li, Q and Zhao, C and Zhao, M and Lu, Q}, title = {Exploring the Complex Relationship Between Microbiota and Systemic Lupus Erythematosus.}, journal = {Current rheumatology reports}, volume = {}, number = {}, pages = {}, pmid = {37083877}, issn = {1534-6307}, abstract = {PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various autoantibodies and multi-organ. Microbiota dysbiosis in the gut, skin, oral, and other surfaces has a significant impact on SLE development. This article summarizes relevant research and provides new microbiome-related strategies for exploring the mechanisms and treating patients with SLE.

RECENT FINDINGS: SLE patients have disruptions in multiple microbiomes, with the gut microbiota (bacteria, viruses, and fungi) and their metabolites being the most thoroughly researched. This dysbiosis can promote SLE progression through mechanisms such as the leaky gut, molecular mimicry, and epigenetic regulation. Notwithstanding study constraints on the relationship between microbiota and SLE, specific interventions targeting the gut microbiota, such as probiotics, dietary management, and fecal microbiota transplantation, have emerged as promising SLE therapeutics.}, } @article {pmid37083032, year = {2023}, author = {Chancharoenthana, W and Kamolratanakul, S and Schultz, MJ and Leelahavanichkul, A}, title = {The leaky gut and the gut microbiome in sepsis - targets in research and treatment.}, journal = {Clinical science (London, England : 1979)}, volume = {137}, number = {8}, pages = {645-662}, doi = {10.1042/CS20220777}, pmid = {37083032}, issn = {1470-8736}, abstract = {Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1→3)-β-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.}, } @article {pmid37081964, year = {2023}, author = {Bao, K and Wang, M and Liu, L and Zhang, D and Jin, C and Zhang, J and Shi, L}, title = {Jinhong decoction protects sepsis-associated acute lung injury by reducing intestinal bacterial translocation and improving gut microbial homeostasis.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1079482}, pmid = {37081964}, issn = {1663-9812}, abstract = {Background: Currently no specific treatments are available for sepsis and the associated syndromes including acute lung injury (ALI). Jinhong Decoction (JHD) is a traditional Chinese prescription, and it has been applied clinically as an efficient and safe treatment for sepsis, but the underlying mechanism remains unknown. The aim of the study was to explore the potential mechanisms of JHD ameliorating sepsis and concurrent ALI. Methods: The cecum ligation puncture (CLP)- induced murine sepsis model was established for determining the efficacy of JHD protecting CLP and ALI. The role of gut microbiota involved in the efficacy of JHD was evaluated by 16S rRNA sequencing and fecal microbiota transplantation (FMT). Translocation of intestinal Escherichia coli (E. coli) to lungs after CLP was verified by qPCR and in vivo-imaging. Intestinal permeability was analyzed by detecting FITC-dextran leakness. Junction proteins were evaluated by Western blotting and immunofluorescence. Results: JHD treatment remarkably increased survival rate of septic mice and alleviated sepsis-associated lung inflammation and injury. FMT suggested that the protective role for JHD was mediated through the regulation of gut microbiota. We further revealed that JHD administration partially restored the diversity and configuration of microbiome that was distorted by CLP operation. Of interest, the intestinal bacteria, E. coli particularly, was found to translocate into the lungs upon CLP via disrupting the intestinal mucosal barrier, leading to the inflammatory response and tissue damage in lungs. JHD impeded the migration and hence lung accumulation of intestinal E. coli, and thereby prevented severe ALI associated with sepsis. This effect is causatively related with the ability of JHD to restore intestinal barrier by up-regulating tight junctions. Conclusion: Our study unveils a mechanism whereby the migration of gut bacteria leads to sepsis-associated ALI, and we demonstrate the potential of JHD as an effective strategy to block this bacterial migration for treating sepsis and the associated immunopathology in the distal organs.}, } @article {pmid37078497, year = {2023}, author = {Zhou, B and Pang, X and Wu, J and Liu, T and Wang, B and Cao, H}, title = {Gut microbiota in COVID-19: new insights from inside.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2201157}, doi = {10.1080/19490976.2023.2201157}, pmid = {37078497}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like Bifidobacterium and Faecalibacterium and enrichment of inflammation-associated microbiota including Streptococcus and Actinomyces. Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.}, } @article {pmid37077050, year = {2023}, author = {Wu, LQ and Yuan, QF and Qin, ZC and Xu, YD and Li, L and Xu, JT and He, XX and Xie, WR and Wu, LH}, title = {Faecal microbiota transplantation for treatment of chronic urticaria with recurrent abdominal pain and food allergy.}, journal = {Singapore medical journal}, volume = {}, number = {}, pages = {}, doi = {10.4103/singaporemedj.SMJ-2021-423}, pmid = {37077050}, issn = {2737-5935}, } @article {pmid37076953, year = {2023}, author = {Li, J and Zhang, F and Zhao, L and Dong, C}, title = {Microbiota-gut-brain axis and related therapeutics in Alzheimer's disease: prospects for multitherapy and inflammation control.}, journal = {Reviews in the neurosciences}, volume = {}, number = {}, pages = {}, pmid = {37076953}, issn = {2191-0200}, abstract = {Alzheimer's disease (AD) is the most common type of dementia in the elderly and causes neurodegeneration, leading to memory loss, behavioral disorder, and psychiatric impairment. One potential mechanism contributing to the pathogenesis of AD may be the imbalance in gut microbiota, local and systemic inflammation, and dysregulation of the microbiota-gut-brain axis (MGBA). Most of the AD drugs approved for clinical use today are symptomatic treatments that do not improve AD pathologic changes. As a result, researchers are exploring novel therapeutic modalities. Treatments involving the MGBA include antibiotics, probiotics, transplantation of fecal microbiota, botanical products, and others. However, single-treatment modalities are not as effective as expected, and a combination therapy is gaining momentum. The purpose of this review is to summarize recent advances in MGBA-related pathological mechanisms and treatment modalities in AD and to propose a new concept of combination therapy. "MGBA-based multitherapy" is an emerging view of treatment in which classic symptomatic treatments and MGBA-based therapeutic modalities are used in combination. Donepezil and memantine are two commonly used drugs in AD treatment. On the basis of the single/combined use of these two drugs, two/more additional drugs and treatment modalities that target the MGBA are chosen based on the characteristics of the patient's condition as an adjuvant treatment, as well as the maintenance of good lifestyle habits. "MGBA-based multitherapy" offers new insights for the treatment of cognitive impairment in AD patients and is expected to show good therapeutic results.}, } @article {pmid37075927, year = {2023}, author = {Rakotonirina, A and Galperine, T and Audry, M and Kroemer, M and Baliff, A and Carrez, L and Sadeghipour, F and Schrenzel, J and Guery, B and Allémann, É}, title = {Dry alginate beads for fecal microbiota transplantation: from model strains to fecal samples.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {122961}, doi = {10.1016/j.ijpharm.2023.122961}, pmid = {37075927}, issn = {1873-3476}, abstract = {Clostridioides difficile infection (CDI) is a critical nosocomial infection with more than 124,000 cases per year in Europe and a mortality rate of 15-17%. The standard of care (SoC) is antibiotic treatment. Unfortunately, the relapse rate is high (∼35%) and SoC is significantly less effective against recurrent infection (rCDI). Fecal microbiota transplantation (FMT) is a recommended treatment against rCDI from the second recurrence episode and has an efficacy of 90%. The formulation of diluted donor stool deserves innovation because its actual administration routes deserve optimization (naso-duodenal/jejunal tubes, colonoscopy, enema or several voluminous oral capsules). Encapsulation of model bacteria strains in gel beads were first investigated. Then, the encapsulation method was applied to diluted stools. Robust spherical gel beads were obtained. The mean particle size was around 2 mm. A high loading of viable microorganisms was obtained for model strains and fecal samples. For plate-counting, values ranged from 10[15] to 10[17] CFU/g for single and mixed model strains, and 10[6] to 10[8] CFU/g for fecal samples. This corresponded to a viability of 30% to 60% as assessed by flow cytometry. This novel formulation is promising as the technology is applicable to both model strains and bacteria contained in the gut microbiota.}, } @article {pmid37074200, year = {2023}, author = {Chen, Q and Ma, X and Xing, Z and Zhao, X and Zu, H and Guo, Z and Li, B}, title = {Antibiotic Conditioning Shapes Pseudosterile Mouse Models by Deleting Colonic Microbes Rather than Small Intestinal Microbes.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0081423}, doi = {10.1128/spectrum.00814-23}, pmid = {37074200}, issn = {2165-0497}, abstract = {A simple model of alternative microbiota in the developing intestinal environment has been highly desirable for the study of health and disease in the gut. The pattern of antibiotic depletion of natural gut microbes is necessary for this model. However, the effects and loci of antibiotic deletion of gut microbes remain unclear. In this study, a mixture of three proven broad-spectrum antibiotics was selected to study their effects on microbial deletions in the jejunum, ileum, and colon of mice. The 16S rRNA sequencing results showed that antibiotics significantly reduced colonic microbial diversity, with limited effects on the jejunum and ileum. At the level of microbial genera, only 93.38% of Burkholderia-Caballeronia-Paraburkholderia and 5.89% of Enterorhabdus were present in the colon after antibiotic treatment. However, such changes were not observed in the microbial composition of the jejunum and ileum. Our results suggest that the antibiotics depleted intestinal microorganisms by acting primarily in the colon and not in the small intestine (jejunum and ileum). IMPORTANCE Many studies have applied antibiotics to delete intestinal microbes to shape pseudosterile mouse models and further used for fecal microbial transplantation. However, few studies have explored the spatial location of antibiotic action in the intestine. This study shows that the selected antibiotics effectively deleted microbiota in the colon of mice, with limited effects on microbes in the jejunum and ileum. Our study provides guidance for the application of a mouse model of antibiotic deletion of intestinal microbes.}, } @article {pmid37069691, year = {2023}, author = {Zhao, C and Hu, X and Qiu, M and Bao, L and Wu, K and Meng, X and Zhao, Y and Feng, L and Duan, S and He, Y and Zhang, N and Fu, Y}, title = {Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {78}, pmid = {37069691}, issn = {2049-2618}, mesh = {Humans ; Female ; Animals ; Cattle ; Mice ; *Gastrointestinal Microbiome/physiology ; N-Acetylneuraminic Acid ; Dysbiosis/chemically induced ; *Mastitis ; *Microbiota ; Enterobacteriaceae ; Escherichia coli ; }, abstract = {BACKGROUND: Mastitis is one of the most severe diseases in humans and animals, especially on dairy farms. Mounting evidence indicates that gastrointestinal dysbiosis caused by induction of subacute ruminal acidosis (SARA) by high-grain diet consumption and low in dietary fiber is associated with mastitis initiation and development, however, the underlying mechanism remains unknown.

RESULTS: In the present study, we found that cows with SARA-associated mastitis have altered metabolic profiles in the rumen, with increased sialic acids level in particular. Consumption of sialic acid (SA) in antibiotic-treated mice, but not healthy mice, induced marked mastitis. SA treatment of antibiotic-treated mice also induced mucosal and systemic inflammatory responses, as evidenced by increased colon and liver injuries and several inflammatory markers. In addition, gut dysbiosis caused by antibiotic impaired gut barrier integrity, which was aggravated by SA treatment. SA potentiated serum LPS level caused by antibiotic treatment, leading to increased activation of the TLR4-NF-κB/NLRP3 pathways in the mammary gland and colon. Moreover, SA facilitated gut dysbiosis caused by antibiotic, and especially enhanced Enterobacteriaceae and Akkermansiaceae, which correlated with mastitis parameters. Fecal microbiota transplantation from SA-antibiotic-treated mice mimicked mastitis in recipient mice. In vitro experiments showed that SA prompted Escherichia coli growth and virulence gene expression, leading to higher proinflammatory cytokine production in macrophages. Targeting the inhibition of Enterobacteriaceae by sodium tungstate or treating with the commensal Lactobacillus reuteri alleviated SA-facilitated mastitis. In addition, SARA cows had distinct ruminal microbial structure by the enrichment of SA-utilizing opportunistic pathogenic Moraxellaceae and the depletion of SA-utilizing commensal Prevotellaceae. Treating mice with the specific sialidase inhibitor zanamivir reduced SA production and Moraxellaceae abundance, and improved mastitis in mice caused by ruminal microbiota transplantation from cows with SARA-associated mastitis.

CONCLUSIONS: This study, for the first time, indicates that SA aggravates gut dysbiosis-induced mastitis by promoting gut microbiota disturbance and is regulated by commensal bacteria, indicating the important role of the microbiota-gut-mammary axis in mastitis pathogenesis and suggesting a potential strategy for mastitis intervention based on gut metabolism regulation. Video Abstract.}, } @article {pmid36847237, year = {2023}, author = {}, title = {Fecal microbiota, live-jslm.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {80}, number = {9}, pages = {e79-e80}, doi = {10.1093/ajhp/zxad032}, pmid = {36847237}, issn = {1535-2900}, mesh = {Humans ; Feces ; *Fecal Microbiota Transplantation ; *Microbiota ; }, } @article {pmid37069665, year = {2023}, author = {Watson, AR and Füssel, J and Veseli, I and DeLongchamp, JZ and Silva, M and Trigodet, F and Lolans, K and Shaiber, A and Fogarty, E and Runde, JM and Quince, C and Yu, MK and Söylev, A and Morrison, HG and Lee, STM and Kao, D and Rubin, DT and Jabri, B and Louie, T and Eren, AM}, title = {Metabolic independence drives gut microbial colonization and resilience in health and disease.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {78}, pmid = {37069665}, issn = {1474-760X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Microbiota ; Metagenomics ; Amino Acids ; Feces ; }, abstract = {BACKGROUND: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.

RESULTS: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.

CONCLUSIONS: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.}, } @article {pmid37069399, year = {2023}, author = {Fan, Y and Støving, RK and Berreira Ibraim, S and Hyötyläinen, T and Thirion, F and Arora, T and Lyu, L and Stankevic, E and Hansen, TH and Déchelotte, P and Sinioja, T and Ragnarsdottir, O and Pons, N and Galleron, N and Quinquis, B and Levenez, F and Roume, H and Falony, G and Vieira-Silva, S and Raes, J and Clausen, L and Telléus, GK and Bäckhed, F and Oresic, M and Ehrlich, SD and Pedersen, O}, title = {The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {37069399}, issn = {2058-5276}, abstract = {Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.}, } @article {pmid37067507, year = {2023}, author = {Wang, HR and Wang, MY and Sang, LX}, title = {How to Choose a Treatment for Immune Checkpoint Inhibitor-associated Colitis: Biologics, or Fecal Microbial Transplantation.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izad071}, pmid = {37067507}, issn = {1536-4844}, } @article {pmid37068743, year = {2022}, author = {Sheykhsaran, E and Abbasi, A and Ebrahimzadeh Leylabadlo, H and Sadeghi, J and Mehri, S and Naeimi Mazraeh, F and Feizi, H and Bannazadeh Baghi, H}, title = {Gut microbiota and obesity: an overview of microbiota to microbial-based therapies.}, journal = {Postgraduate medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1136/postmj/postgradmedj-2021-141311}, pmid = {37068743}, issn = {1469-0756}, abstract = {The increasing prevalence of obesity and overweight is a significant public concern throughout the world. Obesity is a complex disorder involving an excessive amount of body fat. It is not just a cosmetic concern. It is a medical challenge that increases the risk of other diseases and health circumstances, such as diabetes, heart disease, high blood pressure and certain cancers. Environmental and genetic factors are involved in obesity as a significant metabolic disorder along with diabetes. Gut microbiota (GM) has a high potential for energy harvesting from the diet. In the current review, we aim to consider the role of GM, gut dysbiosis and significant therapies to treat obesity. Dietary modifications, probiotics, prebiotics, synbiotics compounds, using faecal microbiota transplant, and other microbial-based therapies are the strategies to intervene in obesity reducing improvement. Each of these factors serves through various mechanisms including a variety of receptors and compounds to control body weight. Trial and animal investigations have indicated that GM can affect both sides of the energy-balancing equation; first, as an influencing factor for energy utilisation from the diet and also as an influencing factor that regulates the host genes and energy storage and expenditure. All the investigated articles declare the clear and inevitable role of GM in obesity. Overall, obesity and obesity-relevant metabolic disorders are characterised by specific modifications in the human microbiota's composition and functions. The emerging therapeutic methods display positive and promising effects; however, further research must be done to update and complete existing knowledge.}, } @article {pmid37067423, year = {2023}, author = {Wang, D and Zheng, Y and Fan, Y and He, Y and Liu, K and Deng, S and Liu, Y}, title = {Sodium Humate-Derived Gut Microbiota Ameliorates Intestinal Dysfunction Induced by Salmonella Typhimurium in Mice.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0534822}, doi = {10.1128/spectrum.05348-22}, pmid = {37067423}, issn = {2165-0497}, abstract = {Salmonella is a foodborne pathogen that is one of the main causes of gastroenteric disease in humans and animals. As a natural organic substance, sodium humate (HNa) possesses antibacterial, antidiarrheal, and anti-inflammatory properties. However, it is unclear whether the HNa and HNa-derived microbiota exert alleviative effects on Salmonella enterica serovar Typhimurium-induced enteritis. We found that treatment with HNa disrupted the cell wall of S. Typhimurium and decreased the virulence gene expression. Next, we explored the effect of HNa presupplementation on S. Typhimurium-induced murine enteritis. The results revealed that HNa ameliorated intestinal pathological damage. In addition, we observed that presupplementation with HNa enhanced intestinal barrier function via modulating gut microbiota, downregulating toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) signaling pathways, regulating intestinal mucosal immunity, and enhancing tight junction protein expression. To further validate the effect of HNa-derived microbiota on S. Typhimurium-induced enteritis, we performed fecal microbiota transplantation and found that HNa-derived microbiota also alleviated S. Typhimurium-induced intestinal damage. It is noteworthy that both HNa and HNa-derived microbiota improved the liver injury caused by S. Typhimurium infection. Collectively, this is the first study to confirm that HNa could alleviate S. Typhimurium-induced enteritis in a gut microbiota-dependent manner. This study provides a new perspective on HNa as a potential drug to prevent and treat salmonellosis. IMPORTANCE Salmonella Typhimurium is an important zoonotic pathogen, widely distributed in nature. S. Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from Salmonella infection each year, which poses a substantial risk to public health and causes a considerable economic loss. Here, we found that the S. Typhimurium infection caused severe intestinal and liver damage. In addition, we first found that sodium humate (HNa) and HNa-derived gut microbiota can alleviate S. Typhimurium infection-induced intestinal damage. These findings extend the knowledge about the public health risk and pathogenic mechanisms of S. Typhimurium.}, } @article {pmid37062804, year = {2023}, author = {Baek, OD and Hjermitslev, CK and Dyreborg, L and Baunwall, SMD and Høyer, KL and Rågård, N and Hammeken, LH and Povlsen, JV and Ehlers, LH and Hvas, CL}, title = {Early Economic Assessment of Faecal Microbiota Transplantation for Patients with Urinary Tract Infections Caused by Multidrug-Resistant Organisms.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {37062804}, issn = {2193-8229}, abstract = {INTRODUCTION: The use of faecal microbiota transplantation (FMT) to eradicate intestinal carriage of multidrug-resistant organisms (MDRO) has been described in case reports and small case series. Although few in numbers, these patients suffer from recurrent infections that may exacerbate both the patients' comorbidities and their healths. In the current study, we hypothesized that FMT for MDRO-related urinary tract infections (UTIs) reduces hospitalisations and associated costs.

METHODS: In a cohort of patients referred for FMT from 2015 to 2020, we selected all patients who had consecutively been referred for eradication of MRDO carriage with UTIs. An early economic assessment was performed to calculate hospital-related costs. The overall study cohort was registered at ClinicalTrials, study identifier NCT03712722.

RESULTS: We consecutively included five patients with UTIs caused by MDROs. Four of the patients were renal transplant recipients. Patients were followed for median 126 days (range 60-320), where the follow-up duration for each patient was aligned with the number of days from the first UTI to FMT. The median number of UTIs per patient dropped from 4 to 0. Investigating hospital costs, hospital admission days dropped by 87% and monthly hospital costs by 79%.

CONCLUSIONS: FMT was effective in reducing the occurrence of UTIs and mediated a marked reduction in hospital costs. We suggest that this strategy is cost-effective.

TRIAL REGISTRATION: ClinicalTrials, study identifier NCT03712722.}, } @article {pmid37062174, year = {2023}, author = {Benech, N and Sokol, H}, title = {Targeting the gut microbiota in inflammatory bowel diseases: where are we?.}, journal = {Current opinion in microbiology}, volume = {74}, number = {}, pages = {102319}, doi = {10.1016/j.mib.2023.102319}, pmid = {37062174}, issn = {1879-0364}, abstract = {The gut microbiota is now recognized to be a key driver of mucosal inflammation in inflammatory bowel disease (IBD). Robust functional and compositional alterations of the gut microbiota have been described in IBD with a reduction in bacterial diversity, a reduction in some anti-inflammatory anaerobic bacteria, and an increase in bacteria with pro-inflammatory potential. However, despite 15 years of active research, therapeutical applications are still lacking. Recent studies have shed new light on how targeting the gut microbiota can be beneficial in IBD with fecal microbiota transplantation, next-generation probiotics, and phage therapy. Given the similarities in dysfunction and structure of the gut microbiota between IBD and other chronic conditions associated with intestinal inflammation, such as celiac disease, Familial Mediterranean Fever, or common variable immunodeficiency, common therapeutic strategies targeting the host-microbiota symbiosis may be applied in these different conditions.}, } @article {pmid37059245, year = {2023}, author = {Gu, YY and Cui, XB and Jiang, J and Zhang, YX and Liu, MH and Cheng, SB and Li, YY and Liu, LL and Liao, RX and Zhao, P and Jin, W and Jia, YH and Wang, J and Zhou, FH}, title = {Dingxin recipe Ⅲ ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116483}, doi = {10.1016/j.jep.2023.116483}, pmid = {37059245}, issn = {1872-7573}, abstract = {Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date.

AIM OF THE STUDY: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia.

MATERIALS AND METHODS: The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions.

RESULTS: DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1.

CONCLUSION: DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.}, } @article {pmid37055440, year = {2023}, author = {Song, W and Sheng, Q and Bai, Y and Li, L and Ning, X and Liu, Y and Song, C and Wang, T and Dong, X and Luo, Y and Hu, J and Zhu, L and Cui, X and Chen, B and Li, L and Cai, C and Cui, H and Yue, T}, title = {Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4[+]CD25[+]Foxp3[+] Tregs-mediated gut microbiome of non-obese mice.}, journal = {NPJ science of food}, volume = {7}, number = {1}, pages = {14}, pmid = {37055440}, issn = {2396-8370}, abstract = {Osteoporosis is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. High-fat diet (HFD)-induced obesity also results in bone loss, which is associated with an imbalanced gut microbiome. However, whether HFD-induced obesity or HFD itself promotes osteoclastogenesis and consequent bone loss remains unclear. In this study, we developed HFD-induced obesity (HIO) and non-obesity (NO) mouse models to evaluate the effect of HFD on bone loss. NO mice were defined as body weight within 5% of higher or lower than that of chow diet fed mice after 10 weeks HFD feeding. NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number. This led to increased bone strength and improved bone microstructure via the microbiome-short-chain fatty acids (SCFAs) regulation. Additionally, endogenous gut-SCFAs produced by the NO mice activated free fatty acid receptor 2 and inhibited histone deacetylases, resulting in the promotion of Treg cell proliferation in the HFD-fed NO mice; thereby, inhibiting osteoclastogenesis, which can be transplanted by fecal microbiome. Furthermore, T cells from NO mice retain differentiation of osteoclast precursors of RAW 264.7 macrophages ex vivo. Our data reveal that HFD is not a deleterious diet; however, the induction of obesity serves as a key trigger of bone loss that can be blocked by a NO mouse-specific gut microbiome.}, } @article {pmid37052201, year = {2023}, author = {Jansen, D and Falony, G and Vieira-Silva, S and Simsek, C and Marcelis, T and Caenepeel, C and Machiels, K and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Community Types Of The Human Gut Virome Are Associated With Endoscopic Outcome In Ulcerative Colitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjad061}, pmid = {37052201}, issn = {1876-4479}, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD) is a major debilitating disease. Recently, the gut microbiota has gained attention as an important factor involved in the pathophysiology of IBD. As a complement to the established bacterial 'enterotypes' associated with IBD, we focussed on viruses. We investigated the intestinal virome of IBD patients undergoing biological therapy for the presence of virome configurations associated with IBD, and to uncover how those configurations are associated with therapeutic success.

METHODS: VLP enrichment followed by deep sequencing was performed on 432 faecal samples from 181 IBD patients starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into 'viral community types', respectively.

RESULTS: Patients were stratified based on unsupervised clustering into two viral community types. 'Community type CA' showed a low α-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated with the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Crassvirales and Malgrandaviricetes phages. During post-interventional analysis, endoscopic outcome was associated with gut virome composition. Remitting UC patients revealed a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Pre-interventional analyses also identified five novel phages associated with treatment success.

CONCLUSIONS: This study proposed two gut virome configurations that may be involved in the pathophysiology of IBD. Interestingly, those viral configurations are further associated with therapeutic success, suggesting a potential clinical relevance.}, } @article {pmid37049583, year = {2023}, author = {Hoelz, H and Heetmeyer, J and Tsakmaklis, A and Hiergeist, A and Siebert, K and De Zen, F and Häcker, D and Metwaly, A and Neuhaus, K and Gessner, A and Vehreschild, MJGT and Haller, D and Schwerd, T}, title = {Is Autologous Fecal Microbiota Transfer after Exclusive Enteral Nutrition in Pediatric Crohn's Disease Patients Rational and Feasible? Data from a Feasibility Test.}, journal = {Nutrients}, volume = {15}, number = {7}, pages = {}, pmid = {37049583}, issn = {2072-6643}, mesh = {Humans ; Child ; *Fecal Microbiota Transplantation ; *Enteral Nutrition ; RNA, Ribosomal, 16S/genetics ; Feasibility Studies ; Remission Induction ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is a highly effective therapy for remission induction in pediatric Crohn's disease (CD), but relapse rates after return to a regular diet are high. Autologous fecal microbiota transfer (FMT) using stool collected during EEN-induced clinical remission might represent a novel approach to maintaining the benefits of EEN.

METHODS: Pediatric CD patients provided fecal material at home, which was shipped at 4 °C to an FMT laboratory for FMT capsule generation and extensive pathogen safety screening. The microbial community composition of samples taken before and after shipment and after encapsulation was characterized using 16S rRNA amplicon sequencing.

RESULTS: Seven pediatric patients provided fecal material for nine test runs after at least three weeks of nutritional therapy. FMT capsules were successfully generated in 6/8 deliveries, but stool weight and consistency varied widely. Transport and processing of fecal material into FMT capsules did not fundamentally change microbial composition, but microbial richness was <30 genera in 3/9 samples. Stool safety screening was positive for potential pathogens or drug resistance genes in 8/9 test runs.

CONCLUSIONS: A high pathogen burden, low-diversity microbiota, and practical deficiencies of EEN-conditioned fecal material might render autologous capsule-FMT an unsuitable approach as maintenance therapy for pediatric CD patients.}, } @article {pmid37048642, year = {2023}, author = {Shaikh, SD and Sun, N and Canakis, A and Park, WY and Weber, HC}, title = {Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {7}, pages = {}, pmid = {37048642}, issn = {2077-0383}, abstract = {Irritable Bowel Syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits. It has a prevalence of 10 to 25% in the United States and has a high disease burden, as evidenced by reduced quality of life, decreased work productivity and increased healthcare utilization and costs. IBS has been associated with several intra-intestinal and extra-intestinal conditions, including psychiatric comorbidities. Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain-gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition. The purpose of this article is to review the role the gut microbiota plays in the pathophysiology of IBS, understand factors that affect the gut microbiome and explore the microbiome as a target of treatment.}, } @article {pmid37047094, year = {2023}, author = {Del Barrio, M and Lavín, L and Santos-Laso, Á and Arias-Loste, MT and Odriozola, A and Rodriguez-Duque, JC and Rivas, C and Iruzubieta, P and Crespo, J}, title = {Faecal Microbiota Transplantation, Paving the Way to Treat Non-Alcoholic Fatty Liver Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, doi = {10.3390/ijms24076123}, pmid = {37047094}, issn = {1422-0067}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease (CLD). Currently, the only therapeutic recommendation available is a lifestyle change. However, adherence to this approach is often difficult to guarantee. Alteration of the microbiota and an increase in intestinal permeability seem to be key in the development and progression of NAFLD. Therefore, the manipulation of microbiota seems to provide a promising therapeutic strategy. One way to do so is through faecal microbiota transplantation (FMT). Here, we summarize the key aspects of FMT, detail its current indications and highlight the most recent advances in NAFLD.}, } @article {pmid37046762, year = {2023}, author = {Kiousi, DE and Kouroutzidou, AZ and Neanidis, K and Karavanis, E and Matthaios, D and Pappa, A and Galanis, A}, title = {The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions.}, journal = {Cancers}, volume = {15}, number = {7}, pages = {}, doi = {10.3390/cancers15072101}, pmid = {37046762}, issn = {2072-6694}, abstract = {Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome-immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.}, } @article {pmid37046603, year = {2023}, author = {Yang, Q and Wei, Y and Zhu, Y and Guo, J and Zhang, J and He, Y and Li, X and Liu, J and Zhou, W}, title = {The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma.}, journal = {Cancers}, volume = {15}, number = {7}, pages = {}, doi = {10.3390/cancers15071942}, pmid = {37046603}, issn = {2072-6694}, abstract = {Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota-host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.}, } @article {pmid37041839, year = {2023}, author = {Syafruddin, S and Siregar, TN and Wahyuni, S and Gholib, G and Pulungan, ILC and Muchsalmina, M}, title = {Transplantation of Aceh cattle ovary into the uterus of pseudopregnant local rabbits: Effect of post-transplant stress on uterine histopathology and ovarian follicle dynamics.}, journal = {Veterinary world}, volume = {16}, number = {3}, pages = {500-508}, pmid = {37041839}, issn = {0972-8988}, abstract = {BACKGROUND AND AIM: The increase in the levels of the cortisol hormone caused by the stress conditions generated by an ovary transplantation procedure can damage the uterus of the transplant recipient as well as the transplanted ovaries. This study aimed to analyze the histopathological changes that occur in the uterine horn of pseudopregnant local rabbits (recipients), as well as the ovarian follicular integrity of the donor Aceh cattle after transplantation.

MATERIALS AND METHODS: After 30 days of adaptation, all rabbits were divided into three treatment groups: R1 (the group of rabbits that underwent ovarian transplantation for 3 days, n = 5), R2 (the group of rabbits that underwent ovarian transplantation for 5 days, n = 5), and R3 (the group of rabbits that underwent ovarian transplantation for 7 days, n = 5). Pseudopregnancy induction was performed using the pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) methods. The rabbits were injected with 100 IU of PMSG intramuscularly, followed by an injection of 75 IU of hCG intravenously 3 days later. Ovarian transplantation was performed on day 8 (day 0 was the day of hCG injection). The concentration of cortisol hormone metabolites was measured from fecal samples using an enzyme-linked immunosorbent assay technique. The uterus and ovaries were collected for histopathological and follicular dynamics examination after the transplantation process was completed.

RESULTS: The mean cortisol levels (ng/g) recorded before versus after the transplant in the R1, R2, and R3 groups were 146.23 ± 17.60 versus 338.84 ± 302.79, 128.97 ± 81.56 versus 174.79 ± 101.70, and 124.88 ± 43.61 versus 321.91 ± 221.63 (p < 0.05), respectively. The examination of the histopathological appearance of the uterus revealed edema in the uterine lumen, hyperemia and hemorrhage in the endometrium, necrosis of the epithelium, and infiltration of inflammatory cells. Hemorrhage and hyperemia were severe and filled the endometrium in the R1 compared with the R2 and R3 animals. Ovarian follicle development occurred in all treatment groups, although some histopathological features were observed. The number of tertiary follicles in R1, R2, and R3 animals was 24.67 ± 7.37, 20.67 ± 7.57, and 9.67 ± 3.79 (p < 0.05), respectively.

CONCLUSION: Based on the results of this study, it can be concluded that the transplantation of ovaries from Aceh cattle into pseudopregnant local rabbits triggered an increase in the levels of the cortisol hormone and uterine histological changes; however, follicles were still detected at various stages of development in the transplanted Aceh cattle ovaries. The results of this study are valuable for clinicians and researchers because they provide information regarding an alternative in vivo ovarian preservation technique using pseudopregnant rabbits.}, } @article {pmid37039469, year = {2023}, author = {Luo, ZB and Han, S and Yin, XJ and Liu, H and Wang, J and Xuan, M and Hao, C and Wang, D and Liu, Y and Chang, S and Li, D and Gao, K and Li, H and Quan, B and Quan, LH and Kang, JD}, title = {Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, doi = {10.7554/eLife.81858}, pmid = {37039469}, issn = {2050-084X}, abstract = {The host genome may influence the composition of the intestinal microbiota, and the intestinal microbiota has a significant effect on muscle growth and development. In this study, we found that the deletion of the myostatin (MSTN) gene positively regulates the expression of the intestinal tight junction-related genes TJP1 and OCLN through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of MSTN[-/-] pigs differed from wild-type, including by the presence of a thicker muscularis and longer plicae. Together, these changes affect the structure of intestinal microbiota. Mice transplanted with the intestinal microbiota of MSTN[-/-] pigs had myofibers with larger cross-sectional areas and higher fast-twitch glycolytic muscle mass. Microbes responsible for the production of short-chain fatty acids (SCFAs) were enriched in both the MSTN[-/-] pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We also demonstrated that valeric acid stimulates type IIb myofiber growth by activating the Akt/mTOR pathway via G protein-coupled receptor 43 and ameliorates dexamethasone-induced muscle atrophy. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.}, } @article {pmid37038710, year = {2023}, author = {Peng, Y and Huang, J and Chen, J and Zhang, B and Liao, L and Zeng, L}, title = {Interaction Between the Intestinal Microbial Structure and Function Dysbiosis and Hippocampal Transcriptome Profile for Anxiety-like Induced by Doxorubicin in Mice.}, journal = {Combinatorial chemistry & high throughput screening}, volume = {}, number = {}, pages = {}, doi = {10.2174/1386207326666230406081822}, pmid = {37038710}, issn = {1875-5402}, abstract = {BACKGROUND: Cancer patients can have psychological disorders such as anxiety after chemotherapy, which severely influence their quality of life.

OBJECTIVE: In this study, we aimed to explore the relationship between the gene expression level and the gut microbiota composition/function for anxiety-like behavior induced by doxorubicin.

METHODS: C57BL/6J mice were intraperitoneally injected with 2.5 mg/kg doxorubicin once a week for 4 weeks and constructed a mouse model that mice transplanted fecal microbiota of doxorubicin-treated mice. The elevated Plus Maze (EPM) and Open Field Test (OFT) assessed anxiety-like behaviors. 16S rRNA gene sequencing of fecal samples was used to explore the intestinal microbial structure and function. RNA-sequencing of the hippocampus explored the underlying mechanisms and transcriptional changes.

RESULTS: Treatment with doxorubicin and fecal microbiota transplantation (FMT) produced anxiety-like behavior in mice. 16S rRNA fecal sequencing revealed differences in microbial composition between the vehicle groups (Veh) and doxorubicin groups (Dox). COG analyses showed that the Dox mice displayed decreased clusters of Carbohydrate transport and metabolism, transcription, signal transduction mechanism and defense mechanisms from the Veh mice. RNA-sequencing analysis showed that the 22 significantly differentially expressed genes DEGs. Spearman correlation analysis indicated 22 DEGs were associated with the different bacteria flora between the two groups.

CONCLUSION: Overall, our data illustrated that the intestinal microbial structure and function dysbiosis is associated with the anxiety-like behavior induced by doxorubicin and hippocampal gene expression. And supported the microbiota regulation as a therapeutic approach for the treatment of neurogenic disease.}, } @article {pmid37036515, year = {2023}, author = {Liu, J and Chen, H and Yu, T and Fu, X and Qian, C and Feng, X}, title = {Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice.}, journal = {Aging}, volume = {15}, number = {}, pages = {}, doi = {10.18632/aging.204642}, pmid = {37036515}, issn = {1945-4589}, abstract = {BACKGROUND: Neuroinflammation is a frequent cause of brain damage after intracerebral hemorrhage (ICH). Gut microbiota are reported to regulate neuroinflammation. Berberine has been found to have anti-inflammatory actions, including in the central nervous system. However, it is not known whether berberine regulates neuroinflammation after ICH, nor is the relationship between the antineuroinflammatory actions of berberine and the gut microbiota after ICH understood.

METHODS: ICH was induced in male mice by collagenase injection. Immunofluorescent staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect microglia/macrophage phenotypes. Immunofluorescent staining, ELISA, and FITC-dextran were conducted to determine gut function. 16S rRNA sequencing of the fecal material was conducted to determine alterations in the gut microbiota. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to deplete or restore the gut microbiota, respectively. Cylinder, forelimb placement and wire hanging tests were conducted to evaluate neurobehavioral function.

RESULTS: Berberine significantly reduced neuroinflammation and alleviated neurological dysfunction by preventing microglial/macrophage proinflammatory polarization in ICH mice. Berberine also enhanced the function of the intestinal barrier, as shown by reductions in the levels of lipopolysaccharide-binding protein. Neuroinflammation in ICH mice was markedly reduced after transplantation of microbiota from berberine-treated mice, similar to treatment with oral berberine. In addition, a reduction in the microbiota reversed the neuroprotective effect of berberine.

CONCLUSIONS: Berberine is a potential treatment for ICH-induced neuroinflammation, and its effects are at least partially dependent on the gut microbiota.}, } @article {pmid37030333, year = {2023}, author = {Liu, Y and Li, J and Kang, W and Liu, S and Liu, J and Shi, M and Wang, Y and Liu, X and Chen, X and Huang, K}, title = {Aflatoxin B1 induces liver injury by disturbing gut microbiota-bile acid-FXR axis in mice.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {113751}, doi = {10.1016/j.fct.2023.113751}, pmid = {37030333}, issn = {1873-6351}, abstract = {Aflatoxin B1 (AFB1) is one of major pollutant in food and feed worldwide. The purpose of this study is to investigate the mechanism of AFB1-induced liver injury. Our results showed that AFB1 caused hepatic bile duct proliferation, oxidative stress, inflammation and liver injury in mice. AFB1 exposure induced gut microbiota dysbiosis and reduced fecal bile salt hydrolase (BSH) activity. AFB1 exposure promoted hepatic bile acid (BA) synthesis and changed intestinal BA metabolism, especially increased intestinal conjugated bile acids levels. AFB1 exposure inhibited intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) signaling. Furthermore, the mice received fecal microbiota transplantation from AFB1-treated mice induced liver injury, reduced intestinal FXR signaling and increased hepatic BA synthesis. Finally, the intestine-restricted FXR agonist treatment decreased hepatic BA synthesis, ROS level, inflammation and liver injury in AFB1-treated mice. This study suggests that modifying the gut microbiota, altering intestinal BA metabolism and/or activating intestinal FXR/FGF-15 signaling may be of value for the treatment of AFB1-induced liver disease.}, } @article {pmid37029815, year = {2023}, author = {Shatila, M and Ma, W and Cui, Y and Naz, S and S Thomas, A and N De Toni, E and Török, HP and Khaled, NB and Altan, M and Schneider, B and Wang, Y}, title = {Effects of immunosuppressive treatment on patient outcomes after immune checkpoint inhibitor-related gastrointestinal toxicity.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37029815}, issn = {1432-1335}, abstract = {PURPOSE: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS).

METHODS: This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1 year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26.

RESULTS: Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p < 0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p < 0.05). Immunosuppression has no effect on PFS (p < 0.05).

CONCLUSION: Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.}, } @article {pmid37022735, year = {2023}, author = {Pietras, EM}, title = {Young bugs rejuvenate old blood.}, journal = {Blood}, volume = {141}, number = {14}, pages = {1650-1652}, doi = {10.1182/blood.2023019638}, pmid = {37022735}, issn = {1528-0020}, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cells ; Inflammation ; }, } @article {pmid37022171, year = {2023}, author = {Hankir, MK and Kovatcheva-Datchary, P and Springer, R and Hoffmann, A and Vogel, J and Seyfried, F and Arora, T}, title = {Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0510922}, doi = {10.1128/spectrum.05109-22}, pmid = {37022171}, issn = {2165-0497}, abstract = {Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.}, } @article {pmid37020579, year = {2023}, author = {Di Pietro, R and Arroyo, LG and Leclere, M and Costa, M}, title = {Effects of concentrated fecal microbiota transplant on the equine fecal microbiota after antibiotic-induced dysbiosis.}, journal = {Canadian journal of veterinary research = Revue canadienne de recherche veterinaire}, volume = {87}, number = {2}, pages = {85-96}, pmid = {37020579}, issn = {1928-9022}, mesh = {Horses ; Animals ; Fecal Microbiota Transplantation/methods/veterinary ; Anti-Bacterial Agents ; Dysbiosis/microbiology/veterinary ; Treatment Outcome ; Feces/microbiology ; *Microbiota ; Bacteria ; *Horse Diseases ; }, abstract = {Bacterial imbalances are observed in intestinal diseases and fecal microbiota transplantation (FMT) has been used to restore the intestinal microbiota of horses. However, there is evidence that the current methods proposed for FMT in horses have limited efficacy. The objective of this study was to concentrate the bacteria present in the donor stool by centrifugation, and to test the effect in horses with antibiotic-induced dysbiosis. One healthy 11-year-old horse was selected as a fecal donor and 9 horses were given trimethoprim sulfadiazine (TMS) for 5 days to induce dysbiosis. Horses received either a concentrated FMT (cFMT, n = 3), fresh unconcentrated FMT (fFMT, n = 3), or 10% glycerol solution (vehicle, VEH, n = 3) by nasogastric tube for 3 days. Fecal samples were collected on Days 0, 4, 9, 11, and 21 for microbiota analysis (Illumina sequencing). The TMS significantly changed the bacterial composition of horses' feces (D0 versus D4). The composition of the cFMT and fFMT recipient horses was significantly different after transplantation compared to after antibiotic-induced dysbiosis (D4 versus D11), whereas the microbiota of the vehicle recipients was not, indicating that both protocols induced transient changes. However, preparation of FMT solutions markedly changed the original composition present in the donor's feces, with significant enrichment of Escherichia genus in the cFMT. Individual susceptibility to restoration of the microbiota was observed in horses, similar to what is known for other species. Our results suggest that concentrating bacteria should not be recommended in preparation of FMT solutions and that further research is required to improve current methods recommended to perform FMT in horses.}, } @article {pmid37019989, year = {2023}, author = {Nemoto, S and Kubota, T and Ohno, H}, title = {Exploring body weight-influencing gut microbiota by elucidating the association with diet and host gene expression.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5593}, pmid = {37019989}, issn = {2045-2322}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Obesity/metabolism ; Weight Gain ; Diet, High-Fat ; Gene Expression ; *Insulins ; Mice, Inbred C57BL ; }, abstract = {We aimed to identify gut microbiota that influences body weight by elucidating the association with diets and host genes. Germ-free (GF) mice with and without fecal microbiota transplant (FMT) were fed a normal, high-carbohydrate, or high-fat diet. FMT mice exhibited greater total body weight; adipose tissue and liver weights; blood glucose, insulin, and total cholesterol levels; and oil droplet size than the GF mice, regardless of diet. However, the extent of weight gain and metabolic parameter levels associated with gut microbiota depended on the nutrients ingested. For example, a disaccharide- or polysaccharide-rich diet caused more weight gain than a monosaccharide-rich diet. An unsaturated fatty acid-rich diet had a greater microbial insulin-increasing effect than a saturated fatty acid-rich diet. Perhaps the difference in microbial metabolites produced from substances taken up by the host created metabolic differences. Therefore, we analyzed such dietary influences on gut microbiota, differentially expressed genes between GF and FMT mice, and metabolic factors, including body weight. The results revealed a correlation between increased weight gain, a fat-rich diet, increased Ruminococcaceae abundance, and decreased claudin 22 gene expression. These findings suggest that weight regulation might be possible through the manipulation of the gut microbiota metabolism using the host's diet.}, } @article {pmid37019893, year = {2023}, author = {Panebianco, C and Pisati, F and Villani, A and Andolfo, A and Ulaszewska, M and Bellini, E and Ferro, C and Lombardi, R and Orsenigo, F and Latiano, TP and Belmonte, B and Tripodo, C and Perri, F and Pazienza, V}, title = {Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRAS[G12D] mutated pancreatic cancer in vivo model.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {116}, pmid = {37019893}, issn = {2058-7716}, abstract = {Pancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients' quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice' serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients' quality of life and to increase the chance of cure.}, } @article {pmid37019665, year = {2023}, author = {Ka, Y and Ito, R and Nozu, R and Tomiyama, K and Ueno, M and Ogura, T and Takahashi, R}, title = {Establishment of a human microbiome- and immune system-reconstituted dual-humanized mouse model.}, journal = {Experimental animals}, volume = {}, number = {}, pages = {}, doi = {10.1538/expanim.23-0025}, pmid = {37019665}, issn = {1881-7122}, abstract = {Humanized mice are widely used to study the human immune system in vivo and investigate therapeutic targets for various human diseases. Immunodeficient NOD/Shi-scid-IL2rγ[null] (NOG) mice transferred with human hematopoietic stem cells are a useful model for studying human immune systems and analyzing engrafted human immune cells. The gut microbiota plays a significant role in the development and function of immune cells and the maintenance of immune homeostasis; however, there is currently no available animal model that has been reconstituted with human gut microbiota and immune systems in vivo. In this study, we established a new model of CD34[+] cell-transferred humanized germ-free NOG mice using an aseptic method. Flow cytometric analysis revealed that the germ-free humanized mice exhibited a lower level of human CD3[+] T cells than the SPF humanized mice. Additionally, we found that the human CD3[+] T cells slightly increased after transplanting human gut microbiota into the germ-free humanized mice, suggesting that the human microbiota supports T cell proliferation or maintenance in humanized mice colonized by the gut microbiota. Consequently, the dual-humanized mice may be useful for investigating the physiological role of the gut microbiota in human immunity in vivo and for application as a new humanized mouse model in cancer immunology.}, } @article {pmid37012144, year = {2023}, author = {Emile, SH and Garoufalia, Z and Barsom, S and Horesh, N and Gefen, R and Zhou, P and Wexner, SD}, title = {Systematic review and meta-analysis of randomized clinical trials on the treatment of low anterior resection syndrome.}, journal = {Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.surg.2023.02.010}, pmid = {37012144}, issn = {1532-7361}, abstract = {BACKGROUND: We conducted a systematic review of randomized clinical trials on treating low anterior resection syndrome to help inform current practice.

METHODS: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of randomized clinical trials involved different treatments for low anterior resection syndrome. The risk of bias 2 tool was used to assess the risk of bias. The main outcomes were improvement in low anterior resection syndrome after treatment assessed by change in low anterior resection syndrome, fecal incontinence scores, and adverse treatment effects.

RESULTS: After an initial screening of 1,286 studies, 7 randomized clinical trials were included. Sample sizes ranged between 12 to 104 patients. Posterior tibial nerve stimulation was the most frequently assessed treatment in 3 randomized clinical trials. The weighted mean difference between posterior tibial nerve stimulation and medical treatment or sham therapy in follow-up low anterior resection syndrome score (-3.31, P = .157) was insignificant. Transanal irrigation reduced major low anterior resection syndrome symptoms by 61.5% compared with 28.6% after posterior tibial nerve stimulation with a significantly lower 6-month follow-up low anterior resection syndrome score. Pelvic floor training achieved better improvement in low anterior resection syndrome than standard care (47.8% vs 21.3%) at 6 months, but this was not maintained at 12 months (40.0% vs 34.9%). Ramosetron was associated with a greater short-term improvement in major low anterior resection syndrome (23% vs 8%) and a lower low anterior resection syndrome score (29.5 vs 34.6) at 4-weeks follow-up than Kegels or Sitz baths. No significant improvement in bowel function was noted after probiotics use as probiotics and placebo had similar follow-up low anterior resection syndrome scores (33.3 vs 36).

CONCLUSION: Transanal irrigation was associated with improvement in low anterior resection syndrome according to 2 trials, and ramosetron showed promising short-term results in one trial. Posterior tibial nerve stimulation had a marginal benefit compared with standard care. In contrast, pelvic floor training was associated with short-term symptomatic improvement, and probiotics showed no tangible improvement in low anterior resection syndrome symptoms. Firm conclusions cannot be drawn due to the small number of trials published.}, } @article {pmid37011727, year = {2023}, author = {Gharaie, S and Lee, K and Newman-Rivera, AM and Xu, J and Patel, SK and Gooya, M and Arend, LJ and Raj, DS and Pluznick, J and Parikh, C and Noel, S and Rabb, H}, title = {Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis.}, journal = {Kidney international}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.kint.2023.03.024}, pmid = {37011727}, issn = {1523-1755}, abstract = {Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included the glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4[+]T cells, interleukin (IL)-17 [+]CD4[+]T cells, and tumor necrosis factor-α double negative T cells while it increased CD8[+]T cells and PD1[+]CD8[+]T cells. Amoxicillin also increased gut lamina propria CD4[+]T cells while decreasing CD8[+]T and IL-17[+]CD4[+]T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8[+]T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3[+]CD8[+]T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.}, } @article {pmid37010964, year = {2023}, author = {Klingensmith, NJ and Coopersmith, CM}, title = {Gut Microbiome in Sepsis.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {250-257}, pmid = {37010964}, issn = {1557-8674}, mesh = {Humans ; *Gastrointestinal Microbiome ; Intestinal Mucosa/microbiology ; *Probiotics ; Prebiotics ; Bacteria ; *Sepsis/therapy ; }, abstract = {Abstract The gut has been hypothesized to be the "motor" of multiple organ dysfunction in sepsis. Although there are multiple ways in which the gut can drive systemic inflammation, increasing evidence suggests that the intestinal microbiome plays a more substantial role than previously appreciated. An English language literature review was performed to summarize the current knowledge of sepsis-induced gut microbiome dysbiosis. Conversion of a normal microbiome to a pathobiome in the setting of sepsis is associated with worsened mortality. Changes in microbiome composition and diversity signal the intestinal epithelium and immune system resulting in increased intestinal permeability and a dysregulated immune response to sepsis. Clinical approaches to return to microbiome homeostasis may be theoretically possible through a variety of methods including probiotics, prebiotics, fecal microbial transplant, and selective decontamination of the digestive tract. However, more research is required to determine the efficacy (if any) of targeting the microbiome for therapeutic gain. The gut microbiome rapidly loses diversity with emergence of virulent bacteria in sepsis. Restoring normal commensal bacterial diversity through various therapies may be an avenue to improve sepsis mortality.}, } @article {pmid37010962, year = {2023}, author = {Gibson, GA and Owen, EJ}, title = {Non-Antibiotic Approaches to Infection that Preserve the Microbiome in Critically Ill Patients.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {284-291}, doi = {10.1089/sur.2023.020}, pmid = {37010962}, issn = {1557-8674}, abstract = {In critically ill patients, the gut microbiota is subjected to various factors including antimicrobial exposure, modified gastrointestinal transit, nutrition support, as well as infection, which may lead to dysbiosis during the intensive care unit and hospital stay. Dysbiosis occupies an increasingly important role in driving morbidity and perhaps mortality in the critically ill or injured. Given that antibiotics lead to dysbiosis, it is relevant to understand the range of non-antibiotic approaches to infection-including those related to multi-drug-resistant organisms-that may leave the microbiome unimpacted. These strategies most prominently include the elimination of unabsorbed antibiotic agents from the digestive tract, pro-/pre-/synbiotics, fecal microbiota transplant, selective digestive and oropharyngeal decontamination, phage therapy, anti-sense oligonucleotides, structurally nanoengineered antimicrobial peptide polymers, and vitamin C-based lipid nanoparticles for adoptive macrophage transfer. Herein, we review the rationale for these therapies, current data regarding their use in critically ill patients, and the therapeutic potential for strategies that are not yet deployed in human medical care.}, } @article {pmid37010243, year = {2023}, author = {}, title = {Corrigendum: Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {37010243}, issn = {2542-5641}, } @article {pmid37009327, year = {2023}, author = {Jeyaraman, M and Nallakumarasamy, A and Jain, VK}, title = {Gut Microbiome - Should we treat the gut and not the bones?.}, journal = {Journal of clinical orthopaedics and trauma}, volume = {39}, number = {}, pages = {102149}, pmid = {37009327}, issn = {0976-5662}, abstract = {Gut microbiome (GM) forms an integral part of homeostasis of an individual. Due to the recent development of metagenomics, the plausibility of sequencing GM and its therapeutic ability for various diseases has been explored. Dysbiosis or disequilibrium or pertubations of GM leads to disruption of intercommunication signaling among gut-bone axis, gut-bone-brain axis, and gut-disc axis resulting in the progression of various chronic diseases. The therapeutic interventions to restore the GM like prebiotics and probiotics, bacteriophage therapy, fecal microbiota transplantation, and physical biomodulation have been identified. This review throw the lime light on the effect of gut dysbiosis in musculoskeletal diseases.}, } @article {pmid37008345, year = {2023}, author = {Larsen, C and Andersen, AB and Sato, H and Brunse, A and Thymann, T}, title = {Transplantation of fecal filtrate to neonatal pigs reduces post-weaning diarrhea: A pilot study.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1110128}, pmid = {37008345}, issn = {2297-1769}, abstract = {Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07[*]10[-9]), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size.}, } @article {pmid37005752, year = {2023}, author = {Gao, J and Chen, H and Xu, L and Li, S and Yan, H and Jiang, L and Cheng, W and Jiang, Z}, title = {Effects of Intestinal Microorganisms on Influenza-Infected Mice with Antibiotic-Induced Intestinal Dysbiosis, through the TLR7 Signaling Pathway.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {3}, pages = {43}, doi = {10.31083/j.fbl2803043}, pmid = {37005752}, issn = {2768-6698}, abstract = {BACKGROUND: Stability of intestinal flora is not only important for maintaining stable immune functions; it is also a key immune channel communicating the interaction between lung and intestine. In this study, probiotics and fecal microbiota transplantation (FMT) were used to regulate influenza-infected mice with antibiotic-induced intestinal dysbiosis and the effects of intestinal microorganisms on these mice were subsequently observed and evaluated.

METHODS: Mice are housed in a normal environment with intranasal infection with influenza virus (FM1). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine messenger RNA expression and lung viral replication of toll-like receptor 7 (TLR7), myeloid differentiation primary reaction 88 (MyD88) and nuclear factor κB (ss) p65 in the TLR7 signaling pathway. Western blotting is used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T regulated cells.

RESULTS: Results showed that compared with the simple virus group, both diversity and species of intestinal flora in influenza-infected mice with antibiotic-induced intestinal dysbiosis were lower, in vivo viral replication was significantly increased, lung and intestinal tissues were seriously damaged, degree of inflammation increased, expression of the TLR7 signaling pathway increased, and the Th1/Th2:Th17/Treg ratio decreased. Probiotics and FMT effectively regulated intestinal flora, improved pathological lung changes and inflammation caused by influenza infection, and adjusted the TLR7 signaling pathway and the Th1/Th2:Th17/Treg ratio. This effect was not obvious in TLR7-⁣/- mice.In summary, by affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora.

CONCLUSIONS: By affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. In summary, damage to lung tissue and intestinal mucosa in influenza-infected mice with antibiotic-induced intestinal dysbiosis is more serious compared to simple virus-infected mice. Improving intestinal flora using probiotics or FMT can alleviate intestinal inflammation and improve pulmonary inflammation through the TLR7 signaling pathway.}, } @article {pmid37004699, year = {2023}, author = {He, Z and Liu, Y and Li, Z and Sun, T and Li, Z and Manyande, A and Xiang, H and Xiong, J}, title = {Gut microbiota regulates circadian oscillation in hepatic ischemia-reperfusion injury-induced cognitive impairment by interfering with hippocampal lipid metabolism in mice.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {37004699}, issn = {1936-0541}, abstract = {BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment.

METHODS: HIRI murine models were established by ischemia-reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis.

RESULTS: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences.

CONCLUSIONS: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism.}, } @article {pmid37003055, year = {2023}, author = {Jamal, R and Messaoudene, M and de Figuieredo, M and Routy, B}, title = {Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology.}, journal = {Seminars in immunology}, volume = {67}, number = {}, pages = {101754}, doi = {10.1016/j.smim.2023.101754}, pmid = {37003055}, issn = {1096-3618}, abstract = {The gut microbiota has rapidly emerged as one of the "hallmarks of cancers" and a key contributor to cancer immunotherapy. Metagenomics profiling has established the link between microbiota compositions and immune checkpoint inhibitors response and toxicity, while murine experiments demonstrating the synergistic benefits of microbiota modification with immune checkpoint inhibitors (ICIs) pave a clear path for translation. Fecal microbiota transplantation (FMT) is one of the most effective treatments for patients with Clostridioides difficile, but its utility in other disease contexts has been limited. Nonetheless, promising data from the first trials combining FMT with ICIs have provided strong clinical rationale to pursue this strategy as a novel therapeutic avenue. In addition to the safety considerations surrounding new and emerging pathogens potentially transmissible by FMT, several other challenges must be overcome in order to validate the use of FMT as a therapeutic option in oncology. In this review, we will explore how the lessons learned from FMT in other specialties will help shape the design and development of FMT in the immuno-oncology arena.}, } @article {pmid37001978, year = {2023}, author = {Xu, Z and Mak, JWY and Lin, Y and Yang, K and Liu, Q and Zhang, F and Lau, L and Tang, W and Ching, JY and Tun, HM and Chan, P and Chan, FKL and Ng, SC}, title = {Mixed-donor faecal microbiota transplantation was associated with increased butyrate-producing bacteria for obesity.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-328993}, pmid = {37001978}, issn = {1468-3288}, } @article {pmid37001737, year = {2023}, author = {Camilleri, M and Dilmaghani, S}, title = {Update on treatment of abdominal pain in irritable bowel syndrome: A narrative review.}, journal = {Pharmacology & therapeutics}, volume = {}, number = {}, pages = {108400}, doi = {10.1016/j.pharmthera.2023.108400}, pmid = {37001737}, issn = {1879-016X}, abstract = {The objectives of this narrative review are to update readers on the current state-of-the-art regarding diverse approaches for the treatment of pain, global symptoms, or adequate relief in irritable bowel syndrome (IBS). The article appraises medications, dietary interventions including low fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAP) diet, fecal microbial transplantation (FMT), electrical approaches, and behavioral therapies including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), mindfulness, and open-label placebo. Current evidence demonstrates only modest benefit in global IBS symptoms and pain relief. A future approach that identifies pathophysiological mechanisms of IBS through validated biomarkers has the potential to individualize treatment of patients rather than sequential therapeutic trial and error approaches.}, } @article {pmid36997133, year = {2023}, author = {Li, MY and Wu, YZ and Qiu, JG and Lei, JX and Li, MX and Xu, N and Liu, YH and Jin, Z and Su, ZR and Lee, SM and Zheng, XB and Xiao-Qi, H}, title = {Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116430}, doi = {10.1016/j.jep.2023.116430}, pmid = {36997133}, issn = {1872-7573}, abstract = {Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC).

AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization.

MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model.

RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4.

CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.}, } @article {pmid36996849, year = {2023}, author = {Zhang, Y and Sun, Y and Liu, Y and Liu, J and Sun, J and Liu, X and Fan, B and Lu, C and Wang, F}, title = {Polygonum sibiricum polysaccharides exert the antidepressant-like effects in chronic unpredictable mild stress-induced depressive mice by modulating microbiota-gut-brain axis.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.7813}, pmid = {36996849}, issn = {1099-1573}, abstract = {Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.}, } @article {pmid36994745, year = {2023}, author = {Yang, Z and Wang, Q and Liu, Y and Wang, L and Ge, Z and Li, Z and Feng, S and Wu, C}, title = {Gut microbiota and hypertension: association, mechanisms and treatment.}, journal = {Clinical and experimental hypertension (New York, N.Y. : 1993)}, volume = {45}, number = {1}, pages = {2195135}, doi = {10.1080/10641963.2023.2195135}, pmid = {36994745}, issn = {1525-6006}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Risk Factors ; *Probiotics/therapeutic use ; }, abstract = {OBJECTIVES: Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes a major public health problem. At present, the pathogenesis of hypertension is unclear. Increasing evidence has proven that the pathogenesis of hypertension is closely related to the dysbiosis of gut microbiota. We briefly reviewed relevant literature on gut microbiota and hypertension to summarize the relationship between gut microbiota and hypertension, linked the antihypertension effects of drugs with their modulation on gut microbiota, and discussed the potential mechanisms of various gut microbes and their active metabolites to alleviate hypertension, thus providing new research ideas for the development of antihypertension drugs.

METHODS: The relevant literature was collected systematically from scientific database, including Elsevier, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of herbal medicine.

RESULTS: Hypertension can lead to gut microbiota imbalance and gut barrier dysfunction, including increased harmful bacteria and hydrogen sulfide and lipopolysaccharide, decreased beneficial bacteria and short-chain fatty acids, decreased intestinal tight junction proteins and increased intestinal permeability. Gut microbiota imbalance is closely related to the occurrence and development of hypertension. At present, the main methods to regulate the gut microbiota include fecal microbiota transplantation, supplementation of probiotics, antibiotics, diet and exercise, antihypertensive drugs, and natural medicines.

CONCLUSIONS: Gut microbiota is closely related to hypertension. Investigating the correlation between gut microbiota and hypertension may help to reveal the pathogenesis of hypertension from the perspective of gut microbiota, which is of great significance for the prevention and treatment of hypertension.}, } @article {pmid36993518, year = {2023}, author = {Hajjar, J and Voigt, A and Conner, M and Swennes, A and Fowler, S and Calarge, C and Mendonca, D and Armstrong, D and Chang, CY and Walter, J and Butte, M and Savidge, T and Oh, J and Kheradmand, F and Petrosino, J}, title = {Common Variable Immunodeficiency Patient Fecal Microbiota Transplant Recapitulates Gut Dysbiosis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-2640584/v1}, pmid = {36993518}, abstract = {Purpose Patients with non-infectious complications have worse clinical outcomes in common variable immunodeficiency (CVID) than those with infections-only. Non-infectious complications are associated with gut microbiome aberrations, but there are no reductionist animal models that emulate CVID. Our aim in this study was to uncover potential microbiome roles in the development of non-infectious complications in CVID. Methods We examined fecal whole genome shotgun sequencing from patients CVID, and non-infectious complications, infections-only, and their household controls. We also performed Fecal Microbiota transplant from CVID patients to Germ-Free Mice. Results We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with non-infectious complications. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus , known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of infections-only CVID patients. Fecal microbiota transplant from non-infectious complications, infections-only, and their household controls into germ-free mice revealed gut dysbiosis patterns in recipients from CVID patients with non-infectious complications, but not infections-only CVID, or household controls recipients. Conclusion Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with non-infectious complications to Germ-Free mice recapitulates microbiome alterations observed in the donors.}, } @article {pmid36993296, year = {2023}, author = {Chiaro, TR and Bauer, KM and Ost, KS and Stephen-Victor, E and Nelson, MC and Hill, JH and Bell, R and Harwood, M and Voth, W and Jackson, T and Klag, KA and Oâ Connell, RM and Zac Stephens, W and Round, JL}, title = {Clec12a tempers inflammation while restricting expansion of a colitogenic commensal.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.16.532997}, pmid = {36993296}, abstract = {Regulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a [-/-] mice that was marked by expansion of the gram-positive organism, Faecalibaculum rodentium . Treatment with F. rodentium was sufficient to worsen colitis in wild-type mice. Macrophages within the gut express the highest levels of Clec12a. Cytokine and sequencing analysis in Clec12a [-/-] macrophages revealed heighten inflammation but marked reduction in genes associated with phagocytosis. Indeed, Clec12a [-/-] macrophages are impaired in their ability to uptake F. rodentium. Purified Clec12a had higher binding to gram-positive organisms such as F. rodentium . Thus, our data identifies Clec12a as an innate immune surveillance mechanism to control expansion of potentially harmful commensals without overt inflammation.}, } @article {pmid36990700, year = {2023}, author = {, and , and , }, title = {[Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {46}, number = {4}, pages = {352-372}, doi = {10.3760/cma.j.cn112147-20221214-00971}, pmid = {36990700}, issn = {1001-0939}, abstract = {Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first batch of rare diseases in China in 2018. In recent years, CF has been gradually recognized in China, and the number of CF patients reported in China in the past 10 years is more than 2.5 times the total number in the previous 30 years, and the total number of CF patients is estimated to be more than 20 000. The research progress of CF gene modification has led to the innovation of CF treatment. However, the sweat test as an important test for the diagnosis of CF has not been widely implemented in China. At present, the diagnosis and treatment of CF in China still lacks standardized recommendations. In view of these updates, the Chinese Experts Cystic Fibrosis Consensus Committee has formed "the Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis" based on extensive opinion gathering, literatures review, multiple meetings and discussions. This consensus collects 38 core issues related to CF, including pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and patient management. Finally, 32 recommendations were formulated. The consensus used the modified GRADE methodology to grade the evidence evaluation and recommendations. This is the current state of CF consensus in China, and we hope to improve the diagnosis and treatment of CF in China in the future.Summary of recommendationsQuestion 1: How can CF be identified?CF should be suspected if there is: (1) a family history of CF; (2) delayed meconium expulsion or meconium ileus; (3) pancreatic exocrine insufficiency, mainly characterized by long-standing steatorrhea and malnutrition; (4) recurrent lower respiratory tract infections of infantile onset, especially Pseudomonas aeruginosa (PA), Staphylococcus aureus infections of respiratory aetiology; (5) chronic sinusitis, especially when combined with juvenile presentation of nasal polyps; (6) chest CT abnormalities such as the presence of air trapping, bronchiectasis (upper lobe predominant); (7) pseudo-Bartter syndrome; (8) absence of vas deferens in males; (9) clubbing in young bronchiectasis patients(1C).Question 2: What are the diagnostic criteria for CF?1.1 Presence of one or more of the characteristic clinical manifestations or family history consistent with CF, and meeting at least one of the following definite diagnostic criteria in 1.2 or 1.3.1.2 Sweat chloride testing:(1) Concentrations of more than 60 mmol/L are diagnostic; (2) concentrations between 30-59 mmol/L are intermediate, and genetic variation must be considered to confirm the diagnosis; (3) concentrations less than 30 mmol/L are considered normal.1.3 Genetic testing:(1) Detection of two disease-causing CFTR(cystic fibrosis transmembrane conductance regulator) mutations on biallelic alleles; (2) The CFTR variants are of undetermined significance, but tests such as sweat chloride concentration, intestinal current measurement, or nasal mucosal potential difference suggest abnormal CFTR function, then CF is diagnostic(1C).Question 3: What is the diagnostic process for CF arranged?Sweat chloride testing and CFTR gene analysis are recommended in all patients suspected of CF(1D).Question 4: What is the value of sweat chloride testing in the diagnosis of CF?Sweat chloride testing is the gold standard for the clinical diagnosis of CF(1C).Question 5: What is the value of CFTR genetic testing in Chinese CF diagnosis?Biallelic pathogenic variants of CFTR are a definitive diagnosis of CF(1D).Question 6: What is the diagnostic value of imaging for CF?Chest CT is a sensitive test for early stages of lung disease in patients with CF and is appropriate in younger patients and to assess disease progression. The imaging findings of abdominal visceral involvement in CF lack specificity(2C).Question 7: How to evaluate the pancreatic function of CF patients?Fecal elastase may be used as the first indicator to assess pancreatic exocrine function in patients with CF (2C).Question 8: How to diagnose hepatic abnormality of CF?CF related liver disease was diagnosed when CF was confirmed and 2 of the following 4 criteria were met: (1) hepatomegaly and/or splenomegaly confirmed by ultrasound; (2) ALT, AST, and GGT on three consecutive occasions above the upper limit of normal on three consecutive occasions for more than 12 months and excluding other causes; (3) had evidence of liver involvement, portal hypertension, or bile duct dilatation by ultrasound; (4) liver biopsy confirmation (focal biliary cirrhosis or multilobular cirrhosis) may be indicated if the diagnosis is suspected(2D).Question 9: How to identify pulmonary exacerbations in patients with CF?Pulmonary exacerbations are indicated when any 4 of the following 12 signs or symptoms are met: increased sputum; new onset haemoptysis or increased haemoptysis; exacerbation of cough; increased dyspnea; malaise, fatigue, or somnolence; body temperature above 38 ℃; anorexia or weight loss; sinus pain or tenderness; increased sinus secretions; new chest signs; FEV1≥10% decline from previous; imaging changes suggestive of pulmonary infection(2D).Question 10: How to diagnose CF related diabetes?Diagnostic criteria for CF related diabetes are the same as those for diabetes in the population(1D).Question 11: How to evaluate the nutritional status of CF patients?Anthropometric parameters reflecting nutritional status should be assessed regularly. And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C).Question 12: Does CF require pathological examination as a diagnostic basis?Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D).Question 13: Do CF patients need long-term macrolides?At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A).Question 14: Do CF patients need long-term inhalation of hypertonic saline?Long term treatment with hypertonic saline is recommended for patients with CF(1A).Question 15: Do CF patients need long-term inhalation of Dornase alfa(DNase)?Long term use of DNase is recommended in patients with CF aged 6 years and older(1A).Question 16: Do CF patients need inhalation of mannitol?Inhaled mannitol therapy is recommended for more than 6 months in patients with CF aged 18 years and older when other inhaled treatments are unavailable or intolerable(2A).Question 17: How to deal with PA found in the sputum culture of CF patients?When sputum cultures from patients with CF are positive for PA, it needs to determine the characteristics of the infection first. The purpose for acute infection is to eradicate PA. Chronic colonization does not need to be eradicated, and the main purpose is to reduce the bacterial load and improve symptoms(1A).Question 18: Do CF patients need inhalation of antibiotics?Inhaled antibiotic therapy is recommended for CF patients with PA infection(1A).Question 19: Do CF patients need inhaled or systemic corticosteroids?In patients with CF without asthma or ABPA, routine inhaled or systemic glucocorticoids are not recommended (2A).Question 20: Do CF patients need to inhale bronchodilators?Bronchodilators can be used in the short term to improve symptoms in patients with CF in the presence of airway obstruction, but the long-term benefit is insufficient (2B).Question 21: Do CF patients need expectorant medicine?Patients with CF can take acetylcysteine orally or aerosolized(2A).Question 22: How to deal with acute pulmonary exacerbation in CF patients?Intensive implementation of non-antimicrobial therapy is recommended during pulmonary exacerbations in patients with CF. Antimicrobials with activity against PA were selected for empirical treatment, and the treatment was adjusted according to the results of bacterial culture and drug susceptibility testing. A 21-day long course of anti-infective therapy is not recommended(1B).Question 23: How to treat CF patients with ABPA?Medical therapy is recommended for CF patients with ABPA who meet any of the following criteria: patients with elevated immunoglobulin E levels and concomitant worsening of pulmonary function and/or pulmonary symptoms, or imaging suggesting new infiltrative foci in the chest(1D).Glucocorticoids are recommended for ABPA exacerbations in CF patients without contraindications(2D).Itraconazole should be added if the patient presents with poor response to corticosteroids, recurrence of ABPA, corticosteroid dependence, or corticosteroid toxicity(2D).Question 24: Is lung transplantation recommended for patients with CF? When is it recommended?Patients with CF may be evaluated for lung transplantation when they meet the following criteria after optimal medical therapy: (1) FEV1<30% predicted; (2) FEV1<40% predicted (<50% predicted in children) with the following: 6-minute walk distance<400 meters; PaCO2>50 mmHg(1 mmHg=0.133 kPa); hypoxia at rest or after activity; pulmonary artery pressure measured by cardiotocography>50 mmHg or right heart dysfunction; continued deterioration despite aggressive supplementation of nutritional support; two exacerbations requiring intravenous antibiotic therapy per year; massive hemoptysis (>240 ml) requiring pulmonary artery embolization; presented with pneumothorax; (3) FEV1<50% predicted and rapid decline in lung function or rapid worsening of symptoms; (4) Presented with an acute exacerbation requiring positive pressure mechanical ventilation(2C).Question 25: How to deal with pancreatic disease in CF patients?Pancreatic enzyme replacement therapy is recommended in patients with CF pancreatic disease(1A).Question 26: How to deal with hepatobiliary disease in CF patients?Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B).Question 27: How to deal with gastrointestinal problems such as acid regurgitation in CF patients?Acid suppression is recommended for CF patients with gastrointestinal symptoms such as acid regurgitation (2B).Question 28: How to deal with CF related diabetes?Insulin therapy is recommended in CF related diabetes(1B).Question 29: How should nutritional support be given to patients with CF?Energy intake in patients with CF is recommended to be 110%-200% of the energy requirement of a healthy person under equivalent physiological conditions. And maintaining adequate protein, appropriate intake of fats, electrolytes, and fat-soluble vitamins are recommanded(1A).Question 30: How should respiratory rehabilitation be performed in patients with CF?Airway clearance therapy and appropriate exercise are recommended for patients with CF(1A).Question 31: What is included in the follow-up of CF patient?Patients with CF should have regular follow-up. Adult patients are recommended to be followed every 3-6 months, and children should be followed more frequently(2A).Question 32: How should CF patients avoid infections?Inpatients and outpatients are recommended to be separated according to microbiota carriage status(1D).Good hand hygiene is recommended for the patients with CF and their contacts(1D).It is recommended that CF patients wear masks in healthcare settings. This may reduce the release of potentially infectious aerosols during coughing (1D).Annual influenza vaccination is recommended for patients with CF>6 months of age and for all family members of patients with CF and all healthcare workers caring for these patients(2D).Palivizumab may be considered for the prevention of respiratory syncytial virus infection in patients with CF under two years of age(2A).}, } @article {pmid36990372, year = {2023}, author = {Guzzardi, MA and Rosa, F and Iozzo, P}, title = {Trust the gut: outcomes of gut microbiota transplant in metabolic and cognitive disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {105143}, doi = {10.1016/j.neubiorev.2023.105143}, pmid = {36990372}, issn = {1873-7528}, abstract = {Type 2 diabetes mellitus (T2DM) is a main public health concern, with increasing prevalence and growingly premature onset in children, in spite of emerging and successful therapeutic options. T2DM promotes brain aging, and younger age at onset is associated with a higher risk of subsequent dementia. Preventive strategies should address predisposing conditions, like obesity and metabolic syndrome, and be started from very early and even prenatal life. Gut microbiota is an emerging target in obesity, diabetes and neurocognitive diseases, which could be safely modulated since pregnancy and infancy. Many correlative studies have supported its involvement in disease pathophysiology. Faecal material transplantation (FMT) studies have been conducted in clinical and preclinical settings to deliver cause-effect proof and mechanistic insights. This review provides a comprehensive overview of studies in which FMT was used to cure or cause obesity, metabolic syndrome, T2DM, cognitive decline and Alzheimer's disease, including the evidence available in early life. Findings were analysed to dissect consolidated from controversial results, highlighting gaps and possible future directions.}, } @article {pmid36990294, year = {2023}, author = {Kralicek, SE and Jenkins, C and Allegretti, JR and Lewis, JD and Osman, M and Hecht, GA}, title = {Transmission of the potential pathogen atypical enteropathogenic E. coli by fecal microbiota transplant.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.03.222}, pmid = {36990294}, issn = {1528-0012}, } @article {pmid36986068, year = {2023}, author = {Rodriguez, DM and Hintze, KJ and Rompato, G and Stewart, EC and Barton, AH and Mortensen-Curtis, E and Green, PA and Van Wettere, AJ and Thomas, AJ and Benninghoff, AD}, title = {Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease.}, journal = {Nutrients}, volume = {15}, number = {6}, pages = {}, pmid = {36986068}, issn = {2072-6643}, mesh = {Mice ; Animals ; *Fecal Microbiota Transplantation ; *Colitis ; Carcinogenesis ; Cell Transformation, Neoplastic ; Inflammation ; Diet, Western ; Mice, Inbred C57BL ; }, abstract = {Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.}, } @article {pmid36749386, year = {2023}, author = {Tanaka, Y and Yamashita, R and Kawashima, J and Mori, H and Kurokawa, K and Fukuda, S and Gotoh, Y and Nakamura, K and Hayashi, T and Kasahara, Y and Sato, Y and Fukudo, S}, title = {Further notice of omics profiles of fecal and oral microbiota change in irritable bowel syndrome patients with diarrhea and symptom exacerbation.}, journal = {Journal of gastroenterology}, volume = {58}, number = {4}, pages = {427-428}, pmid = {36749386}, issn = {1435-5922}, mesh = {Humans ; *Irritable Bowel Syndrome/diagnosis ; Symptom Flare Up ; Diarrhea/etiology/diagnosis ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; }, } @article {pmid36990029, year = {2023}, author = {Hao, H and Li, Z and Qiao, SY and Qi, Y and Xu, XY and Si, JY and Liu, YH and Chang, L and Shi, YF and Xu, B and Wei, ZH and Kang, LN}, title = {Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora.}, journal = {Atherosclerosis}, volume = {371}, number = {}, pages = {32-40}, doi = {10.1016/j.atherosclerosis.2023.03.011}, pmid = {36990029}, issn = {1879-1484}, abstract = {BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora.

METHODS: Six-week-old male ApoE[-/-] mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE[-/-] mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses.

RESULTS: In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group.

CONCLUSIONS: Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.}, } @article {pmid36988432, year = {2023}, author = {Chen, LA and Oliva-Hemker, M and Radin, A and Weidner, M and O'Laughlin, BD and Sears, CL and Javitt, NB and Hourigan, SK}, title = {Longitudinal bile acid composition changes following fecal microbiota transplantation for Clostridioides difficile infection in children with and without underlying inflammatory bowel disease.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjad057}, pmid = {36988432}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplant (FMT) is effective in treating recurrent Clostridioides difficile infection (CDI) and restores gut microbiota composition. This unlikely accounts for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease (IBD).

METHODS: Eight children received FMT; five had underlying IBD. Primary and secondary fecal bile acids were measured by liquid chromatography-mass spectrometry in recipients (pre-FMT and longitudinally post-FMT for up to 6 months) and donors.

RESULTS: Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. While gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalization of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels.

CONCLUSIONS: The differences in bile acid profiles compared to gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts with longitudinal sampling to understand the mechanisms of FMT effectiveness.}, } @article {pmid36985379, year = {2023}, author = {Dossaji, Z and Khattak, A and Tun, KM and Hsu, M and Batra, K and Hong, AS}, title = {Efficacy of Fecal Microbiota Transplant on Behavioral and Gastrointestinal Symptoms in Pediatric Autism: A Systematic Review.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, doi = {10.3390/microorganisms11030806}, pmid = {36985379}, issn = {2076-2607}, abstract = {Background and Aims: There is a high prevalence of gastrointestinal-related (GI) symptoms among children with autism spectrum disorder (ASD), which is associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a proposed therapeutic strategy that aims to address the dysregulation of the gut microbiome among children with ASD. Our study performed the first systematic review aimed to evaluate the benefits of FMT on the behavioral and gastrointestinal symptoms of pediatric patients with autism. Methods: A literature search was performed using variations of the keywords "pediatrics" and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Web of Science from inception to 30 June 2022. Four studies that met the eligibility criteria were included in the systematic review. The efficacy of FMT on behavioral symptoms was measured by the difference in Aberrant Behavior Checklist (ABC) and Child Autism Rating Scale (CARS) scores before and after FMT. Results: We found a statistically significant improvement (p < 0.05) in ABC and CARS scores following FMT, with a statistically significant decrease in scores observed across all studies. In addition, substantial improvements in gastrointestinal symptoms were observed across all studies. Conclusion: Our findings suggest that FMT may offer a promising intervention for treating both behavioral and gastrointestinal symptoms in pediatric patients with autism.}, } @article {pmid36983718, year = {2023}, author = {Zhang, Z and Chen, H and Huang, J and Zhang, S and Li, Z and Kong, C and Mao, Y and Han, B}, title = {Early Administration of Vancomycin Inhibits Pulmonary Embolism by Remodeling Gut Microbiota.}, journal = {Journal of personalized medicine}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/jpm13030537}, pmid = {36983718}, issn = {2075-4426}, abstract = {Pulmonary embolism (PE) is a common and potentially fatal condition in the emergency department, and early identification of modifiable risk factors for prevention and management is highly desirable. Although gut dysbiosis is associated with a high incidence of venous thromboembolism, the role and mechanisms of the gut microbiome in the pathogenesis of venous thromboembolism, especially PE, remain unexplored. Here, we attempted to elucidate the benefits of the gut microbiome in the pathogenesis of PE using multiple antibiotics and fecal microbiota transplantation (FMT) for early intervention in a classical mouse model of PE. The results showed that early administration of various antibiotics (except ampicillin) could inhibit pulmonary thrombosis to a certain extent and reduced mortality in young and old mice with PE. Among them, vancomycin has the best inhibitory effect on PE. With the help of gut microbiota sequencing analysis, we found that antibiotic treatment can reshape the gut microbiota; especially vancomycin can significantly improve the gut microbiota structure in PE mice. Furthermore, FMT could transfer vancomycin-modified gut microbes into mice and inhibit the pathogenesis of PE, possibly due to increased intestinal colonization by Parasutterella. These data elucidate the underlying molecular mechanism by which early administration of vancomycin can remodel the gut microbiota to suppress PE, providing new clues for clinical optimization and development of PE prevention strategies.}, } @article {pmid36983199, year = {2023}, author = {Palumbo, VD and Tutino, R and Messina, M and Santarelli, M and Nigro, C and Lo Secco, G and Piceni, C and Montanari, E and Barletta, G and Venturelli, P and Geraci, G and Bonventre, S and Lo Monte, AI}, title = {Altered Gut Microbic Flora and Haemorrhoids: Could They Have a Possible Relationship?.}, journal = {Journal of clinical medicine}, volume = {12}, number = {6}, pages = {}, doi = {10.3390/jcm12062198}, pmid = {36983199}, issn = {2077-0383}, abstract = {To date, the exact pathophysiology of haemorrhoids is poorly understood. The different philosophies on haemorrhoids aetiology may lead to different approaches of treatment. A pathogenic theory involving a correlation between altered anal canal microflora, local inflammation, and muscular dyssynergia is proposed through an extensive review of the literature. Since the middle of the twentieth century, three main theories exist: (1) the varicose vein theory, (2) the vascular hyperplasia theory, and (3) the concept of a sliding anal lining. These phenomena determine changes in the connective tissue (linked to inflammation), including loss of organization, muscular hypertrophy, fragmentation of the anal subepithelial muscle and the elastin component, and vascular changes, including abnormal venous dilatation and vascular thrombosis. Recent studies have reported a possible involvement of gut microbiota in gut motility alteration. Furthermore, dysbiosis seems to represent the leading cause of bowel mucosa inflammation in any intestinal district. The alteration of the gut microbioma in the anorectal district could be responsible for haemorrhoids and other anorectal disorders. A deeper knowledge of the gut microbiota in anorectal disorders lays the basis for unveiling the roles of these various gut microbiota components in anorectal disorder pathogenesis and being conductive to instructing future therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in anorectal disorders.}, } @article {pmid36980767, year = {2023}, author = {Mareschal, J and Hemmer, A and Douissard, J and Dupertuis, YM and Collet, TH and Koessler, T and Toso, C and Ris, F and Genton, L}, title = {Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.}, journal = {Cancers}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/cancers15061881}, pmid = {36980767}, issn = {2072-6694}, abstract = {The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.}, } @article {pmid36979685, year = {2023}, author = {Piccioni, A and Rosa, F and Mannucci, S and Manca, F and Merra, G and Chiloiro, S and Candelli, M and Covino, M and Gasbarrini, A and Franceschi, F}, title = {Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship.}, journal = {Biomedicines}, volume = {11}, number = {3}, pages = {}, doi = {10.3390/biomedicines11030707}, pmid = {36979685}, issn = {2227-9059}, abstract = {There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation.}, } @article {pmid36977964, year = {2023}, author = {Balzano, T}, title = {Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed.}, journal = {Neurochemical research}, volume = {}, number = {}, pages = {}, pmid = {36977964}, issn = {1573-6903}, abstract = {Hepatic encephalopathy (HE) is a potentially reversible neurocognitive syndrome that occurs in patients with acute or chronic liver disease. Currently, most of the therapies for HE aim to reduce ammonia production or increase its elimination. To date, only two agents have been approved as treatments for HE: lactulose and rifaximin. Many other drugs have also been used, but data to support their use are limited, preliminary or lacking. The aim of this review is to provide an overview and discussion of the current development of treatments for HE. Data from ongoing clinical trials in HE were obtained from the ClinicalTrials.gov website, and a breakdown analysis of studies that were active on August 19th, 2022, was performed. Seventeen registered and ongoing clinical trials for therapeutics targeting HE were identified. More than 75% of these agents are in phase II (41.2%) or in phase III (34.7%). Among them, there are many old acquaintances in the field, such as lactulose and rifaximin, some new entries such as fecal microbiota transplantation and equine anti-thymocyte globulin, an immunosuppressive agent, but also some therapies borrowed from other conditions, such as rifamycin SV MMX and nitazoxanide, two antimicrobial agents FDA approved for the treatment of some types of diarrheas or VE303 and RBX7455, two microbiome restoration therapies, currently used as treatment of high-risk Clostridioides difficile infections. If working, some of these drugs could soon be used as valid alternatives to current therapies when ineffective or be approved as novel therapeutic approaches to improve the quality of life of HE patients.}, } @article {pmid36977440, year = {2023}, author = {Dang, Z and Gao, M and Wang, L and Wu, J and Guo, Y and Zhu, Z and Huang, H and Kang, G}, title = {Synthetic bacterial therapies for intestinal diseases based on quorum- sensing circuits.}, journal = {Biotechnology advances}, volume = {}, number = {}, pages = {108142}, doi = {10.1016/j.biotechadv.2023.108142}, pmid = {36977440}, issn = {1873-1899}, abstract = {Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.}, } @article {pmid36975808, year = {2023}, author = {Madden, GR and Rigo, I and Boone, R and Abhyankar, MM and Young, MK and Basener, W and Petri, WA}, title = {Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0009223}, doi = {10.1128/iai.00092-23}, pmid = {36975808}, issn = {1098-5522}, abstract = {Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold (CT) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT, endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.}, } @article {pmid36970196, year = {2023}, author = {Fan, X and Mai, C and Zuo, L and Huang, J and Xie, C and Jiang, Z and Li, R and Yao, X and Fan, X and Wu, Q and Yan, P and Liu, L and Chen, J and Xie, Y and Leung, EL}, title = {Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice.}, journal = {Acta pharmaceutica Sinica. B}, volume = {13}, number = {3}, pages = {1164-1179}, pmid = {36970196}, issn = {2211-3835}, abstract = {Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10[+] M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10[+] M2 macrophage production.}, } @article {pmid36969340, year = {2023}, author = {Tian, H and Wang, J and Feng, R and Zhang, R and Liu, H and Qin, C and Meng, L and Chen, Y and Fu, Y and Liang, D and Yuan, X and Zhai, Y and Zhu, Q and Jin, L and Teng, J and Ding, X and Wang, X}, title = {Efficacy of faecal microbiota transplantation in patients with progressive supranuclear palsy-Richardson's syndrome: a phase 2, single centre, randomised clinical trial.}, journal = {EClinicalMedicine}, volume = {58}, number = {}, pages = {101888}, pmid = {36969340}, issn = {2589-5370}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has demonstrated efficacy in treating gastrointestinal (GI) diseases, such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). GI dysfunction is a frequent and occasionally dominating symptom of progressive supranuclear palsy-Richardson's syndrome (PSP-RS). However, it is not known whether FMT has clinical efficacy for PSP-RS.

METHODS: This 36-week, randomised, placebo-controlled, parallel-group, phase 2 clinical trial was performed at a university tertiary referral hospital in China. From August 15 2021 to December 31 2021, a total of 68 newly diagnosed patients with PSP-RS (male 40 [59%], female 28 [41%]) who had never received any antiparkinsonian medications were enrolled and randomly assigned to receive either healthy donor FMT (n = 34, FMT group) or a mixture of 0.9% saline and food colouring (E150c) as sham transplantation (n = 34, placebo group) through transendoscopic enteral tubing (TET). Two days after oral antibiotics, participants received 1 week of transplantation. After an interval of 4 weeks, retransplantation was performed. Then, the last transplantation was given after another interval of 4 weeks, and the participants were followed up for 24 weeks (week 36). Clinicaltrials.gov identifier: ChiCTR-2100045397.

FINDINGS: Among 68 patients who were randomised (mean age, 67.2 (SD 5.1); 40 [59%] were male, 28 [41%] were female), 63 participants completed the trial. Efficacy analyses were performed on the intention-to-treat (ITT) analysis set. At week 16, the mean PSP Rating Scale (PSPRS) scores (the primary outcome) improved from 40.1 (SD 7.6) to 36.9 (SD 5.9) in the FMT group, whereas the scores changed from 40.1 (SD 6.9) to 41.7 (SD 6.2) in the placebo group, for a treatment benefit of 4.3 (95% CI, 3.2-5.4) (P < 0.0001). After 3-cycle intervention, symptoms of constipation, depression, and anxiety (the secondary outcome) improved significantly at week 16 in the FMT group compared with the placebo group, the majority of which were maintained at the 24-week follow-up (week 36).

INTERPRETATION: Our findings suggest that, compared with placebo, FMT treatment significantly improved motor and nonmotor symptoms in patients with PSP-RS, as well as reduced intestinal inflammation and enhanced the intestinal barrier by regulating the intestinal microbiota composition.

FUNDING: The National Natural Science Foundation of China (No. 82122022, 82171248, 81873791, and 82230084), Natural Science Foundation of Henan Province for Excellent Young Scholars (no. 202300410357), and Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project (YXKC2020033).}, } @article {pmid36968968, year = {2023}, author = {Garey, KW and Feuerstadt, P and Dubberke, ER and Guo, A and Tillotson, GS}, title = {Effect of fecal microbial transplantation on Clostridioides difficile infection: dysbiosis, metabolites and health related quality of life.}, journal = {Open forum infectious diseases}, volume = {10}, number = {3}, pages = {ofad113}, doi = {10.1093/ofid/ofad113}, pmid = {36968968}, issn = {2328-8957}, } @article {pmid36968571, year = {2023}, author = {Tucker, EC and Haylock-Jacobs, S and Rapaic, M and Dann, LM and Bryant, RV and Costello, SP}, title = {Stool donor screening within a Therapeutic Goods Administration compliant donor screening program for fecal microbiota transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {3}, pages = {172-177}, pmid = {36968571}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: This study evaluates whether a stool donor program to supply fecal microbiota transplantation (FMT) product is feasible in the Australian regulatory environment. The primary outcome was capacity to supply FMT product. The secondary outcomes were donor eligibility, retention, and output.

METHODS: Prospective observational cohort study using data collected from the stool donor and FMT production records from BiomeBank, South Australia. Participants were people who engaged with BiomeBank's donor screening and FMT manufacturing process between 01 January 2021 and 31 December 2021.

RESULTS: In total 176 people registered interest in the program, 74 of 176 (42.0%) proceeded to written questionnaire, 14 of 176 (8.0%) underwent clinical assessment, and 8 of 176 (4.5%) enrolled in the program. Two people were ineligible based on laboratory tests: both had an extended spectrum beta-lactamase producing organism in stool and one also tested positive for hepatitis B core antibody. Two donors remained eligible from 2020, resulting in 10 enrolled donors in 2021; 5 of 10 (50%) male with a median age of 36.9 years (interquartile range, 30.3-42.7 years). All donors were ineligible to donate at some time point. There were 144 stool donations processed into 1480 50 mL FMT; 413 FMT were shipped to 33 Australian hospitals for treatment, 470 for clinical trials, and 89 were destroyed prior to release from quarantine.

CONCLUSION: Recruitment into the program, retention, and maximizing the yield from a donation period was challenging. Despite this, BiomeBank was able to produce and supply FMT to Australian hospitals under the TGA-regulated Class 2 Biologicals framework.}, } @article {pmid36968567, year = {2023}, author = {Philips, CA}, title = {"Seek and find" or "search and destroy?" Identifying and retaining "healthy" stool donors for fecal microbiota transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {3}, pages = {169-171}, pmid = {36968567}, issn = {2397-9070}, } @article {pmid36965140, year = {2023}, author = {Xu, X and Li, G and Zhang, D and Zhu, H and Liu, GH and Zhang, Z}, title = {Gut Microbiota is Associated with Aging-Related Processes of a Small Mammal Species under High-Density Crowding Stress.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2205346}, doi = {10.1002/advs.202205346}, pmid = {36965140}, issn = {2198-3844}, abstract = {Humans and animals frequently encounter high-density crowding stress, which may accelerate their aging processes; however, the roles of gut microbiota in the regulation of aging-related processes under high-density crowding stress remain unclear. In the present study, it is found that high housing density remarkably increases the stress hormone (corticosterone), accelerates aging-related processes as indicated by telomere length (in brain and liver cells) and DNA damage or inflammation (as revealed by tumor necrosis factor-α and interleukin-10 levels), and reduces the lifespan of Brandt's vole (Lasiopodomys brandtii). Fecal microbiota transplantation from donor voles of habitats with different housing densities induces similar changes in aging-related processes in recipient voles. The elimination of high housing density or butyric acid administration delays the appearance of aging-related markers in the brain and liver cells of voles housed at high-density. This study suggests that gut microorganisms may play a significant role in regulating the density-dependent aging-related processes and subsequent population dynamics of animals, and can be used as potential targets for alleviating stress-related aging in humans exposed to high-density crowding stress.}, } @article {pmid36963238, year = {2023}, author = {Liu, L and Wang, H and Chen, X and Zhang, Y and Zhang, H and Xie, P}, title = {Gut microbiota and its metabolites in depression: from pathogenesis to treatment.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104527}, doi = {10.1016/j.ebiom.2023.104527}, pmid = {36963238}, issn = {2352-3964}, abstract = {Major depressive disorder is one of the most disabling mental disorders worldwide. Increasing preclinical and clinical studies have highlighted that compositional and functional (e.g., metabolite) changes in gut microbiota, known as dysbiosis, are associated with the onset and progression of depression via regulating the gut-brain axis. However, the gut microbiota and their metabolites present a double-edged sword in depression. Dysbiosis is involved in the pathogenesis of depression while, at the same time, offering a novel therapeutic target. In this review, we describe the association between dysbiosis and depression, drug-microbiota interactions in antidepressant treatment, and the potential health benefits of microbial-targeted therapeutics in depression, including dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and postbiotics. With the emergence of microbial research, we describe a new direction for future research and clinical treatment of depression.}, } @article {pmid36961604, year = {2023}, author = {Nöltner, C and Bulashevska, A and Hübscher, K and Haberstroh, H and Grimbacher, B and Proietti, M}, title = {Fecal Immunoglobulin Levels as a Modifier of the Gut Microbiome in Patients with Common Variable Immunodeficiency.}, journal = {Journal of clinical immunology}, volume = {}, number = {}, pages = {}, pmid = {36961604}, issn = {1573-2592}, abstract = {OBJECTIVE: Common variable immunodeficiency (CVID) is the most common clinically relevant entity of inborn errors of immunity. In these patients, an altered gut microbiome composition with reduced diversity has been described. We sought to investigate the fecal immunoglobulin levels and their impact on the gut microflora in patients with CVID.

METHODS: We analyzed the gut microbiome of 28 CVID patients and 42 healthy donors (HDs), including 21 healthy household controls, by sequencing the V3 and V4 regions of the bacterial 16S rRNA gene extracted from stool samples. The fecal levels of immunoglobulin A, M, and G of 27 CVID patients and 41 HDs were measured in the supernatant by ELISA and normalized for protein concentration.

RESULTS: We measured decreased IgA and increased IgG in stool samples from CVID patients compared to HDs. Decreased levels of fecal IgA and IgM were associated with reduced microbial diversity and increased dysbiosis. We identified a large number of significantly differentially abundant taxa, especially in patients with decreased IgA levels, but also in patients with decreased IgM levels compared to their counterparts.

CONCLUSIONS: CVID patients have an altered gut microbiota composition, which is most prevalent in patients with decreased fecal IgA and IgM levels. In this study, we identify fecal immunoglobulins as a potential modifier of the gut microbiome in CVID patients.}, } @article {pmid36958092, year = {2023}, author = {Xu, X and Zhuo, L and Zhang, L and Peng, H and Lyu, Y and Sun, H and Zhai, Y and Luo, D and Wang, X and Li, X and Li, L and Zhang, Y and Ma, X and Wang, Q and Li, Y}, title = {Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation.}, journal = {Psychiatry research}, volume = {323}, number = {}, pages = {115172}, doi = {10.1016/j.psychres.2023.115172}, pmid = {36958092}, issn = {1872-7123}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.}, } @article {pmid36957981, year = {2023}, author = {Stoff, R and Wolf, Y and Boursi, B}, title = {Fecal Microbiota Transplantation as a Cancer Therapeutic.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {102-108}, doi = {10.1097/PPO.0000000000000651}, pmid = {36957981}, issn = {1540-336X}, abstract = {For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.}, } @article {pmid36957977, year = {2023}, author = {Malard, F and Jenq, RR}, title = {The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {75-83}, pmid = {36957977}, issn = {1540-336X}, abstract = {Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.}, } @article {pmid36957974, year = {2023}, author = {Myojin, Y and Greten, TF}, title = {The Microbiome and Liver Cancer.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {57-60}, pmid = {36957974}, issn = {1540-336X}, abstract = {The gut microbiome and liver are anatomically and functionally connected. The impact of the gut microbiota or microbial metabolites on liver cancer progression via immune cells has been recently revealed across various preclinical models. Commensal gut microbes of liver cancer patients differ from control subjects, and their composition is affected by the etiology of the hepatocellular carcinoma. The gut microbiota represents a potential novel target for intervention as shown in patients with melanoma, but we still lack data in patients with hepatocellular carcinoma. Fecal microbiota transplantation and dietary approaches may improve immunotherapy efficacy, and a couple of clinical trials are ongoing. In liver cancer, the ongoing recognition of interactions between gut microbes and the tumor immune microenvironment provides an exciting therapeutic avenue to complement established immunotherapy.}, } @article {pmid36951547, year = {2023}, author = {Yang, Q and Wang, B and Zheng, Q and Li, H and Meng, X and Zhou, F and Zhang, L}, title = {A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2207366}, doi = {10.1002/advs.202207366}, pmid = {36951547}, issn = {2198-3844}, abstract = {Gut microbiota-derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling the tumor microenvironment and regulating key signaling pathways in cancer cells and multiple immune cells. The use of microbial metabolites in radiotherapy and chemotherapy mitigates the severe side effects from treatment and improves the efficacy of treatment. Immunotherapy combined with microbial metabolites effectively activates the immune system to kill tumors and overcomes drug resistance. Consequently, various novel strategies have been developed to modulate microbial metabolites. Manipulation of genes involved in microbial metabolism using synthetic biology approaches directly affects levels of microbial metabolites, while fecal microbial transplantation and phage strategies affect levels of microbial metabolites by altering the composition of the microbiome. However, some microbial metabolites harbor paradoxical functions depending on the context (e.g., type of cancer). Furthermore, the metabolic effects of microorganisms on certain anticancer drugs such as irinotecan and gemcitabine, render the drugs ineffective or exacerbate their adverse effects. Therefore, a personalized and comprehensive consideration of the patient's condition is required when employing microbial metabolites to treat cancer. The purpose of this review is to summarize the correlation between gut microbiota-derived metabolites and cancer, and to provide fresh ideas for future scientific research.}, } @article {pmid36951545, year = {2023}, author = {Dong, D and Su, T and Chen, W and Wang, D and Xue, Y and Lu, Q and Jiang, C and Ni, Q and Mao, E and Peng, Y}, title = {Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2192478}, doi = {10.1080/19490976.2023.2192478}, pmid = {36951545}, issn = {1949-0984}, abstract = {Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1β, as inhibition of IL-1β production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.}, } @article {pmid36949312, year = {2023}, author = {Kim, IB and Park, SC and Kim, YK}, title = {Microbiota-Gut-Brain Axis in Major Depression: A New Therapeutic Approach.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {209-224}, pmid = {36949312}, issn = {0065-2598}, abstract = {Major depression is impacted by the disruption of gut microbiota. Defects in gut microbiota can lead to microbiota-gut-brain axis dysfunction and increased vulnerability to major depression. While traditional chemotherapeutic approaches, such as antidepressant use, produce an overall partial therapeutic effect on depression, the gut microbiome has emerged as an effective target for better therapeutic outcomes. Recent representative studies on the microbiota hypothesis to explore the association between gut pathophysiology and major depression have indicated that restoring gut microbiota and microbiota-gut-brain axis could alleviate depression. We reviewed studies that supported the gut microbiota hypothesis to better understand the pathophysiology of depression; we also explored reports suggesting that gut microbiota restoration is an effective approach for improving depression. These findings indicate that gut microbiota and microbiota-gut-brain axis are appropriate new therapeutic targets for major depression.}, } @article {pmid36949306, year = {2023}, author = {Evrensel, A}, title = {Microbiome-Induced Autoimmunity and Novel Therapeutic Intervention.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {71-90}, pmid = {36949306}, issn = {0065-2598}, abstract = {Microorganisms' flora, which colonize in many parts of our body, stand out as one of the most important components for a healthy life. This microbial organization called microbiome lives in integration with the body as a single and whole organ/system. Perhaps, the human first encounters the microbial activity it carries through the immune system. This encounter and interaction are vital for the development of immune system cells that protect the body against pathogenic organisms and infections throughout life. In recent years, it has been determined that some disruptions in the host-microbiome interaction play an important role in the physiopathology of autoimmune diseases. Although the details of this interaction have not been clarified yet, the focus is on leaky gut syndrome, dysbiosis, toll-like receptor ligands, and B cell dysfunction. Nutritional regulations, prebiotics, probiotics, fecal microbiota transplantation, bacterial engineering, and vaccination are being investigated as new therapeutic approaches in the treatment of problems in these areas. This article reviews recent research in this area.}, } @article {pmid36949304, year = {2023}, author = {Shin, C and Kim, YK}, title = {Microbiota-Gut-Brain Axis: Pathophysiological Mechanism in Neuropsychiatric Disorders.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {17-37}, pmid = {36949304}, issn = {0065-2598}, abstract = {Gut microbiota influence human behavior. The immunological, metabolic, and endocrine systems are involved in bidirectional communication between the gut and the brain, which is regulated by microbes through the microbiota-derived neurochemicals and metabolites. Gut microbiota have certain effects on neurodevelopment and maturation of immunity. However, gut dysbiosis can lead to neuropsychiatric disorders. Animal research and clinical case-control studies have demonstrated that gut dysbiosis has an adverse effect on human behavior through a variety of mechanisms. Recent meta-analysis on clinical studies confirmed gut dysbiosis in several major neuropsychiatric disorders. Microbiota-targeted intervention has recently been in the spotlight and meta-analyses have confirmed its effectiveness. In this chapter, we summarize the evidence for the interactions between microbiota and brain-gut network, as well as the potential pathophysiological mechanisms involved.}, } @article {pmid36948576, year = {2023}, author = {Mishra, SP and Wang, B and Jain, S and Ding, J and Rejeski, J and Furdui, CM and Kitzman, DW and Taraphder, S and Brechot, C and Kumar, A and Yadav, H}, title = {A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-327365}, pmid = {36948576}, issn = {1468-3288}, abstract = {OBJECTIVE: Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive.

DESIGN: In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism.

RESULTS: We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis.

CONCLUSION: Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities.

TRIAL REGISTRATION NUMBER: NCT02869659 and NCT03269032.}, } @article {pmid36944780, year = {2023}, author = {Oh, M and Zhang, L}, title = {DeepGeni: deep generalized interpretable autoencoder elucidates gut microbiota for better cancer immunotherapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4599}, pmid = {36944780}, issn = {2045-2322}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; Precision Medicine ; *Microbiota ; *Melanoma/therapy ; Immunotherapy ; Fecal Microbiota Transplantation ; }, abstract = {Recent studies revealed that gut microbiota modulates the response to cancer immunotherapy and fecal microbiota transplantation has clinical benefits in melanoma patients during treatment. Understanding how microbiota affects individual responses is crucial for precision oncology. However, it is challenging to identify key microbial taxa with limited data as statistical and machine learning models often lose their generalizability. In this study, DeepGeni, a deep generalized interpretable autoencoder, is proposed to improve the generalizability and interpretability of microbiome profiles by augmenting data and by introducing interpretable links in the autoencoder. DeepGeni-based machine learning classifier outperforms state-of-the-art classifier in the microbiome-driven prediction of responsiveness of melanoma patients treated with immune checkpoint inhibitors. Moreover, the interpretable links of DeepGeni elucidate the most informative microbiota associated with cancer immunotherapy response. DeepGeni not only improves microbiome-driven prediction of immune checkpoint inhibitor responsiveness but also suggests potential microbial targets for fecal microbiota transplant or probiotics improving the outcome of cancer immunotherapy.}, } @article {pmid36943918, year = {2023}, author = {Kharofa, J and Haslam, D and Wilkinson, R and Weiss, A and Patel, S and Wang, K and Esslinger, H and Olowokure, O and Sohal, D and Wilson, G and Ahmad, S and Apewokin, S}, title = {Analysis of the fecal metagenome in long-term survivors of pancreas cancer.}, journal = {Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncr.34748}, pmid = {36943918}, issn = {1097-0142}, support = {5K08CA237735/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.

METHODS: In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.

RESULTS: All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4-14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia mucinophilia species.

CONCLUSIONS: Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia mucinophilia. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.

PLAIN LANGUAGE SUMMARY: Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%. Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system. In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls. Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia mucinophilia. These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.}, } @article {pmid36942967, year = {2023}, author = {Shi, YT and He, JM and Tong, ZA and Qian, YJ and Wang, QW and Jia, DJC and Zhu, WJ and Zhao, YX and Cai, BB and Chen, SJ and Si, MS}, title = {Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice.}, journal = {Journal of dental research}, volume = {}, number = {}, pages = {220345231158269}, doi = {10.1177/00220345231158269}, pmid = {36942967}, issn = {1544-0591}, abstract = {Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8[+] T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ[+] CD8[+] T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.}, } @article {pmid36940999, year = {2023}, author = {Jiang, S and Shen, B}, title = {[Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {37}, number = {3}, pages = {371-376}, doi = {10.7507/1002-1892.202212037}, pmid = {36940999}, issn = {1002-1892}, abstract = {OBJECTIVE: To introduce the research progress on the relationship between gut microbiota dysbiosis and osteoarthritis (OA), focus on the possible mechanism of gut microbiota dysbiosis promoting OA, and propose a new therapeutic direction.

METHODS: The domestic and foreign research literature on the relationship between gut microbiota dysbiosis and OA was reviewed. The role of the former in the occurrence and development of OA and the new ideas for the treatment of OA were summarized.

RESULTS: The gut microbiota dysbiosis promotes the development of OA mainly in three aspects. First, the gut microbiota dysbiosis destroys intestinal permeability and causes low-grade inflammation, which aggravate OA. Secondly, the gut microbiota dysbiosis promotes the development of OA through metabolic syndrome. Thirdly, the gut microbiota dysbiosis is involved in the development of OA by regulating the metabolism and transport of trace elements. Studies have shown that improving gut microbiota dysbiosis by taking probiotics and transplanting fecal microbiota can reduce systemic inflammation and regulate metabolic balance, thus treating OA.

CONCLUSION: Gut microbiota dysbiosis is closely related to the development of OA, and improving gut microbiota dysbiosis can be an important idea for OA treatment.}, } @article {pmid36938601, year = {2023}, author = {Br, VK and Sarin, SK}, title = {Acute -on- Chronic liver failure - Terminology, Mechanisms and Management.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2022.0103}, pmid = {36938601}, issn = {2287-285X}, abstract = {Acute on chronic liver failure (ACLF) is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, give an opportunity for reversal of the syndrome. Scores like the APASL ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF C-ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade HE, and in the absence of > 2 organ failure or overt sepsis as there is a high chance of failure of conservative management and high mortality to improve survival of up to 80% at five years after liver transplantation. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.}, } @article {pmid36931236, year = {2023}, author = {Walter, J and Shanahan, F}, title = {Fecal microbiota-based treatment for recurrent Clostridioides difficile infection.}, journal = {Cell}, volume = {186}, number = {6}, pages = {1087}, doi = {10.1016/j.cell.2023.02.034}, pmid = {36931236}, issn = {1097-4172}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Feces ; *Clostridium Infections/therapy ; *Microbiota ; Recurrence ; }, abstract = {Rebyota is a rectally administered fecal microbiota suspension for prevention of recurrence of Clostridioides difficile infection. The mechanism of action of Rebyota probably involves competitive exclusion of C. difficile by donor microbes with reduced toxin production; other factors may include restoration of protective taxa and modulation of the recipient's microbiome by phage, donor microbes, or metabolites.}, } @article {pmid36179888, year = {2023}, author = {Hoshino, E and Moriwaki, K and Morimoto, K and Sakai, K and Shimohata, N and Konomura, K and Urayama, KY and Suzuki, M and Shimozuma, K}, title = {Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.}, journal = {The Journal of pediatrics}, volume = {253}, number = {}, pages = {101-106.e2}, doi = {10.1016/j.jpeds.2022.09.028}, pmid = {36179888}, issn = {1097-6833}, mesh = {Infant ; Humans ; Infant, Newborn ; *Biliary Atresia/diagnosis/surgery ; Cost-Effectiveness Analysis ; Japan ; Feces ; Neonatal Screening/methods ; Bilirubin ; Cost-Benefit Analysis ; Mass Screening/methods ; }, abstract = {OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting.

STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty.

RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening.

CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.}, } @article {pmid36938236, year = {2023}, author = {Wynn, AB and Beyer, G and Richards, M and Ennis, LA}, title = {Procedure, Screening, and Cost of Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35116}, pmid = {36938236}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.}, } @article {pmid36938160, year = {2023}, author = {Spartz, EJ and Estafanos, M and Mallick, R and Gaertner, W and Vakayil, V and Jahansouz, C and Aggarwal, R and Ikramuddin, S and Khoruts, A and Harmon, JV}, title = {Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e34998}, pmid = {36938160}, issn = {2168-8184}, abstract = {Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.}, } @article {pmid36937721, year = {2023}, author = {Zhang, J and Zhu, G and Wan, L and Liang, Y and Liu, X and Yan, H and Zhang, B and Yang, G}, title = {Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1123658}, pmid = {36937721}, issn = {1664-0640}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.

METHODS: This systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.

RESULTS: The search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.

CONCLUSION: Compared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.}, } @article {pmid36937662, year = {2023}, author = {Wang, J and Liu, X and Li, Q}, title = {Interventional strategies for ischemic stroke based on the modulation of the gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1158057}, pmid = {36937662}, issn = {1662-4548}, abstract = {The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism's homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke.}, } @article {pmid36937520, year = {2023}, author = {DuPont, HL and Suescun, J and Jiang, ZD and Brown, EL and Essigmann, HT and Alexander, AS and DuPont, AW and Iqbal, T and Utay, NS and Newmark, M and Schiess, MC}, title = {Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1104759}, pmid = {36937520}, issn = {1664-2295}, abstract = {BACKGROUND AND PURPOSE: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.

METHODS: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months).

RESULTS: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group.

CONCLUSIONS: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.

CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, identifier: NCT03671785.}, } @article {pmid36936775, year = {2023}, author = {Fourati, S and Dumay, A and Roy, M and Willemetz, A and Ribeiro-Parenti, L and Mauras, A and Mayeur, C and Thomas, M and Kapel, N and Joly, F and Le Gall, M and Bado, A and Le Beyec, J}, title = {Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1023441}, pmid = {36936775}, issn = {2235-2988}, abstract = {Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.}, } @article {pmid36934020, year = {2023}, author = {Berthouzoz, E and Lazarevic, V and Zekeridou, A and Castro, M and Debove, I and Aybek, S and Schrenzel, J and Burkhard, PR and Fleury, V}, title = {Oral and intestinal dysbiosis in Parkinson's disease.}, journal = {Revue neurologique}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neurol.2022.12.010}, pmid = {36934020}, issn = {0035-3787}, abstract = {The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host. In this article, we review the dysbiosis repeatedly demonstrated in PD and how it influences PD symptoms. Dysbiosis is associated with both motor and non-motor PD symptoms. In animal models, dysbiosis only promotes symptoms in individuals genetically susceptible to Parkinson's disease, suggesting that dysbiosis is a risk factor but not a cause of Parkinson's disease. We also review how dysbiosis contributes to the pathophysiology of PD. Dysbiosis induces numerous and complex metabolic changes, resulting in increased intestinal permeability, local and systemic inflammation, production of bacterial amyloid proteins that promote α-synuclein aggregation, as well as a decrease in short-chain fatty acid-producing bacteria that have anti-inflammatory and neuroprotective potential. In addition, we review how dysbiosis decreases the efficacy of dopaminergic treatments. We then discuss the interest of dysbiosis analysis as a biomarker of Parkinson's disease. Finally, we give an overview of how interventions modulating the gut microbiota such as dietary interventions, pro-biotics, intestinal decontamination and fecal microbiota transplantation could influence the course of PD.}, } @article {pmid36931952, year = {2023}, author = {Lin, L and Zhang, K and Xiong, Q and Zhang, J and Cai, B and Huang, Z and Yang, B and Wei, B and Chen, J and Niu, Q}, title = {Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103001}, doi = {10.1016/j.jaut.2023.103001}, pmid = {36931952}, issn = {1095-9157}, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.}, } @article {pmid36930488, year = {2023}, author = {Bellucci, E and Chiereghin, F and Pacifici, F and Donadel, G and De Stefano, A and Malatesta, G and Valente, MG and Guadagni, F and Infante, M and Rovella, V and Noce, A and Tesauro, M and Di Daniele, N and Della Morte, D and Pastore, D}, title = {Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {5}, pages = {1921-1944}, doi = {10.26355/eurrev_202303_31558}, pmid = {36930488}, issn = {2284-0729}, abstract = {The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.}, } @article {pmid36928160, year = {2023}, author = {Bhatt, A and Haslam, A and Prasad, V}, title = {The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {36928160}, issn = {1432-1335}, abstract = {PURPOSE: Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment.

METHODS: Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies.

RESULTS: The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS.

CONCLUSION: Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.}, } @article {pmid36927795, year = {2023}, author = {Yi, X and Huang, C and Huang, C and Zhao, M and Lu, Q}, title = {Fecal microbiota from MRL/lpr mice exacerbates pristane-induced lupus.}, journal = {Arthritis research & therapy}, volume = {25}, number = {1}, pages = {42}, pmid = {36927795}, issn = {1478-6362}, abstract = {BACKGROUND: The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.

METHODS: We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.

RESULTS: FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.

CONCLUSION: These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.}, } @article {pmid36926604, year = {2023}, author = {Shin, YJ and Lee, DY and Kim, JY and Heo, K and Shim, JJ and Lee, JL and Kim, DH}, title = {Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice.}, journal = {Journal of ginseng research}, volume = {47}, number = {2}, pages = {255-264}, pmid = {36926604}, issn = {1226-8453}, abstract = {BACKGROUND: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice.

METHODS: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests.

RESULTS: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF[+]NeuN[+] cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased.

CONCLUSION: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.}, } @article {pmid36925044, year = {2023}, author = {Baldanzi, G and Sayols-Baixeras, S and Theorell-Haglöw, J and Dekkers, KF and Hammar, U and Nguyen, D and Lin, YT and Ahmad, S and Holm, JB and Nielsen, HB and Brunkwall, L and Benedict, C and Cedernaes, J and Koskiniemi, S and Phillipson, M and Lind, L and Sundström, J and Bergström, G and Engström, G and Smith, JG and Orho-Melander, M and Ärnlöv, J and Kennedy, B and Lindberg, E and Fall, T}, title = {Obstructive sleep apnea was associated with the human gut microbiota composition and functional potential in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS).}, journal = {Chest}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chest.2023.03.010}, pmid = {36925044}, issn = {1931-3543}, abstract = {BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.

RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?

STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.

RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.

INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.}, } @article {pmid36924566, year = {2023}, author = {Jiang, X and Liu, Z and Ma, Y and Miao, L and Zhao, K and Wang, D and Wang, M and Ruan, H and Xu, F and Zhou, Q and Xu, S}, title = {Fecal microbiota transplantation affects the recovery of AD-skin lesions and enhances gut microbiota homeostasis.}, journal = {International immunopharmacology}, volume = {118}, number = {}, pages = {110005}, doi = {10.1016/j.intimp.2023.110005}, pmid = {36924566}, issn = {1878-1705}, abstract = {BACKGROUND: Accumulating evidence has shown that gut microbiota plays a key role in the progression of atopic dermatitis (AD). Fecal microbiota transplantation (FMT), as an effective method to restore gut microbiota homeostasis, has been successfully applied for treating many inflammatory diseases. However, the therapeutic effect of FMT on AD remains unclear. The following study examined the effect and mechanism of FMT on AD-skin lesions in an AD mouse model.

METHODS: In this study, we exposed the shaved back skin of BALB/c mice to calcipotriol (MC903) to induce AD model. Mice were then treated with FMT, which was performed with gut microbiota from healthy mice. The gut microbiota of treated mice was tracked by 16S rRNA gene sequencing. Mice skin tissues were examined by histopathology and inflammatory cytokines change in serum by ELISA.

RESULTS: FMT had a faster trend on the reversion of the increases in skin epidermal layer thicknesses and suppressed some of the representative inflammatory cytokines. The gut microbial community in the natural recovery process varied significantly in the FMT group at day 7 (ANOSIM P = 0.0229, r = 0.2593). Notably, FMT had a long-lasting and beneficial impact on the gut microbial compositions of AD mice by increasing the ratio of Firmicutes to Bacteroidetes and the amount of butyric-producing bacteria (BPB), including Erysipelotrichaceae, Lactobacillaceae, and Eubacteriacea. Furthermore, the relative abundances of gut microbiota-mediated functional pathways involved in the cell growth and death, amino acid, energy, lipid, and carbohydrate metabolisms, and immune system increased after FMT treatment.

CONCLUSION: FMT modulated the gut microbiota homeostasis and affected the recovery from AD-related inflammations, suggesting that it could be used as a treatment strategy for AD patients in the clinic.}, } @article {pmid36923929, year = {2023}, author = {Shim, JA and Ryu, JH and Jo, Y and Hong, C}, title = {The role of gut microbiota in T cell immunity and immune mediated disorders.}, journal = {International journal of biological sciences}, volume = {19}, number = {4}, pages = {1178-1191}, pmid = {36923929}, issn = {1449-2288}, abstract = {Gut microbiota was only considered as a commensal organism that aids in digestion, but recent studies revealed that the microbiome play a critical role in both physiological and pathological immune system. The gut microbiome composition is altered by environmental factors such as diet and hygiene, and the alteration affects immune cells, especially T cells. Advanced genomic techniques in microbiome research defined that specific microbes regulate T cell responses and the pathogenesis of immune-mediated disorders. Here, we review features of specific microbes-T cell crosstalk and relationship between the microbes and immunopathogenesis of diseases including in cancers, autoimmune disorders and allergic inflammations. We also discuss the limitations of current experimental animal models, cutting-edge developments and current challenges to overcome in the field, and the possibility of considering gut microbiome in the development of new drug.}, } @article {pmid36923594, year = {2023}, author = {Chen, P and Wang, K and Zhuang, M and Fu, X and Liu, S and Chen, M and Lei, Y}, title = {An insight into gut microbiota and metabolites in the mice with adenomyosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1075387}, pmid = {36923594}, issn = {2235-2988}, abstract = {BACKGROUND: Adenomyosis (AM) is a benign uterine disease characterized pathologically by the invasion of endometrial tissue into the myometrium. The pathogenesis of AM is still far from clear. Although the gut microbiome and metabolomics are thought to contribute to a variety of diseases, the role of them in AM has not been revealed.

OBJECTIVE: To investigate changes in the gut microbiota and derived metabolites in AM mice.

METHOD: Female ICR mice were randomly assigned to AM and control groups, and pituitary transplantation was employed to perform AM modeling. Then, the fecal samples were obtained for microbial (16S rRNA gene sequencing) and metabolomic (liquid chromatography mass spectrometry, LC-MS) analysis.

RESULT: The results of gut microbiota analysis showed that the intestinal microbiota composition of AM mice was altered. The ratio of Firmicutes/Bacteroidetes and the relative abundance of Lactobacillus in AM group increased compared with the control group. Sixty differential expressed metabolites were identified in intestinal metabolites, mainly involved in steroid hormone biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism. Further, correlation analysis verified that L-methionine and L-cystine were negatively correlated with Bacteroides and positively correlated with Desulfovibrio. The Pregnenolone, Androsterone glucuronide, and Testosterone glucuronide were negatively correlated with Unidentified_Ruminococcaceae and Alistipes, whereas they positively correlated with Bacteroides.

CONCLUSION: AM mice have a unique gut microbiome and intestinal metabolites.}, } @article {pmid36920665, year = {2023}, author = {Costa, CJ and Cohen, MW and Goldberg, DC and Mellado, W and Willis, DE}, title = {Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {36920665}, issn = {1573-2568}, support = {NR010797/NR/NINR NIH HHS/United States ; }, abstract = {BACKGROUND: Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus.

AIMS: Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results.

MATERIALS AND METHODS: Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48 h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals.

SIGNIFICANT RESULTS: There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen.

CONCLUSIONS: NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.}, } @article {pmid36919522, year = {2023}, author = {Merenstein, D and Pot, B and Leyer, G and Ouwehand, AC and Preidis, GA and Elkins, CA and Hill, C and Lewis, ZT and Shane, AL and Zmora, N and Petrova, MI and Collado, MC and Morelli, L and Montoya, GA and Szajewska, H and Tancredi, DJ and Sanders, ME}, title = {Emerging issues in probiotic safety: 2023 perspectives.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2185034}, doi = {10.1080/19490976.2023.2185034}, pmid = {36919522}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; *Probiotics/adverse effects ; Prebiotics ; Anti-Bacterial Agents/adverse effects ; Health Status ; }, abstract = {Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.}, } @article {pmid36918627, year = {2023}, author = {Russell, MW and Muste, JC and Kuo, BL and Wu, AK and Singh, RP}, title = {Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {36918627}, issn = {1476-5454}, abstract = {Clinical trials targeting the gut microbiome to mitigate ocular disease are now on the horizon. A review of clinical data thus far is essential to determine future directions in this novel promising field. This review examines recent clinical trials that support the plausibility of a gut-eye axis, and may form the basis of novel clinical interventions. PubMed was queried for English language clinical studies examining the relationships between gut microbiota and ocular pathology. 25 studies were extracted from 828 candidate publications, which suggest that gut imbalance is associated with ocular pathology. Of these, only four interventional studies exist which suggest probiotic supplementation or fecal microbiota transplant can reduce symptoms of chalazion or uveitis. The gut-eye axis appears to hold clinical relevance, but current data is limited in sample size and design. Further investigation via longitudinal clinical trials may be warranted.}, } @article {pmid36918089, year = {2023}, author = {Kapoor, B and Gulati, M and Gupta, R and Singla, RK}, title = {Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?.}, journal = {Autoimmunity reviews}, volume = {}, number = {}, pages = {103313}, doi = {10.1016/j.autrev.2023.103313}, pmid = {36918089}, issn = {1873-0183}, abstract = {Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.}, } @article {pmid36915683, year = {2023}, author = {Aoi, W and Inoue, R and Mizushima, K and Honda, A and Björnholm, M and Takagi, T and Naito, Y}, title = {Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation.}, journal = {iScience}, volume = {26}, number = {3}, pages = {106251}, pmid = {36915683}, issn = {2589-0042}, abstract = {Habitual exercise alters the intestinal microbiota composition, which may mediate its systemic benefits. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet (HFD)-fed mice. Fecal samples from sedentary and exercise-trained mice were gavage-fed to germ-free mice. After receiving fecal samples from trained donor mice for 1 week, recipient mice had elevated levels of AMP-activated protein kinase (AMPK) and insulin growth factor-1 in skeletal muscle. In plasma, bile acid (BA) deconjugation was found to be promoted in recipients transplanted with feces from trained donor mice; free-form BAs also induced more AMPK signaling and glucose uptake than tauro-conjugated BAs. The transplantation of exercise-acclimated fecal microbiota improved glucose tolerance after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvements in mice by modifying circulating BAs. Our findings provide insights into the prevention and treatment of metabolic diseases.}, } @article {pmid36913483, year = {2023}, author = {Rehman, A and Tyree, SM and Fehlbaum, S and DunnGalvin, G and Panagos, CG and Guy, B and Patel, S and Dinan, TG and Duttaroy, AK and Duss, R and Steinert, RE}, title = {A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults.}, journal = {The Journal of nutrition}, volume = {153}, number = {1}, pages = {96-105}, doi = {10.1016/j.tjnut.2022.11.009}, pmid = {36913483}, issn = {1541-6100}, abstract = {BACKGROUND: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota.

OBJECTIVES: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites.

METHODS: Overweight and obese adults (n = 22, BMI 28-35 kg/m[2]) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance.

RESULTS: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 μM, P ≤ 0.05) and urine (-19.1 μM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05).

CONCLUSIONS: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2).}, } @article {pmid36911747, year = {2023}, author = {Wang, L and Wei, Z and Pan, F and Song, C and Peng, L and Yang, Y and Huang, F}, title = {Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1093233}, pmid = {36911747}, issn = {1664-3224}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Spondylitis, Ankylosing ; Feces ; *Gastrointestinal Microbiome ; *Microbiota ; *Colitis, Ulcerative/pathology ; }, abstract = {Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.}, } @article {pmid36910213, year = {2023}, author = {Gholam-Mostafaei, FS and Azimirad, M and Naseri, K and Nabavi-Rad, A and Asadzadeh Aghdaei, H and Shahrokh, S and Ebrahimi Daryani, N and Yadegar, A and Zali, MR}, title = {Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1147945}, pmid = {36910213}, issn = {1664-302X}, abstract = {INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD.

METHODS: A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT.

RESULTS AND DISCUSSION: Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.}, } @article {pmid36910163, year = {2023}, author = {van Lingen, EE and Baunwall, SSMD and Lieberknecht, SSC and Benech, NN and Ianiro, GG and Sokol, HH and Gasbarrini, AA and Cammarota, GG and Eriksen, MMK and van der Meulen-de Jong, AAE and Terveer, EEM and Verspaget, HHW and Vehreschild, MM and Hvas, CCL and Keller, JJJ}, title = {Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231156285}, pmid = {36910163}, issn = {1756-283X}, abstract = {BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity.

OBJECTIVES: We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD.

DESIGN: This is a multicentre cohort study conducted in five European FMT centres.

METHODS: Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death.

RESULTS: In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years).

CONCLUSION: FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.}, } @article {pmid36909725, year = {2023}, author = {Zou, B and Liu, S and Li, X and He, J and Dong, C and Ruan, M and Huang, Z and Shu, S}, title = {Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1083236}, pmid = {36909725}, issn = {2235-2988}, abstract = {BACKGROUND: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children.

METHODS: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy.

RESULTS: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029).

CONCLUSION: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.}, } @article {pmid36906253, year = {2023}, author = {Gao, T and Feng, M and Wang, Z and Cao, J and Chen, Y}, title = {Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105125}, doi = {10.1016/j.micinf.2023.105125}, pmid = {36906253}, issn = {1769-714X}, abstract = {BACKGROUND: Insufficient sleep was considered as a substantial cause of obesity. The present study further explored the mechanism whereby sleep restriction (SR)-mediated intestinal dysbiosis induced metabolic disorder and ultimately lead to obesity in mice and the improvement effect of butyrate exerting on it.

METHODS: A continuous 3 months SR mouse model with or without butyrate supplementation and fecal microbiota transplantation to explore the key role of intestinal microbiota in butyrate improving inflammatory response in inguinal white adipose tissue (iWAT) and fatty acid oxidation dysfunction in brown adipose tissue (BAT), further ameliorating SR-induced obesity.

RESULTS: SR-mediated gut microbiota dysbiosis (down-regulation in butyrate level and up-regulation in LPS level) induced intestinal permeability increase and inflammatory response in iWAT and fatty acid oxidation dysfunction in BAT, ultimately resulting in obesity. Further, we demonstrated butyrate ameliorated gut microbiota homeostasis, suppressed inflammatory response via GPR43/LPS/TLR4/MyD88/GSK-3β/β-catenin loop in iWAT and restored fatty acid oxidation function via HDAC3/PPARα/PGC-1α/UCP1/Calpain1 pathway in BAT, ultimately reversing SR-induced obesity.

CONCLUSIONS: We revealed that gut dysbiosis is a key factor for SR-induced obesity and provided a better understanding of the effects of butyrate. We further expected that reversing SR-induced obesity by improving microbiota-gut-adipose axis disorder could be a possible treatment for metabolic diseases.}, } @article {pmid36905867, year = {2023}, author = {Zhang, CE and Yu, XH and Cui, YT and Wang, HJ and Chen, X and Ma, XJ and Li, H and Su, JR and Ma, ZJ and Huang, LQ}, title = {Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {113}, number = {}, pages = {154737}, doi = {10.1016/j.phymed.2023.154737}, pmid = {36905867}, issn = {1618-095X}, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD.

PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile.

METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT).

RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism.

CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.}, } @article {pmid36904149, year = {2023}, author = {Yuan, C and Fan, J and Jiang, L and Ye, W and Chen, Z and Wu, W and Huang, Q and Qian, L}, title = {Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice.}, journal = {Nutrients}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/nu15051149}, pmid = {36904149}, issn = {2072-6643}, abstract = {Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.}, } @article {pmid36902512, year = {2023}, author = {Rodrigues, T and Rodrigues Fialho, S and Araújo, JR and Rocha, R and Moreira-Rosário, A}, title = {Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, doi = {10.3390/jcm12051725}, pmid = {36902512}, issn = {2077-0383}, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis.

METHODS: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms.

RESULTS: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I[2] = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively).

CONCLUSION: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.}, } @article {pmid36901792, year = {2023}, author = {Celiberto, F and Losurdo, G and Pricci, M and Girardi, B and Marotti, A and Di Leo, A and Ierardi, E}, title = {The State of the Art of Molecular Fecal Investigations for Helicobacter pylori (H. pylori) Antibiotic Resistances.}, journal = {International journal of molecular sciences}, volume = {24}, number = {5}, pages = {}, doi = {10.3390/ijms24054361}, pmid = {36901792}, issn = {1422-0067}, abstract = {A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.}, } @article {pmid36901656, year = {2023}, author = {Song, L}, title = {Toward Understanding Microbial Ecology to Restore a Degraded Ecosystem.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, doi = {10.3390/ijerph20054647}, pmid = {36901656}, issn = {1660-4601}, abstract = {The microbial community plays an important role in maintaining human health, addressing climate change, maintaining environmental quality, etc. High-throughput sequencing leads to the discovery and identification of more microbial community composition and function in diverse ecosystems. Microbiome therapeutics such as fecal microbiota transplantation for human health and bioaugmentation for activated sludge restoration have drawn great attention. However, microbiome therapeutics cannot secure the success of microbiome transplantation. This paper begins with a view on fecal microbiota transplantation and bioaugmentation and is followed by a parallel analysis of these two microbial therapeutic strategies. Accordingly, the microbial ecology mechanisms behind them were discussed. Finally, future research on microbiota transplantation was proposed. Successful application of both microbial therapeutics for human disease and bioremediation for contaminated environments relies on a better understanding of the microbial "entangled bank" and microbial ecology of these environments.}, } @article {pmid36899725, year = {2023}, author = {Jia, X and He, Y and Kang, Z and Chen, S and Sun, W and Wang, J and Lai, S}, title = {Comparison of Fecal Microbiota Communities between Primiparous and Multiparous Cows during Non-Pregnancy and Pregnancy.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {5}, pages = {}, doi = {10.3390/ani13050869}, pmid = {36899725}, issn = {2076-2615}, abstract = {Imbalances in the gut microbiota composition may lead to several reproductive disorders and diseases during pregnancy. This study investigates the fecal microbiome composition between primiparous and multiparous cows during non-pregnancy and pregnancy to analyze the host-microbial balance at different stages. The fecal samples obtained from six cows before their first pregnancy (BG), six cows during their first pregnancy (FT), six open cows with more than three lactations (DCNP), and six pregnant cows with more than three lactations (DCP) were subjected to 16S rRNA sequencing, and a differential analysis of the fecal microbiota composition was performed. The three most abundant phyla in fecal microbiota were Firmicutes (48.68%), Bacteroidetes (34.45%), and Euryarchaeota (15.42%). There are 11 genera with more than 1.0% abundance at the genus level. Both alpha diversity and beta diversity showed significant differences among the four groups (p < 0.05). Further, primiparous women were associated with a profound alteration of the fecal microbiota. The most representative taxa included Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG_003, Christensenellaceae_R_7_group, Ruminococcaceae UCG-005, Ruminococcaceae UCG-013, Ruminococcaceae UCG-014, Methanobrevibacter, and [Eubacterium] coprostanoligenes group, which were associated with energy metabolism and inflammation. The findings indicate that host-microbial interactions promote adaptation to pregnancy and will benefit the development of probiotics or fecal transplantation for treating dysbiosis and preventing disease development during pregnancy.}, } @article {pmid36897813, year = {2023}, author = {Clottes, P and Benech, N and Dumot, C and Jarraud, S and Vidal, H and Mechtouff, L}, title = {Gut microbiota and stroke: new avenues to improve prevention and outcome.}, journal = {European journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ene.15770}, pmid = {36897813}, issn = {1468-1331}, abstract = {Despite major recent therapeutic advances, stroke remains a leading cause of disability and death. Consequently, new therapeutic targets need to be found to improve stroke outcome. The deleterious role of gut microbiota alteration (often mentioned as "dysbiosis") on cardiovascular diseases, including stroke and its risk factors, has been increasingly recognized. Gut microbiota metabolites, such as Trimethylamine-N-Oxyde (TMAO), Short Chain Fatty Acid (SCFA), and tryptophan, play a key role. Evidence of a link between alteration of the gut microbiota and cardiovascular risk factors exists, with a possible causality link supported by several pre-clinical studies. Gut microbiota alteration also seems to be implicated at the acute phase of stroke, with observational studies showing more non-neurological complications, higher infarct size and worse clinical outcome in stroke patients with altered microbiota. Microbiota targeted strategies have been developed, including prebiotics/probiotics, fecal microbiota transplantation, SCFA and TMAO inhibitors. Research teams have been using different time windows and endpoint for their studies, with various results. Considering the available evidence, we believe that studies focusing on microbiota targeted strategies in association with conventional stroke care should be conducted. Such strategies should be considered according to three therapeutic time windows: first, at the pre-stroke (primary prevention) or post-stroke (secondary prevention) phases, to enhance the control of cardiovascular risk factors. Secondly, at the acute phase of stroke, to limit the infarct size and the systemic complications and enhance the overall clinical outcome. Thirdly, at the subacute phase of stroke, to prevent stroke recurrence and promote neurological recovery.}, } @article {pmid36897192, year = {2023}, author = {Zhang, B and Fan, X and Du, H and Zhao, M and Zhang, Z and Zhu, R and He, B and Zhang, Y and Li, X and Li, J and Gu, N}, title = {Foodborne Carbon Dot Exposure Induces Insulin Resistance through Gut Microbiota Dysbiosis and Damaged Intestinal Mucus Layer.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.3c01005}, pmid = {36897192}, issn = {1936-086X}, abstract = {Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut-liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.}, } @article {pmid36896305, year = {2023}, author = {Zhao, JW and Chang, B and Sang, LX}, title = {Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.}, journal = {World journal of gastrointestinal surgery}, volume = {15}, number = {2}, pages = {303-306}, pmid = {36896305}, issn = {1948-9366}, abstract = {Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.}, } @article {pmid36896026, year = {2023}, author = {Wang, J and Zhang, X and Li, M and Li, R and Zhao, M}, title = {Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection.}, journal = {Therapeutics and clinical risk management}, volume = {19}, number = {}, pages = {207-217}, pmid = {36896026}, issn = {1176-6336}, abstract = {BACKGROUND: Antibody-mediated rejection (AMR) is emerging as the main cause of graft loss after kidney transplantation. Our previous study revealed the gut microbiota alternation associated with AMR in kidney transplant recipients, which was predicted to affect the metabolism-related pathways.

METHODS: To further investigate the shifts in intestinal metabolic profile among kidney transplantation recipients with AMR, fecal samples from kidney transplant recipients and patients with end-stage renal disease (ESRD) were subjected to untargeted LC-MS-based metabolomics.

RESULTS: A total of 86 individuals were enrolled in this study, including 30 kidney transplantation recipients with AMR, 35 kidney transplant recipients with stable renal function (KT-SRF), and 21 participants with ESRD. Fecal metabolome in patients with ESRD and kidney transplantation recipients with KT-SRF were parallelly detected as controls. Our results demonstrated that intestinal metabolic profile of patients with AMR differed significantly from those with ESRD. A total of 172 and 25 differential metabolites were identified in the KT-AMR group, when compared with the ESRD group and the KT-SRF group, respectively, and 14 were common to the pairwise comparisons, some of which had good discriminative ability for AMR. KEGG pathway enrichment analysis demonstrated that the different metabolites between the KT-AMR and ESRD groups or between KT-AMR and KT-SRF groups were significantly enriched in 33 or 36 signaling pathways, respectively.

CONCLUSION: From the metabolic point of view, our findings may provide key clues for developing effective diagnostic biomarkers and therapeutic targets for AMR after kidney transplantation.}, } @article {pmid36894930, year = {2023}, author = {Yang, J and Wang, L and Mei, M and Guo, J and Yang, X and Liu, S}, title = {Electroacupuncture repairs intestinal barrier by upregulating CB1 through gut microbiota in DSS-induced acute colitis.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {24}, pmid = {36894930}, issn = {1749-8546}, abstract = {BACKGROUND: A few studies have reported that electroacupuncture (EA) can repair the intestinal barrier through unknown mechanisms. Cannabinoid receptor 1 (CB1) was shown to play an important role in the protection of the gut barrier in recent studies. Gut microbiota can influence the expression of CB1. In this study, we explored the effect of EA on the gut barrier in acute colitis and its mechanism.

METHODS: A dextran sulfate sodium (DSS)-induced acute colitis model, CB1 antagonist model and fecal microbiota transplantation (FMT) model were used in this study. The disease activity index (DAI) score, colon length, histological score, and inflammatory factors were detected to evaluate colonic inflammation. Methods for detecting intestinal barrier functions included the expression of tight junction proteins, intestinal permeability, and the number of goblet cells. Moreover, 16S rRNA sequencing was applied to analyze alterations in the gut microbiota. Western blotting and RT-PCR were performed to assess the levels of CB1 and autophagy-related proteins. Autophagosomes were observed by transmission electron microscopy.

RESULTS: EA reduced the DAI score, histological score, levels of inflammatory factors, and restored the colon length. Moreover, EA increased the expression of tight junction proteins and the number of goblet cells, and decreased intestinal permeability. In addition, EA remodeled the community structure of the gut microbiota, increased the expression of CB1, and enhanced the degree of autophagy. However, the therapeutic effects were reversed by CB1 antagonists. In addition, FMT in the EA group exhibited similar effects to EA and upregulated CB1.

CONCLUSIONS: We concluded that EA may protect intestinal barrier functions by increasing the expression of CB1 to enhance autophagy through gut microbiota in DSS-induced acute colitis.}, } @article {pmid36893671, year = {2023}, author = {Yang, T and Guan, Q and Shi, JS and Xu, ZH and Geng, Y}, title = {Metformin alleviates liver fibrosis in mice by enriching Lactobacillus sp. MF-1 in the gut microbiota.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1869}, number = {5}, pages = {166664}, doi = {10.1016/j.bbadis.2023.166664}, pmid = {36893671}, issn = {1879-260X}, abstract = {BACKGROUND: Liver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying mechanism.

MATERIALS AND METHODS: A liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed. We administered antibiotic treatment and performed fecal microbiota transplantation (FMT), and 16S rRNA-based microbiome analysis to evaluate the effects of the gut microbiome on metformin-treated liver fibrosis. We isolated the bacterial strain preferably enriched by metformin and assessed its antifibrotic effects.

RESULTS: Metformin treatment repaired the gut integrity of the CCl4-treated mice. It reduced the number of bacteria in colon tissues and reduced the portal vein lipopolysaccharide (LPS) levels. The FMT performed on the metformin-treated CCl4 mice alleviated their liver fibrosis and reduced their portal vein LPS levels. The markedly changed gut microbiota was screened out from the feces and named Lactobacillus sp. MF-1 (L. sp. MF-1). In the CCl4-treated mice, daily gavage of L. sp. MF-1 maintained gut integrity, inhibited bacterial translocation, and reduced liver fibrosis. Mechanistically, metformin or L. sp. MF-1 inhibited the apoptosis of intestinal epithelial cells and restored CD3[+] intestinal intraepithelial lymphocytes in the ileum and CD4[+]Foxp3[+] lamina propria lymphocytes in the colon.

CONCLUSIONS: Metformin and its enriched L. sp. MF-1 can reinforce the intestinal barrier to alleviate liver fibrosis by restoring immune function.}, } @article {pmid36892328, year = {2023}, author = {Trinh, S and Keller, L and Herpertz-Dahlmann, B and Seitz, J}, title = {[Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders].}, journal = {Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {}, number = {}, pages = {}, doi = {10.1024/1422-4917/a000928}, pmid = {36892328}, issn = {1422-4917}, abstract = {Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders Abstract: There has recently been a significant increase in interest in gut microbiota and its interaction with the brain (gut-brain axis). Not only are the findings of microbiome research interesting for basic scientists, they also offer relevant insights for clinical practice. A causal relationship between gut microbiome and various somatic diseases such as diabetes mellitus, inflammatory bowel diseases, and obesity as well as psychiatric diseases such as major depression, anxiety disorders, and eating disorders seems plausible. To study the causal relationship of intestinal bacteria with individual phenotypes, researchers apply so-called stool transplantations (fecal microbiota transplantations) in the preclinical context. For this purpose, they transfer microbiota samples from patients into laboratory animals to observe possible changes in phenotype. In the clinical context, fecal microbiota transplantation is already being used with therapeutic intentions for selected diseases, for example, recurrent infections with Clostridioides difficile or inflammatory bowel diseases; they have already become part of the official clinical guidelines for C. difficile. For many other diseases, however, including mental illnesses, the potential of using fecal transplantations for therapeutic purposes is still being explored. Previous findings suggest that the intestinal microbiome, particularly fecal microbiota transplantations, represent a promising starting point for new therapeutic approaches.}, } @article {pmid36892039, year = {2023}, author = {He, J and Yang, M and Quan, X and Wen, J and Lan, Y and Yang, H and Zhao, G and Hou, Y and Lu, J and Xu, L and Wei, L}, title = {Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {}, number = {}, pages = {}, doi = {10.1111/iju.15158}, pmid = {36892039}, issn = {1442-2042}, abstract = {OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM.

METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized.

RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites.

CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.}, } @article {pmid36891364, year = {2023}, author = {Gao, P and Liu, L and Zhang, Z and Xu, L and Wu, C and Fu, Q and Li, J and Wang, C}, title = {Abdominal catheter-induced intussusception following renal transplantation in two pediatric recipients: 2 cases report and literature review.}, journal = {Translational pediatrics}, volume = {12}, number = {2}, pages = {280-286}, pmid = {36891364}, issn = {2224-4344}, abstract = {BACKGROUND: Intussusception is a frequent abdominal emergency in the pediatric population when the proximal bowel invaginates into the distal bowel. However, catheter-induced intussusception has not previously been described in pediatric renal transplant recipients, and the risk factors need to be investigated.

CASE DESCRIPTION: We report 2 cases of post-transplant intussusception which were caused by abdominal catheters. Case 1 experienced ileocolonic intussusception 3 months after renal transplantation and presented with intermittent abdominal pain; the intussusception was successfully managed using air enema. However, this child experienced a total of 3 episodes of intussusception within 4 days, which discontinued only after removal of the peritoneal dialysis catheter. No further intussusception recurrence was observed and the patient's intermittent pain disappeared during the follow-up. Case 2 developed ileocolonic intussusception 2 days after renal transplantation and presented currant jelly stools. The intussusception was completely irreducible until the intraperitoneal drainage catheter was eliminated; the patient discharged normal feces during the following days. A search in the databases of PubMed, Web of Science, and Embase yielded 8 similar cases. Our 2 cases had a younger age at disease onset than those retrieved in the search, and abdominal catheter was revealed as a lead point. Possible leading points of the 8 previously reported cases included post-transplant lymphoproliferative disorder (PTLD), acute appendicitis, tuberculosis, lymphocele, and firm adhesions. We noted that our cases were managed successfully with nonoperative treatment, whereas the 8 reported cases underwent surgical intervention. All of the 10 cases of intussusception occurred after renal transplantation and showed that intussusception had been induced by a lead point.

CONCLUSIONS: Our 2 cases implied that abdominal catheter could be a lead point to induce intussusception, especially in pediatric recipients with abdominal disorder. This experience may be applicable to other surgeries involving indwelling abdominal catheters in children. Health practitioners should consider this pathologic lead point and avoid serious consequences when intussusception occurs.}, } @article {pmid36891304, year = {2023}, author = {Liu, X and Tang, H and Zhou, Q and Zeng, Y and Lu, B and Chen, D and Li, Y and Qian, J and Chen, M and Zhao, J and Xu, Y and Wang, M and Tan, B}, title = {Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1109281}, pmid = {36891304}, issn = {1664-3224}, abstract = {INTRODUCTION: The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.

METHODS: From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.

RESULTS: Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).

CONCLUSIONS: The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.}, } @article {pmid36890066, year = {2023}, author = {Wu, D and Zhang, C and Liu, Y and Yao, J and Yang, X and Wu, S and Du, J and Yang, X}, title = {Beyond faecal microbiota transplantation, the non-negligible role of faecal virome or bacteriophage transplantation.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2023.02.005}, pmid = {36890066}, issn = {1995-9133}, abstract = {Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic and evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining and regulating host metabolism and health. Dysbiosis has been associated with not only intestinal diseases but other diseases such as neurology disorders and cancers. Faecal microbiota transplantation (FMT) or faecal virome or bacteriophage transplantation (FVT or FBT), transfers faecal bacteria or viruses, with a focus on bacteriophage, from one healthy individual to another individual (normally unhealthy condition), and aims to restore the balanced gut microbiota and assist in subduing diseases. In this review, we summarized the applications of FMT and FVT in clinical settings, discussed the advantages and challenges of FMT and FVT currently and proposed several considerations prospectively. We further provided our understanding of why FMT and FVT have their limitations and raised the possible future development strategy of FMT and FVT.}, } @article {pmid36889449, year = {2023}, author = {Kumei, S and Ishioh, M and Nozu, T and Okumura, T}, title = {Prostaglandin I2 suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1867}, number = {5}, pages = {130344}, doi = {10.1016/j.bbagen.2023.130344}, pmid = {36889449}, issn = {1872-8006}, abstract = {In this study, we attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Since fecal 1-MNA is known for a marker of dysbiosis, we examined the composition of fecal microbiota by T-RFLP analysis. The proportion of clostridium cluster XI, XIVa and XVIII was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in IBS rats. These results suggest for the first time that PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.}, } @article {pmid36883990, year = {2023}, author = {Wu, Y and Zheng, Y and Wang, X and Tang, P and Guo, W and Ma, H and Zhang, A and Li, D and Xie, Y and Wang, CZ and Yao, H and Wan, JY and Yuan, CS}, title = {Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-23}, doi = {10.1142/S0192415X23500325}, pmid = {36883990}, issn = {1793-6853}, abstract = {Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.}, } @article {pmid36882658, year = {2023}, author = {Zhou, S and Cui, Y and Zhang, Y and Zhao, T and Cong, J}, title = {Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis.}, journal = {International journal of colorectal disease}, volume = {38}, number = {1}, pages = {62}, pmid = {36882658}, issn = {1432-1262}, abstract = {PURPOSE: Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD.

METHODS: Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model.

RESULTS: Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4 weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I[2] = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I[2] = 0) reduced Crohn's disease activity index scores 4 to 8 weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT.

CONCLUSION: FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary.

TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.}, } @article {pmid36882216, year = {2023}, author = {Körner, E and Lorentz, A}, title = {Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxad044}, pmid = {36882216}, issn = {1365-2672}, abstract = {As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score (IBS-SSS), quality of life measured by the lBS quality of life scale (IBS-QOL) and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted towards their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show, that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules or bowel cleansing. Moreover, optimal donor selection, frequency, dosage and route of delivery still need to be defined.}, } @article {pmid36756869, year = {2023}, author = {Chopra, T}, title = {A profile of the live biotherapeutic product RBX2660 and its role in preventing recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {21}, number = {3}, pages = {243-253}, doi = {10.1080/14787210.2023.2171986}, pmid = {36756869}, issn = {1744-8336}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Recurrence ; }, abstract = {INTRODUCTION: Clostridiodes difficile infection (CDI) is a life-threatening illness that has been labelled as an urgent threat by the Centers for Disease prevention (CDC).

AREAS COVERED: RBX2660, a live biotherapeutic product offers a very promising treatment option for patients with recurrent Clostridiodes difficile infection(rCDI). RBX2660 restores the healthy gut microbiome and shows clinically meaningful benefits for patients suffering from rCDI. Safety, efficacy, and tolerability of RBX2660 have been thoroughly assessed .

EXPERT OPINION: An FDA-approved, standardized, and accessible microbiota restoration product like RBX2660 would provide a new option for patients in need of treatment for rCDI by breaking the cycle of disease recurrence.}, } @article {pmid36881441, year = {2022}, author = {Daoust, L and Choi, BS and Agrinier, AL and Varin, TV and Ouellette, A and Mitchell, PL and Samson, N and Pilon, G and Levy, E and Desjardins, Y and Laplante, M and Anhê, FF and Houde, VP and Marette, A}, title = {Gnotobiotic mice housing conditions critically influence the phenotype associated with transfer of faecal microbiota in a context of obesity.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2021-326475}, pmid = {36881441}, issn = {1468-3288}, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle.

DESIGN: High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility.

RESULTS: Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites.

CONCLUSION: These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.}, } @article {pmid36880679, year = {2023}, author = {Kundu, S and Nayak, S and Rakshit, D and Singh, T and Shukla, R and Khatri, DK and Mishra, A}, title = {The microbiome-gut-brain axis in Epilepsy: Pharmacotherapeutic target from bench evidence for potential bedside applications.}, journal = {European journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ene.15767}, pmid = {36880679}, issn = {1468-1331}, abstract = {Gut-brain axis confers to the bidirectional intimation between the gut and brain and modulates gut homeostasis and central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. The preclinical and clinical report showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut-microbiota-brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased, and the level of Actinobacteria and Bacteroidetes was decreased in the epilepsy patients. The clinical and preclinical studies have also indicated that probiotics, ketogenic diet, faecal microbiota transplantation and antibiotic can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.}, } @article {pmid36880221, year = {2023}, author = {Liu, J and Liu, H and Teng, Y and Qin, N and Ren, X and Xia, X}, title = {A high-sucrose diet causes microbiota composition shift and promotes the susceptibility of mice to Salmonella Typhimurium infection.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d2fo03467k}, pmid = {36880221}, issn = {2042-650X}, abstract = {A westernized diet characterized by high fat and sugar is tightly associated with the development of metabolic diseases and inflammatory bowel disease. Although a high-fat diet has been extensively studied for its involvement in various diseases, fewer studies have examined the impact of a high-sugar diet on the development of certain diseases, particularly enteric infections. This study aimed to explore the effect of a high sucrose diet on Salmonella Typhimurium-induced infection. C57BL/6 mice received a normal diet (Control) or a high sucrose diet (HSD) for eight weeks and then were infected by Salmonella Typhimurium. The high-sugar diet profoundly altered the relative abundance of certain microbial taxa. Bacteroidetes and Verrucomicrobiota were more abundant in normal diet-fed mice than in HSD-fed mice. Moreover, short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were significantly higher in mice from the control group than the HSD group. More S. Typhimurium counts in feces and other tissues were observed in HSD-fed mice after infection. Tight junction proteins and antimicrobial peptides were significantly decreased in HSD-fed mice. Fecal microbiota transplantation (FMT) demonstrated that mice that received normal fecal microbiota had lower Salmonella Typhimurium burdens compared with mice that received HSD fecal microbiota, indicating that the altered microbial communities are associated with the severity of infection. Together, these findings suggest that the excessive intake of sucrose disturbs intestinal homeostasis and predisposes mice to Salmonella-induced infection.}, } @article {pmid36877601, year = {2023}, author = {Renteria, K and Nguyen, H and Koh, GY}, title = {The role of vitamin D in depression and anxiety disorders: a review of the literature.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/1028415X.2023.2186318}, pmid = {36877601}, issn = {1476-8305}, abstract = {BACKGROUND: Prevalence of mental health disorders continue to increase worldwide. Over the past decades, suboptimal vitamin D (VD) levels and gut dysbiosis have been associated with neurological dysfunction and psychiatric disorders.

METHODS: In this review, we examined the available literature on VD and mental health disorders, particularly depression and anxiety, in both clinical and pre-clinical studies.

RESULTS: Our extensive review failed to find a link between VD deficiency, depression, and anxiety-related behavior in preclinical animal models. However, strong evidence suggests that VD supplementation may alleviate symptoms in chronically stressed rodents, with some promising evidence from clinical studies. Further, fecal microbiota transplantations suggest a potential role of gut microbiota in neuropsychiatric disorders, although the underlying mechanisms remain to be fully elucidated. It has been postulated that serotonin, primarily produced by gut bacteria, may be a crucial factor. Hence, whether VD has the ability to impact gut microbiota and modulate serotonin synthesis warrants further investigation.

CONCLUSIONS: Taken together, literature has suggested that VD may serve as a key regulator in the gut-brain axis to modulate gut microbiota and alleviate symptoms of depression and anxiety. The inconsistent results of VD supplementation in clinical studies, particularly among VD deficient participants, suggests that current intake recommendations may need to be re-evaluated for individuals at-risk (i.e. prior to diagnosis) of developing depression and/or anxiety.}, } @article {pmid36876396, year = {2023}, author = {Ballif, A}, title = {[Not Available].}, journal = {Revue medicale suisse}, volume = {19}, number = {816}, pages = {434}, doi = {10.53738/REVMED.2023.19.816.434}, pmid = {36876396}, issn = {1660-9379}, mesh = {Humans ; *Clostridium Infections ; }, } @article {pmid36867263, year = {2023}, author = {Brenig, A and Broekaert, I and Gerner, P and Posovszky, C and Hünseler, C and Joachim, A}, title = {Microbiome analysis and fecal microbiota transfer in pediatric gastroenterology - a structured online survey in German-speaking countries.}, journal = {International journal of colorectal disease}, volume = {38}, number = {1}, pages = {59}, pmid = {36867263}, issn = {1432-1262}, mesh = {Humans ; Child ; Fecal Microbiota Transplantation ; *Gastroenterology ; Donor Selection ; *Microbiota ; Nutritional Status ; }, abstract = {PURPOSE: To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers.

METHODS: A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021.

RESULTS: A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT.

CONCLUSIONS: Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.}, } @article {pmid35668615, year = {2023}, author = {Teng, T and Sun, G and Song, X and Shi, B}, title = {The early faecal microbiota transfer alters bile acid circulation and amino acid transport of the small intestine in piglets.}, journal = {Journal of animal physiology and animal nutrition}, volume = {107}, number = {2}, pages = {564-573}, doi = {10.1111/jpn.13739}, pmid = {35668615}, issn = {1439-0396}, mesh = {Swine ; Animals ; Female ; *Fecal Microbiota Transplantation/veterinary ; *Bile Acids and Salts ; Intestine, Small ; Amino Acids ; Immunoglobulin A ; }, abstract = {The purpose of this study was to investigate the effects of faecal microbiota transfer (FMT) with lactation Min sows as faecal donor on blood immunity, small intestine amino acid transport capacity, bile acid circulation, and colon microbiota of recipient piglets. From Days 1 to 10, the recipient group (R group) was orally inoculated with a faecal suspension. The control group (Con group) was orally inoculated with sterile physiological saline. On Day 21, the results showed that the immunoglobulin A (IgA) concentration in plasma of the R group was increased (p < 0.05). The expression of 4F2hc in the jejunal mucosa and ileum mucosa of the R group was ameliorated (p < 0.05). The relative abundance of Synergistetes in the colon of the R group was increased, Proteobacteria was diminished by FMT (p < 0.05). On Day 40, the concentrations of IgA, IgG, and interleukin-2 detected in the plasma of the R group were increased (p < 0.05). FXR and fibroblast growth factor 19 gene expression was upregulated in ileum mucosa, CYP7A1 and Na[+] taurocholate cotransporter polypeptide gene expression were downregulated in the liver and organic solute transporters α/β was downregulated in colonic mucosa (p < 0.05). The relative abundance of Proteobacteria and Spirochaetes in the colon of the R group was decreased (p < 0.05). In conclusion, an early FMT with lactation Min sows as faecal donors can alter the small intestine amino acid transport capacity, bile acid circulation, and colonic microbiota of recipient piglets during lactation and after weaning.}, } @article {pmid36876136, year = {2023}, author = {Takimoto, Y and Chu, PS and Nakamoto, N and Hagihara, Y and Mikami, Y and Miyamoto, K and Morikawa, R and Teratani, T and Taniki, N and Fujimori, S and Suzuki, T and Koda, Y and Ishihara, R and Ichikawa, M and Honda, A and Kanai, T}, title = {Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis.}, journal = {iScience}, volume = {26}, number = {3}, pages = {106220}, pmid = {36876136}, issn = {2589-0042}, abstract = {The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b[+] cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.}, } @article {pmid36875849, year = {2023}, author = {Maestri, M and Santopaolo, F and Pompili, M and Gasbarrini, A and Ponziani, FR}, title = {Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1110536}, pmid = {36875849}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.}, } @article {pmid36873657, year = {2023}, author = {Matošević, M and Kos, I and Davidović, M and Ban, M and Matković, H and Jakopčić, I and Vuković Brinar, I and Szilágyi, Á and Csuka, D and Sinkovits, G and Prohászka, Z and Vrljičak, K and Lamot, L}, title = {Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1092860}, pmid = {36873657}, issn = {2296-2360}, abstract = {INTRODUCTION: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality.

CASE REPORT: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement.

CONCLUSION: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.}, } @article {pmid36864569, year = {2023}, author = {Liu, Y and Ji, X and Huang, Y and Li, Q and Ding, X and Wang, Y and Zhang, S and Wen, Q and Cui, B and Lu, X and Zhang, F}, title = {Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00365521.2023.2185476}, pmid = {36864569}, issn = {1502-7708}, abstract = {OBJECTIVES: The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC.

METHODS: This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed.

RESULTS: A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for ≥24 months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for ≥24 months with WMT monotherapy. Patients with age at UC onset of ≥60 years, mild disease severity and undergoing ≥2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of ≥60 years and ≥2 courses of WMT during the response.

CONCLUSIONS: This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.}, } @article {pmid36863483, year = {2023}, author = {Spreafico, A and Heirali, AA and Araujo, DV and Tan, TJ and Oliva, M and Schneeberger, PHH and Chen, B and Wong, MK and Stayner, LA and Hansen, AR and Saibil, SD and Wang, BX and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Xu, W and Siu, LL and Coburn, B}, title = {First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO Trial).}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.annonc.2023.02.011}, pmid = {36863483}, issn = {1569-8041}, abstract = {BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICI) in humans, and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.

PATIENTS AND METHODS: We conducted an early phase clinical trial of a cultivated, orally-delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic-4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.

RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes, however, differences in MET4-species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.

CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.}, } @article {pmid36863429, year = {2023}, author = {Lian, Z and Xu, Y and Wang, C and Chen, Y and Yuan, L and Liu, Z and Liu, Y and He, P and Cai, Z and Zhao, J}, title = {Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106714}, doi = {10.1016/j.phrs.2023.106714}, pmid = {36863429}, issn = {1096-1186}, abstract = {Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.}, } @article {pmid36863036, year = {2023}, author = {Grover, S}, title = {Continuing Medical Education Questions: March 2023.}, journal = {The American journal of gastroenterology}, volume = {118}, number = {3}, pages = {404}, doi = {10.14309/ajg.0000000000002199}, pmid = {36863036}, issn = {1572-0241}, abstract = {Article Title: Fecal Microbiota Transplantation Across the Lifespan- Balancing Efficacy, Safety, and Innovation.}, } @article {pmid36859447, year = {2023}, author = {Zhang, Y and Peng, Y and Xia, X}, title = {Autoimmune diseases and gut microbiota: a bibliometric and visual analysis from 2004 to 2022.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, pmid = {36859447}, issn = {1591-9528}, abstract = {Many studies have shown that gut microbiota is closely related to autoimmune diseases (ADs). Studies on gut microbiota and ADs have also increased significantly, but no bibliometric analysis has summarized the association between gut microbiota and ADs. This study aimed to conduct a bibliometric and visual analysis of published studies on gut microbiota and ADs. Based on the Web of Science Core Collection SCI-expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer and co-occurrence13.2 (COOC13.2) for analysis. A total of 2516 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, and the author is Mikael Knip from the USA. Hot research areas include intestinal regulation (such as dysbiosis, short chain fatty acids, and probiotics), multisystem ADs (such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease), and immune-related cells (such as T cells, and dendritic cells). Psoriasis, dysbiosis, autoimmune liver disease, and fecal microbiota transplantation may be the future research direction. Our research results can help researchers grasp the current status of ADs and gut microbiota research and find new research directions in the future.}, } @article {pmid36858183, year = {2023}, author = {Guo, P and Yang, X and Guo, X and Yang, H and Pan, J and Li, Y}, title = {Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2023.02.019}, pmid = {36858183}, issn = {1090-2139}, abstract = {Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, it is unclear whether omega-3 PUFAs improve autistic behaviors in fragile X syndrome (FXS) by altering the gut microbial composition. Here, we describe gastrointestinal problems in Fmr1 knockout (KO) mice. FMRP deficiency causes intestinal homeostasis dysfunction in mice. Fish oil (FO) as a source of omega-3 PUFAs reduces intestinal inflammation but increases the mRNA and protein levels of TJP3 in the colon of juvenile Fmr1 KO mice. Fecal microbiota transplantation from FO-fed Fmr1 KO mice increased the gut abundance of Akkermansia and Gordonibacter in recipient Fmr1 KO mice and improved gut homeostasis and autistic behaviors. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, thereby presenting a novel therapeutic approach for juvenile FXS treatment.}, } @article {pmid36730049, year = {2023}, author = {Bolia, R}, title = {Transanal Irrigation in Children With Functional Constipation: Doing It the Right Way for the Right Indication.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {76}, number = {3}, pages = {e67}, doi = {10.1097/MPG.0000000000003676}, pmid = {36730049}, issn = {1536-4801}, mesh = {Humans ; Child ; *Constipation/therapy ; Treatment Outcome ; Therapeutic Irrigation ; *Fecal Incontinence ; Anal Canal ; }, } @article {pmid36858036, year = {2023}, author = {Saleh, A and Parsa, S and Garza, M and Quigley, EMM and Abraham, BP}, title = {The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {}, doi = {10.1159/000529591}, pmid = {36858036}, issn = {1421-9875}, abstract = {BACKGROUND: Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC).

SUMMARY: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance towards optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid producing bacteria, Clostridium Cluster IV and XIVa, Odoribacter splanchnicus and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC.

KEY MESSAGES: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.}, } @article {pmid36848791, year = {2023}, author = {Tong, M and Yang, X and Liu, H and Ge, H and Huang, G and Kang, X and Yang, H and Liu, Q and Ren, P and Kuang, X and Yan, H and Shen, X and Qiao, Y and Kang, Y and Li, L and Yang, Y and Fan, W}, title = {The Trichinella spiralis-derived antigens alleviate HFD-induced obesity and inflammation in mice.}, journal = {International immunopharmacology}, volume = {117}, number = {}, pages = {109924}, doi = {10.1016/j.intimp.2023.109924}, pmid = {36848791}, issn = {1878-1705}, abstract = {Obesity, an increasingly prevalent disease worldwide, is accompanied by chronic inflammation and intestinal dysbiosis. Helminth infections have been increasingly proved to exhibit a protective role in several inflammation-associated diseases. Considering the side effects of live parasite therapy, efforts have been made to develop helminth-derived antigens as promising candidates with fewer adverse effects. This study aimed to evaluate the effect and mechanisms of TsAg (T. spiralis-derived antigens) on obesity and the associated inflammation in high-fat diet (HFD)-fed mice. C57BL/6J mice were fed a normal diet or HFD with or without TsAg treatment. The results reported that TsAg treatment alleviated body weight gain and chronic inflammation induced by HFD. In the adipose tissue, TsAg treatment prevented macrophage infiltration, reduced the expression of Th1-type (IFN-γ) and Th17-type (IL-17A) cytokines while upregulating the production of Th2-type (IL-4) cytokines. Furthermore, TsAg treatment enhanced brown adipose tissue activation and energy and lipid metabolism and reduced intestinal dysbiosis, intestinal barrier permeability and LPS/TLR4 axis inflammation. Finally, the protective role of TsAg against obesity was transmissible via the fecal microbiota transplantation approach. For the first time, our findings showed that TsAg alleviated HFD-induced obesity and inflammation via modulation of the gut microbiota and balancing the immune disorders, suggesting that TsAg might be a safer promising therapeutic strategy for obesity.}, } @article {pmid36845793, year = {2023}, author = {Erguibi, D and Kamal, K and Eddaoudi, Y and Hajri, A and Boufettal, R and Rifki El Jai, S and Chehab, F}, title = {Parietal mass caused by a fish bone: case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {2}, pages = {299-301}, pmid = {36845793}, issn = {2049-0801}, abstract = {UNLABELLED: It is a great challenge to distinguish the parietal inflammation, centered on the foreign body that pierced the digestive tract and remained in the wall before surgery, because of its atypical clinical nature. Ingestion of foreign bodies is not uncommon. Fish bones are particularly notorious culprits; however, most will pass through the gastrointestinal tract uneventfully.

PATIENTS AND METHODS: The authors report a case of a patient who presented with periumbilical abdominal pain and a computed tomography (CT) scan that revealed the presence of periumbilical fat infiltration on a foreign body admitted on the Department of Digestive Cancer Surgery and Liver Transplantation, Casablanca, Morocco. An exploratory laparotomy revealed a parietal mass centered by a fish bone.

RESULTS: Accidental ingestion of foreign bodies is common in clinical practice. However, perforation of the intestine by a foreign body is less common because the majority of foreign bodies pass without incident into the feces and only 1% of them (the sharpest and most elongated objects) will perforate the gastrointestinal tract, usually at the level of the ileum.CT, especially multidetector CT, is considered the method of choice for preoperative diagnoses of ingested foreign bodies and their complications due to its high-quality multiplanar capabilities and high resolution.Foreign body ingestion usually goes unnoticed, but the complications of this incident can be severe.

CONCLUSION: This case report highlights the fact that intestinal perforation caused by an ingested foreign body is a difficult diagnosis that should always be suspected in an attack of abdominal pain. Frequently, the clinical diagnosis is difficult, and recourse to imaging is sometimes necessary. Most of the time, the treatment is only surgical.}, } @article {pmid36844730, year = {2023}, author = {Hatahet, J and Cook, TM and Bonomo, RR and Elshareif, N and Gavini, CK and White, CR and Jesse, J and Mansuy-Aubert, V and Aubert, G}, title = {Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1105581}, pmid = {36844730}, issn = {2297-055X}, abstract = {More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.}, } @article {pmid36844713, year = {2023}, author = {Halper-Stromberg, A and Dalal, SR}, title = {The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {120-126}, pmid = {36844713}, issn = {1531-0043}, abstract = {Inflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.}, } @article {pmid36844712, year = {2023}, author = {Paine, H and Jones, F and Kinross, J}, title = {Preparing the Bowel (Microbiome) for Surgery: Surgical Bioresilience.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {138-145}, pmid = {36844712}, issn = {1531-0043}, abstract = {The preparation of the bowel for radical surgery is a corner stone of elective colorectal practice. The evidence for this intervention is of variable quality and it is often contradictory, yet there is now a global move toward the adoption of oral antibiotic therapy for the reduction of perioperative infective complications, such as surgical site infections. The gut microbiome is a critical mediator of the systemic inflammatory response to surgical injury, wound healing, and perioperative gut function. The loss of critical microbial symbiotic functions caused by bowel preparation and surgery has an adverse impact on surgical outcomes, yet the mechanisms through which this occurs are poorly defined. In this review, the evidence for bowel preparation strategies is critically appraised in the context of the gut microbiome. The impact of antibiotic therapy on the surgical gut microbiome and the importance of the intestinal "resistome" to surgical recovery is described. Data to support the augmentation of the microbiome through diet, probiotic and symbiotic approaches, as well as fecal transplantation are also appraised. Finally, we propose a novel strategy of bowel preparation defined as " surgical bioresilience " and define areas or prioritization in this emerging field. This describes the optimization of surgical intestinal homeostasis and core surgical exposome-microbiome interactions that regulate the wound immune microenvironment, the systemic inflammatory response to surgical injury, and gut function across the perioperative time course.}, } @article {pmid36844708, year = {2023}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {151-156}, pmid = {36844708}, issn = {1531-0043}, abstract = {Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.}, } @article {pmid36839510, year = {2023}, author = {Brumfield, KD and Cox, P and Geyer, J and Goepp, J}, title = {A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics-Leveraging Principles of Systems Biology.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36839510}, issn = {2076-0817}, abstract = {The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the "host" are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome "dysbiosis" and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders.}, } @article {pmid36838416, year = {2023}, author = {Eribo, OA and Naidoo, CC and Theron, G and Walzl, G and du Plessis, N and Chegou, NN}, title = {An Archetypical Model for Engrafting Bacteroides fragilis into Conventional Mice Following Reproducible Antibiotic Conditioning of the Gut Microbiota.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838416}, issn = {2076-2607}, support = {K43 TW012302/TW/FIC NIH HHS/United States ; R01 AI136894/AI/NIAID NIH HHS/United States ; }, abstract = {Bacteroides fragilis is a commonly investigated commensal bacterium for its protective role in host diseases. Here, we aimed to develop a reproducible antibiotic-based model for conditioning the gut microbiota and engrafting B. fragilis into a conventional murine host. Initially, we selected different combinations of antibiotics, including metronidazole, imipenem, and clindamycin, and investigated their efficacy in depleting the mouse Bacteroides population. We performed 16S rRNA sequencing of DNA isolated from fecal samples at different time points. The α-diversity was similar in mice treated with metronidazole (MET) and differed only at weeks 1 (p = 0.001) and 3 (p = 0.009) during metronidazole/imipenem (MI) treatment. Bacteroides compositions, during the MET and MI exposures, were similar to the pre-antibiotic exposure states. Clindamycin supplementation added to MET or MI regimens eliminated the Bacteroides population. We next repeated metronidazole/clindamycin (MC) treatment in two additional independent experiments, followed by a B. fragilis transplant. MC consistently and reproducibly eliminated the Bacteroides population. The depleted Bacteroides did not recover in a convalescence period of six weeks post-MC treatment. Finally, B. fragilis was enriched for ten days following engraftment into Bacteroides-depleted mice. Our model has potential use in gut microbiota studies that selectively investigate Bacteroides' role in diseases of interest.}, } @article {pmid36838352, year = {2023}, author = {Bainum, TB and Reveles, KR and Hall, RG and Cornell, K and Alvarez, CA}, title = {Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/microorganisms11020387}, pmid = {36838352}, issn = {2076-2607}, abstract = {Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.}, } @article {pmid36838196, year = {2023}, author = {Loublier, C and Taminiau, B and Heinen, J and Lecoq, L and Amory, H and Daube, G and Cesarini, C}, title = {Evaluation of Bacterial Composition and Viability of Equine Feces after Processing for Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/microorganisms11020231}, pmid = {36838196}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) has been used empirically for decades in equine medicine to treat intestinal dysbiosis but evidence-based information is scarce. This in vitro study aimed at assessing the effect of a commonly used pre-FMT processing method on the bacterial composition and viability of the fecal filtrate. Three samples of fresh equine manure (T0) were processed identically: the initial manure was mixed with 1 L of lukewarm water and chopped using an immersion blender to obtain a mixture (T1), which was left uncovered during 30 min (T2) and percolated through a sieve to obtain a fecal filtrate (T3). Samples were taken throughout the procedure (Tn) and immediately stored at 4 °C until processing. The 16S rDNA amplicon profiling associated with propidium monoazide treatment was performed on each sample to select live bacteria. Analyses of α and β diversity and main bacterial populations and quantitative (qPCR) analysis were performed and statistically compared (significance p < 0.05) between time points (T0-T3). No significant differences in ecological indices or mean estimated total living bacteria were found in the final fecal filtrate (T3) in regard to the original manure (T0); however, relative abundances of some minor genera (Fibrobacter, WCHB1-41_ge and Akkermansia) were significantly different in the final filtrate. In conclusion, the results support the viability of the major bacterial populations in equine feces when using the described pre-FMT protocol.}, } @article {pmid36837875, year = {2023}, author = {Katsimichas, T and Theofilis, P and Tsioufis, K and Tousoulis, D}, title = {Gut Microbiota and Coronary Artery Disease: Current Therapeutic Perspectives.}, journal = {Metabolites}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/metabo13020256}, pmid = {36837875}, issn = {2218-1989}, abstract = {The human gut microbiota is the community of microorganisms living in the human gut. This microbial ecosystem contains bacteria beneficial to their host and plays important roles in human physiology, participating in energy harvest from indigestible fiber, vitamin synthesis, and regulation of the immune system, among others. Accumulating evidence suggests a possible link between compositional and metabolic aberrations of the gut microbiota and coronary artery disease in humans. Manipulating the gut microbiota through targeted interventions is an emerging field of science, aiming at reducing the risk of disease. Among the interventions with the most promising results are probiotics, prebiotics, synbiotics, and trimethylamine N-oxide (TMAO) inhibitors. Contemporary studies of probiotics have shown an improvement of inflammation and endothelial cell function, paired with attenuated extracellular matrix remodeling and TMAO production. Lactobacilli, Bifidobacteria, and Bacteroides are some of the most well studied probiotics in experimental and clinical settings. Prebiotics may also decrease inflammation and lead to reductions in blood pressure, body weight, and hyperlipidemia. Synbiotics have been associated with an improvement in glucose homeostasis and lipid abnormalities. On the contrary, no evidence yet exists on the possible benefits of postbiotic use, while the use of antibiotics is not warranted, due to potentially deleterious effects. TMAO inhibitors such as 3,3-dimethyl-1-butanol, iodomethylcholine, and fluoromethylcholine, despite still being investigated experimentally, appear to possess anti-inflammatory, antioxidant, and anti-fibrotic properties. Finally, fecal transplantation carries conflicting evidence, mandating the need for further research. In the present review we summarize the links between the gut microbiota and coronary artery disease and elaborate on the varied therapeutic measures that are being explored in this context.}, } @article {pmid36836454, year = {2023}, author = {Stadlbauer, V}, title = {Liver-Gut-Interaction: Role of Microbiome Transplantation in the Future Treatment of Metabolic Disease.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/jpm13020220}, pmid = {36836454}, issn = {2075-4426}, abstract = {The association between shifts in gut microbiome composition and metabolic disorders is a well-recognized phenomenon. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Fecal microbiome transplantation (FMT) is a method to alter a person's microbiome composition. Although this method allowed for the establishment of proof of concept for using microbiome modulation to treat metabolic disorders, the method is not yet ready for broad application. It is a resource-intensive method that also carries some procedural risks and whose effects are not always reproducible. This review summarizes the current knowledge on FMT to treat metabolic diseases and gives an outlook on open research questions. Further research is undoubtedly required to find applications that are less resource-intensive, such as oral encapsulated formulations, and have strong and predictable results. Furthermore, a clear commitment from all stakeholders is necessary to move forward in the direction of developing live microbial agents, next-generation probiotics, and targeted dietary interventions.}, } @article {pmid36836218, year = {2023}, author = {Zhao, Y and Gong, C and Xu, J and Chen, D and Yang, B and Chen, Z and Wei, L}, title = {Research Progress of Fecal Microbiota Transplantation in Liver Diseases.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/jcm12041683}, pmid = {36836218}, issn = {2077-0383}, abstract = {A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut-liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient's gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut-liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.}, } @article {pmid36836185, year = {2023}, author = {Tiwari, P and Dwivedi, R and Bansal, M and Tripathi, M and Dada, R}, title = {Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/jcm12041650}, pmid = {36836185}, issn = {2077-0383}, abstract = {In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut-brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological disorders. Here, we have discussed the function of the GM in the GBA from the gut to the brain and the brain to the gut, the pathways associated with neurology that interacts with the GM, and the various neurological disorders associated with the GM. Furthermore, we have highlighted the recent advances and future prospects of the GBA, which may require addressing research concerns about GM and associated neurological disorders.}, } @article {pmid36835989, year = {2023}, author = {Singh, S and Pal, N and Shubham, S and Sarma, DK and Verma, V and Marotta, F and Kumar, M}, title = {Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/jcm12041454}, pmid = {36835989}, issn = {2077-0383}, abstract = {Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.}, } @article {pmid36835245, year = {2023}, author = {Haneishi, Y and Furuya, Y and Hasegawa, M and Picarelli, A and Rossi, M and Miyamoto, J}, title = {Inflammatory Bowel Diseases and Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, doi = {10.3390/ijms24043817}, pmid = {36835245}, issn = {1422-0067}, abstract = {Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract, the incidence of which has rapidly increased worldwide, especially in developing and Western countries. Recent research has suggested that genetic factors, the environment, microbiota, and immune responses are involved in the pathogenesis; however, the underlying causes of IBD are unclear. Recently, gut microbiota dysbiosis, especially a decrease in the abundance and diversity of specific genera, has been suggested as a trigger for IBD-initiating events. Improving the gut microbiota and identifying the specific bacterial species in IBD are essential for understanding the pathogenesis and treatment of IBD and autoimmune diseases. Here, we review the different aspects of the role played by gut microbiota in the pathogenesis of IBD and provide a theoretical basis for modulating gut microbiota through probiotics, fecal microbiota transplantation, and microbial metabolites.}, } @article {pmid36834904, year = {2023}, author = {Stec, A and Sikora, M and Maciejewska, M and Paralusz-Stec, K and Michalska, M and Sikorska, E and Rudnicka, L}, title = {Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, doi = {10.3390/ijms24043494}, pmid = {36834904}, issn = {1422-0067}, abstract = {Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.}, } @article {pmid36832398, year = {2023}, author = {Tain, YL and Hsu, CN}, title = {Role of the Gut Microbiota in Children with Kidney Disease.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/children10020269}, pmid = {36832398}, issn = {2227-9067}, abstract = {Disruption of the composition and structure of the gut microbiota, namely dysbiosis, dictates the pathophysiology of kidney diseases. The bidirectional kidney-gut axis is of interest in chronic kidney disease (CKD); the uremic milieu leads to intestinal dysbiosis and gut microbial metabolites and toxins implicated in the loss of kidney function and increased comorbidity burden. Considering that kidney diseases can originate in childhood or even earlier in fetal life, identification of the pathogenetic connection between gut microbiota dysbiosis and the development of pediatric renal diseases deserves more attention. This review concentrates on the pathogenic link between dysbiotic gut microbiota and pediatric renal diseases, covering CKD, kidney transplantation, hemodialysis and peritoneal dialysis, and idiopathic nephrotic syndrome. Gut microbiota-targeted therapies including dietary intervention, probiotics, prebiotics, postbiotics and fecal microbial transplantation are discussed for their potential for the treatment of pediatric renal diseases. A deeper understanding of gut microbiota in pediatric renal diseases will aid in developing innovative gut microbiota-targeted interventions for preventing or attenuating the global burden of kidney diseases.}, } @article {pmid36831641, year = {2023}, author = {Gholami, H and Chmiel, JA and Burton, JP and Maleki Vareki, S}, title = {The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy.}, journal = {Cancers}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/cancers15041300}, pmid = {36831641}, issn = {2072-6694}, support = {389137/CAPMC/CIHR/Canada ; }, abstract = {Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.}, } @article {pmid36831449, year = {2023}, author = {Knight, A and Karapetyan, L and Kirkwood, JM}, title = {Immunotherapy in Melanoma: Recent Advances and Future Directions.}, journal = {Cancers}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/cancers15041106}, pmid = {36831449}, issn = {2072-6694}, abstract = {The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment. Monoclonal antibodies directed at programmed cell death protein 1 receptor (PD-1) and its ligand (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host tumor recognition and destruction. Multiple other immunomodulatory therapeutics are under investigation to overcome resistance to ICI therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of interferon genes (STING) agonists, and fecal microbiota transplantation. In this review, we focus on the recent advances in immunotherapy for the treatment of melanoma and provide an update on novel therapies currently under investigation.}, } @article {pmid36830830, year = {2023}, author = {Campbell, C and Kandalgaonkar, MR and Golonka, RM and Yeoh, BS and Vijay-Kumar, M and Saha, P}, title = {Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/biomedicines11020294}, pmid = {36830830}, issn = {2227-9059}, abstract = {Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota-immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota-immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.}, } @article {pmid36830185, year = {2023}, author = {Helmy, YA and Taha-Abdelaziz, K and Hawwas, HAE and Ghosh, S and AlKafaas, SS and Moawad, MMM and Saied, EM and Kassem, II and Mawad, AMM}, title = {Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/antibiotics12020274}, pmid = {36830185}, issn = {2079-6382}, abstract = {Antimicrobial resistance (AMR) is one of the most important global public health problems. The imprudent use of antibiotics in humans and animals has resulted in the emergence of antibiotic-resistant bacteria. The dissemination of these strains and their resistant determinants could endanger antibiotic efficacy. Therefore, there is an urgent need to identify and develop novel strategies to combat antibiotic resistance. This review provides insights into the evolution and the mechanisms of AMR. Additionally, it discusses alternative approaches that might be used to control AMR, including probiotics, prebiotics, antimicrobial peptides, small molecules, organic acids, essential oils, bacteriophage, fecal transplants, and nanoparticles.}, } @article {pmid36830173, year = {2023}, author = {Maeda, Y and Murakami, T}, title = {Diagnosis by Microbial Culture, Breath Tests and Urinary Excretion Tests, and Treatments of Small Intestinal Bacterial Overgrowth.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/antibiotics12020263}, pmid = {36830173}, issn = {2079-6382}, abstract = {Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract and accompanies various bowel symptoms such as abdominal pain, bloating, gases, diarrhea, and so on. Clinically, SIBO is diagnosed by microbial culture in duodenum/jejunum fluid aspirates and/or the breath tests (BT) of hydrogen/methane gases after ingestion of carbohydrates such as glucose. The cultural analysis of aspirates is regarded as the golden standard for the diagnosis of SIBO; however, this is invasive and is not without risk to the patients. BT is an inexpensive and safe diagnostic test but lacks diagnostic sensitivity and specificity depending on the disease states of patients. Additionally, the urinary excretion tests are used for the SIBO diagnosis using chemically synthesized bile acid conjugates such as cholic acid (CA) conjugated with para-aminobenzoic acid (PABA-CA), ursodeoxycholic acid (UDCA) conjugated with PABA (PABA-UDCA) or conjugated with 5-aminosalicylic acid (5-ASA-UDCA). These conjugates are split by bacterial bile acid (cholylglycine) hydrolase. In the tests, the time courses of the urinary excretion rates of PABA or 5-ASA, including their metabolites, are determined as the measure of hydrolytic activity of intestinal bacteria. Although the number of clinical trials with this urinary excretion tests is small, results demonstrated the usefulness of bile acid conjugates as SIBO diagnostic substrates. PABA-UDCA disulfate, a single-pass type unabsorbable compound without the hydrolysis of conjugates, was likely to offer a simple and rapid method for the evaluation of SIBO without the use of radioisotopes or expensive special apparatus. Treatments of SIBO with antibiotics, probiotics, therapeutic diets, herbal medicines, and/or fecal microbiota transplantation are also reviewed.}, } @article {pmid36829082, year = {2023}, author = {Janczy, A and Szymanski, M and Stankiewicz, M and Kaska, L and Waleron, K and Stelmanska, E and Sledzinski, T and Mika, A}, title = {Increased Amount of Polyunsaturated Fatty Acids in the Intestinal Contents of Patients with Morbid Obesity.}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11695-023-06518-1}, pmid = {36829082}, issn = {1708-0428}, abstract = {INTRODUCTION: Obesity is associated with disturbed gut microbiota homeostasis that translates into altered intestinal and blood metabolite profiles. The long-chain fatty acid (LCFA) may be absorbed in the intestine, but until now, their composition in intestinal contents of patients with obesity has not been studied. The aim of the present study was to verify whether obesity is related to any changes in fecal LCFA content and whether intestinal LCFA content may be associated with the health status of patients with obesity.

METHODS: The fatty acid composition has been studied in stool samples obtained from 26 patients with morbid obesity and 25 lean subjects by gas chromatography-mass spectrometry. The dietary habits were assessed using the Food Frequency Questionnaire (FFQ-6).

RESULTS: Our results show for the first time that lean subjects and patients with obesity differ in their stool LCFA profiles. The levels of most n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs were significantly higher in fecal samples from people with obesity than in those from lean controls.

CONCLUSIONS: Based on the current knowledge, we have defined three hypotheses that may explain proving the cause-and-effect relationships observed differences in fecal LCFA profiles between patients with obesity and lean subjects. They may be related to alterations in fat digestion and/or LCFA absorption and diet. However, proving the cause-and-effect relationships requires further research.}, } @article {pmid36828429, year = {2023}, author = {Caggiano, G and Stasi, A and Franzin, R and Fiorentino, M and Cimmarusti, MT and Deleonardis, A and Palieri, R and Pontrelli, P and Gesualdo, L}, title = {Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives.}, journal = {Toxins}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/toxins15020115}, pmid = {36828429}, issn = {2072-6651}, abstract = {During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as cardiovascular injury (CVI), metabolic dysfunction, and inflammation. Accumulating data on the detrimental effect of uremic solutes in kidney disease supported the development of many strategies to restore eubiosis. Fecal microbiota transplantation (FMT) spread as an encouraging treatment for different dysbiosis-associated disorders. In this scenario, flourishing studies indicate that fecal transplantation could represent a novel treatment to reduce the uremic toxins accumulation. Here, we present the state-of-the-art concerning the application of FMT on kidney disease to restore eubiosis and reverse the retention of uremic toxins.}, } @article {pmid36828341, year = {2023}, author = {Liu, L and Zhang, T and Sui, Y and Li, G and Liu, L and Lu, T and Tan, H and Sun, B and Li, X and Li, L}, title = {Gut microbiota affects pancreatic fibrotic progression through immune modulation in chronic pancreatitis.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {106035}, doi = {10.1016/j.micpath.2023.106035}, pmid = {36828341}, issn = {1096-1208}, abstract = {Chronic pancreatitis (CP) is characterized by chronic progressive pancreatic inflammation, which leads to the permanent damage of exocrine and endocrine cells. CP causes irreversible morphological and functional changes, and the clinical manifestations includes abdomen pain, steatorrhea and diabetes. CP induces changes in the composition of gut microbiota that could be used as potential biomarkers for pancreatic fibrosis evaluation. Gut microbiota has emerged as key regulator of immunomodulation and gut microbiota-induced immune activation has not been explored in CP. In current study, we profiled gut microbial signatures in mouse CP model, and found that higher proportion of Streptomyces, Turicibacter, Methylobacterium, Enterococcus and Candidatus_Paenicardiniummore were positively associated with the occurrence of pancreatic fibrosis. We then identified increased CD3[+]T cells and macrophage infiltration in mouse and human CP tissues by transcriptome sequencing data from GEO database. Subsequently, we demonstrated that fecal microbiota transplantation (FMT) from CP mouse (FMT-CP) exacerbated pancreatic fibrosis by increasing CD4[+]T cells and macrophage infiltration compared to fecal samples obtained from healthy mouse donor (FMT-HC). Our study describes the link between gut microbiota dysbiosis and immune activation in pancreatic fibrotic progression, and highlights the potential therapeutic roles of FMT and CP treatment.}, } @article {pmid36825261, year = {2022}, author = {Ohkusa, T and Nishikawa, Y and Sato, N}, title = {Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {935676}, pmid = {36825261}, issn = {2296-858X}, abstract = {Intestinal bacteria coexist with humans and play a role in suppressing the invasion of pathogens, producing short-chain fatty acids, producing vitamins, and controlling the immune system. Studies have been carried out on culturable bacterial species using bacterial culture methods for many years. However, as metagenomic analysis of bacterial genes has been developed since the 1990s, it has recently revealed that many bacteria in the intestine cannot be cultured and that approximately 1,000 species and 40 trillion bacteria are present in the gut microbiota. Furthermore, the composition of the microbiota is different in each disease state compared with the healthy state, and dysbiosis has received much attention as a cause of various diseases. Regarding gastrointestinal diseases, dysbiosis has been reported to be involved in inflammatory bowel disease, irritable bowel syndrome, and non-alcoholic steatohepatitis. Recent findings have also suggested that dysbiosis is involved in colon cancer, liver cancer, pancreatic cancer, esophageal cancer, and so on. This review focuses on the relationship between the gut microbiota and gastrointestinal/hepatobiliary diseases and also discusses new therapies targeting the gut microbiota.}, } @article {pmid36825211, year = {2022}, author = {Hammond, TC and Messmer, S and Frank, JA and Lukins, D and Colwell, R and Lin, AL and Pennypacker, KR}, title = {Gut microbial dysbiosis correlates with stroke severity markers in aged rats.}, journal = {Frontiers in stroke}, volume = {1}, number = {}, pages = {}, pmid = {36825211}, issn = {2813-3056}, abstract = {BACKGROUND: An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients.

METHODS: Thirty-nine aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and 3 days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers.

RESULTS: Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p < 0.0001), Bacteroides vulgatus (7.36 fold change, p < 0.0001), and Escherichia coli (47.67 fold change, p < 0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p < 0.0001), Akkermansia muciniphila (0.78 fold change, p < 0.0001), and Lactobacillus murinus (0.40 fold change, p < 0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes.

CONCLUSION: The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.}, } @article {pmid36821954, year = {2023}, author = {Ikeda, Y and Saigo, N and Nagasaki, Y}, title = {Direct evidence for the involvement of intestinal reactive oxygen species in the progress of depression via the gut-brain axis.}, journal = {Biomaterials}, volume = {295}, number = {}, pages = {122053}, doi = {10.1016/j.biomaterials.2023.122053}, pmid = {36821954}, issn = {1878-5905}, abstract = {Depression is a serious global social problem. Various therapeutic drugs have been developed based on the monoamine hypothesis; however, treatment-resistant depression is a common clinical issue. Recently, the gut-brain axis, which is associated with the hypothesis that the intestinal environment affects the brain, has garnered significant interest, and several studies have attempted to treat brain disorders based on this axis. These attempts include fecal transplantation, probiotics and prebiotics. In this study, we focused on intestinal reactive oxygen species (ROS) because excessive ROS levels disturb the intestinal environment. To elucidate the impact of scavenging intestinal ROS on depression treatment via the gut-brain axis, a novel polymer-based antioxidant (siSMAPo[TN]), which was distributed only in the intestine and did not diffuse into the whole body after oral administration, was used. siSMAPo[TN] selectively scavenged intestinal ROS and protected the intestinal environment from damage caused by chronic restraint stress (CRS). In addition, siSMAPo[TN] suppressed physiological and behavioral depression-related symptoms in the CRS mouse model.}, } @article {pmid36819586, year = {2023}, author = {Søfteland, JM}, title = {Modulation of the intestinal bacterial flora: a viable strategy to alleviate acute mesenteric ischemia?.}, journal = {Annals of translational medicine}, volume = {11}, number = {2}, pages = {30}, pmid = {36819586}, issn = {2305-5839}, } @article {pmid36819429, year = {2023}, author = {Miró-González, ÁA and Maldonado-Chaar, SM and Zambrana-Valenzuela, R and Iglesias-Escabi, IM and Arciniegas-Medina, NJ}, title = {Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e33813}, pmid = {36819429}, issn = {2168-8184}, abstract = {The use of antibiotics has increased drastically over the last few decades. Many antibiotics can target the commensal microbiota and promote gut dysbiosis. These alterations contribute to disease onset and exacerbation. Although the etiology of inflammatory bowel disease (IBD) is mostly unknown, it involves a complex interaction among host genetics, microbiota, environmental factors, and aberrant immune responses. Studies have shown a relationship between very-early-onset inflammatory bowel disease (VEO-IBD) and microbiota alterations. The case discussed in this report endorses the current clinical evidence for this interaction. This is an anonymous record review with no identifiers involving a 23-month-old female patient who was brought to the emergency department by her parents due to persistent bloody diarrhea. Eight days before the presentation, she had experienced watery diarrhea that progressed to bloody stools. The patient had a history of acute otitis media, acute enteritis, and right-arm cutaneous abscess, for which she had received multiple antibiotic therapies. Strategies to manipulate the microbiome through diet, probiotics, antibiotics, or fecal microbiota transplantation (FMT) may be used therapeutically to modulate disease activity. A high index of clinical suspicion for VEO-IBD should be maintained for patients with a history of multiple, recurrent antibiotic use. We believe this case report will raise awareness about the issue of early anaerobic antibiotic exposure and help prevent its unnecessary use and, consequently, prevent gut microbiota dysbiosis that can lead to VEO-IBD. Also, our literature review will hopefully prompt clinicians to consider alternative therapeutic options for this patient population, such as rebuilding intestinal microbiota composition to improve VEO-IBD activity.}, } @article {pmid36818228, year = {2023}, author = {Zhu, D and Jin, X and Guo, P and Sun, Y and Zhou, L and Qing, Y and Shen, W and Ji, G}, title = {Efficacy of Faecal Microbiota Transplantation for the Treatment of Autism in Children: Meta-Analysis of Randomised Controlled Trials.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2023}, number = {}, pages = {5993628}, pmid = {36818228}, issn = {1741-427X}, abstract = {OBJECTIVE: Evidence-based research methods were applied to assess the efficacy of faecal microbiota transplantation (FMT) for the treatment of autism in children.

METHODS: We searched the Chinese Biomedical Literature, CNKI, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library databases to collect randomised controlled trials on faecal microbiota transplantation for the treatment of autism in children. The search included studies published from the creation of the respective database to 5 April 2022. Literature screening, data extraction, and quality evaluation were implemented by three investigators according to the inclusion and exclusion criteria. The meta-analysis was performed using the RevMan 5.1 software.

RESULTS: Nine studies with population-based subjects and four studies with animal-based subjects were included. Five papers were screened for the meta-analysis. The results showed that FMT markedly reduced Autism Behaviour Checklist (ABC) scores in children with autism spectrum disorder (weighted mean difference (WMD) = -14.96; 95% confidence intervals (CI), -21.68 to -8.24; P < 0.001; I [2] = 0%). FMT also reduced Childhood Autism Rating Scale (CARS) scores (WMD = -6.95; 95% CI, -8.76 to -5.14; P < 0.001; I [2] = 28.1%).

CONCLUSION: Our results indicate that FMT can benefit children with autism by reducing ABC and CARS scores, but more high-quality studies are needed to verify these results.}, } @article {pmid36816570, year = {2023}, author = {Wu, N and Li, X and Ma, H and Zhang, X and Liu, B and Wang, Y and Zheng, Q and Fan, X}, title = {The role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1108738}, pmid = {36816570}, issn = {1664-2295}, abstract = {The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain-Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.}, } @article {pmid36816181, year = {2023}, author = {Jugan, MC and KuKanich, K and Freilich, L}, title = {Clinical response in dogs with acute hemorrhagic diarrhea syndrome following randomized probiotic treatment or fecal microbiota transplant.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1050538}, pmid = {36816181}, issn = {2297-1769}, abstract = {Probiotics and fecal microbiota transplants (FMTs) are two microbiome-targeted therapies that have been investigated for use in gastrointestinal diseases associated with dysbiosis. The aim of this study was to compare the effects of an oral multi-strain probiotic and enema-administered FMTs on clinical signs and serum lipopolysaccharide in dogs with acute hemorrhagic diarrhea syndrome (AHDS). A total of 18 client-owned dogs with a diagnosis of AHDS were enrolled in a randomized, blinded study at the time of hospital admission. The dogs were randomized into two groups: the probiotic group received a daily oral probiotic (200 × 10[9] CFU/10kg q 24 h) for 14 days and a single sham enema; the FMT group received a single FMT via retention enema (10 mL/kg) and placebo oral capsule for 14 days. All dogs received concurrent standard-of-care therapy, including intravenous fluids and anti-emetics; no dogs received antimicrobials. The fecal score, disease severity scores, and serum lipopolysaccharide were measured on days 0, 3, and 14. Fourteen of eighteen enrolled dogs completed the study (n = 9 probiotics; n = 5 FMT). Lipopolysaccharide decreased on days 3 and 14 from baseline and correlated with fecal and disease severity scores. There was no difference in the duration or severity of clinical signs in dogs with AHDS following an enema-administered FMT compared to probiotic treatment. Further evaluation of serum lipopolysaccharide as a marker of disease severity and recovery is warranted.}, } @article {pmid36815880, year = {2023}, author = {Khan, RL and Khraibi, AA and Dumée, LF and Corridon, PR}, title = {From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {11}, number = {}, pages = {1091554}, pmid = {36815880}, issn = {2296-4185}, abstract = {Slaughterhouses produce large quantities of biological waste, and most of these materials are underutilized. In many published reports, the possibility of repurposing this form of waste to create biomaterials, fertilizers, biogas, and feeds has been discussed. However, the employment of particular offal wastes in xenotransplantation has yet to be extensively uncovered. Overall, viable transplantable tissues and organs are scarce, and developing bioartificial components using such discarded materials may help increase their supply. This perspective manuscript explores the viability and sustainability of readily available and easily sourced slaughterhouse waste, such as blood vessels, eyes, kidneys, and tracheas, as starting materials in xenotransplantation derived from decellularization technologies. The manuscript also examines the innovative use of animal stem cells derived from the excreta to create a bioartificial tissue/organ platform that can be translated to humans. Institutional and governmental regulatory approaches will also be outlined to support this endeavor.}, } @article {pmid36814445, year = {2023}, author = {Liu, J and Lin, H and Cao, M and Lin, T and Lin, A and Xu, W and Wang, H and He, J and Li, Y and Tang, H and Zhang, B}, title = {Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1124256}, pmid = {36814445}, issn = {2235-2988}, abstract = {BACKGROUND AND AIMS: Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease.

METHODS: We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota.

RESULTS: We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group.

CONCLUSION: We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.}, } @article {pmid36814251, year = {2023}, author = {Rashidi, A and Koyama, M and Dey, N and McLean, JS and Hill, GR}, title = {Colonization resistance is dispensable for segregation of oral and gut microbiota.}, journal = {BMC medical genomics}, volume = {16}, number = {1}, pages = {31}, pmid = {36814251}, issn = {1755-8794}, abstract = {BACKGROUND: The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria.

METHODS: We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury.

RESULTS: While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut.

CONCLUSIONS: Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance.}, } @article {pmid36813961, year = {2023}, author = {Tintelnot, J and Xu, Y and Lesker, TR and Schönlein, M and Konczalla, L and Giannou, AD and Pelczar, P and Kylies, D and Puelles, VG and Bielecka, AA and Peschka, M and Cortesi, F and Riecken, K and Jung, M and Amend, L and Bröring, TS and Trajkovic-Arsic, M and Siveke, JT and Renné, T and Zhang, D and Boeck, S and Strowig, T and Uzunoglu, FG and Güngör, C and Stein, A and Izbicki, JR and Bokemeyer, C and Sinn, M and Kimmelman, AC and Huber, S and Gagliani, N}, title = {Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {36813961}, issn = {1476-4687}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing to the high incidence of metastatic disease and limited responses to treatment[1,2]. Less than half of all patients respond to the primary treatment for PDAC, chemotherapy[3,4], and genetic alterations alone cannot explain this[5]. Diet is an environmental factor that can influence the response to therapies, but its role in PDAC is unclear. Here, using shotgun metagenomic sequencing and metabolomic screening, we show that the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. Using a combination of loss- and gain-of-function experiments, we show that the efficacy of 3-IAA and chemotherapy is licensed by neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which in combination with chemotherapy induces a downregulation of the reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 and glutathione peroxidase 7. All of this results in the accumulation of ROS and the downregulation of autophagy in cancer cells, which compromises their metabolic fitness and, ultimately, their proliferation. In humans, we observed a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. In summary, we identify a microbiota-derived metabolite that has clinical implications in the treatment of PDAC, and provide a motivation for considering nutritional interventions during the treatment of patients with cancer.}, } @article {pmid36813004, year = {2023}, author = {Guo, L and Yin, X and Liu, Q}, title = {Fecal microbiota transplantation reduces mouse mortality from Listeria monocytogenes infection.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {106036}, doi = {10.1016/j.micpath.2023.106036}, pmid = {36813004}, issn = {1096-1208}, abstract = {Listeria monocytogenes (Lm) is a food bacterium with strong pathogenicity which causes infections via the gastrointestinal tract. Mechanisms by which gut microbiota (GM) resist microbial infections have received little attention. Eight-week-old mice were orally inoculated with wild-type Lm EGD-e and fecal microbiota transplantation (FMT) employed. GM richness and diversity of infected mice changed rapidly within 24h. Firmicutes class decreased and Bacteroidetes, Tenericutes and Ruminococcaceae increased significantly. Coprococcus, Blautia and Eubacterium also increased on the 3rd day post-infection. Moreover, GM transplanted from healthy mice reduced mortality of infected mice by approximately 32%. FMT treatment decreased production of TNFα, IFN-γ, IL-1β and IL-6 relative to PBS treatment. In summary, FMT has potential as a treatment against Lm infection and may be used for bacterial resistance management. Further work is required to elucidate the key GM effector molecules.}, } @article {pmid36812497, year = {2023}, author = {Petrick, HL and Ogilvie, LM and Brunetta, HS and Robinson, A and Kirsh, AJ and Barbeau, PA and Handy, RM and Coyle-Asbil, B and Gianetto-Hill, C and Dennis, KMJH and van Loon, LJC and Chabowski, A and Schertzer, JD and Allen-Vercoe, E and Simpson, JA and Holloway, GP}, title = {Dietary nitrate and corresponding gut microbiota prevent cardiac dysfunction in obese mice.}, journal = {Diabetes}, volume = {}, number = {}, pages = {}, doi = {10.2337/db22-0575}, pmid = {36812497}, issn = {1939-327X}, abstract = {Impaired heart function can develop in diabetic individuals in the absence of coronary artery disease or hypertension, suggesting mechanisms beyond hypertension/increased afterload contribute to diabetic cardiomyopathy. Identifying therapeutic approaches that improve glycemia and prevent cardiovascular disease are clearly required for clinical management of diabetes-related comorbidities. Since intestinal bacteria are important for metabolism of nitrate, we examined if dietary nitrate and fecal microbial transplantation (FMT) from nitrate-fed mice could prevent high-fat diet (HFD)-induced cardiac abnormalities. Male C57Bl/6N mice were fed an 8-week low-fat diet (LFD), HFD, or HFD+Nitrate (4mM sodium nitrate). HFD-fed mice presented with pathological left ventricular (LV) hypertrophy, reduced stroke volume and increased end diastolic pressure, in association with increased myocardial fibrosis, glucose intolerance, adipose inflammation, serum lipids, LV mitochondrial reactive oxygen species (ROS), and gut dysbiosis. In contrast, dietary nitrate attenuated these detriments. In HFD-fed mice, FMT from HFD+Nitrate donors did not influence serum nitrate, blood pressure, adipose inflammation, or myocardial fibrosis. However, microbiota from HFD+Nitrate mice decreased serum lipids, LV ROS, and similar to FMT from LFD donors, prevented glucose intolerance and cardiac morphology changes. Therefore, the cardioprotective effects of nitrate are not dependent on reducing blood pressure, but rather mitigating gut dysbiosis, highlighting a nitrate-gut-heart axis.}, } @article {pmid36811017, year = {2023}, author = {Ralli, T and Saifi, Z and Rathee, A and Aeri, V and Kohli, K}, title = {Decoding the bidirectional relationship between gut microbiota and COVID-19.}, journal = {Heliyon}, volume = {}, number = {}, pages = {e13801}, doi = {10.1016/j.heliyon.2023.e13801}, pmid = {36811017}, issn = {2405-8440}, abstract = {From late 2019, whole world has been facing COVID-19 pandemic which is caused by SARS-CoV-2 virus. This virus primarily attacks the respiratory tract and enter host cell by binding with angiotensin 2 converting enzyme receptors present on alveoli of the lungs. Despite its binding in the lungs, many patients have reported gastrointestinal symptoms and indeed, RNA of the virus have been found in faecal sample of patients. This observation gave a clue of the involvement of gut-lung axis in this disease development and progression. From several studies reported in past two years, intestinal microbiome has shown to have bidirectional link with lungs i.e., gut dysbiosis increases the tendency of infection with COVID-19 and coronavirus can also cause perturbations in intestinal microbial composition. Thus, in this review we have tried to figure out the mechanisms by which disturbances in the gut composition can increase the susceptibility to COVID-19. Understanding these mechanisms can play a crucial role in decreasing the disease outcomes by manipulating the gut microbiome using prebiotics, probiotics, or combination of two. Even, faecal microbiota transplantation can also show better results, but intensive clinical trials need to be done first.}, } @article {pmid36810253, year = {2023}, author = {Li, Z and Zhou, E and Liu, C and Wicks, H and Yildiz, S and Razack, F and Ying, Z and Kooijman, S and Koonen, DP and Heijink, M and Kostidis, S and Giera, M and Sanders, IM and Kuijper, EJ and Smits, WK and van Dijk, KW and Rensen, PC and Wang, Y}, title = {Dietary butyrate ameliorates metabolic health associated with selective proliferation of gut Lachnospiraceae bacterium 28-4.}, journal = {JCI insight}, volume = {8}, number = {4}, pages = {}, doi = {10.1172/jci.insight.166655}, pmid = {36810253}, issn = {2379-3708}, abstract = {Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4.}, } @article {pmid36810115, year = {2023}, author = {Pan, W and Zhao, J and Wu, J and Xu, D and Meng, X and Jiang, P and Shi, H and Ge, X and Yang, X and Hu, M and Zhang, P and Tang, R and Nagaratnam, N and Zheng, K and Huang, XF and Yu, Y}, title = {Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {30}, pmid = {36810115}, issn = {2049-2618}, abstract = {BACKGROUND: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice.

RESULTS: DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment.

CONCLUSIONS: The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract.}, } @article {pmid36809182, year = {2023}, author = {Olekhnovich, EI and Ivanov, AB and Babkina, AA and Sokolov, AA and Ulyantsev, VI and Fedorov, DE and Ilina, EN}, title = {Consistent Stool Metagenomic Biomarkers Associated with the Response To Melanoma Immunotherapy.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0102322}, doi = {10.1128/msystems.01023-22}, pmid = {36809182}, issn = {2379-5077}, abstract = {The human gut microbiome plays an important role in both health and disease. Recent studies have demonstrated a strong influence of the gut microbiome composition on the efficacy of cancer immunotherapy. However, available studies have not yet succeeded in finding reliable and consistent metagenomic markers that are associated with the response to immunotherapy. Therefore, the reanalysis of the published data may improve our understanding of the association between the composition of the gut microbiome and the treatment response. In this study, we focused on melanoma-related metagenomic data, which are more abundant than are data from other tumor types. We analyzed the metagenomes of 680 stool samples from 7 studies that were published earlier. The taxonomic and functional biomarkers were selected after comparing the metagenomes of patients showing different treatment responses. The list of selected biomarkers was also validated on additional metagenomic data sets that were dedicated to the influence of fecal microbiota transplantation on the response to melanoma immunotherapy. According to our analysis, the resulting cross-study taxonomic biomarkers included three bacterial species: Faecalibacterium prausnitzii, Bifidobacterium adolescentis, and Eubacterium rectale. 101 groups of genes were identified to be functional biomarkers, including those potentially involved in the production of immune-stimulating molecules and metabolites. Moreover, we ranked the microbial species by the number of genes encoding functionally relevant biomarkers that they contained. Thus, we put together a list of potentially the most beneficial bacteria for immunotherapy success. F. prausnitzii, E. rectale, and three species of bifidobacteria stood out as the most beneficial species, even though some useful functions were also present in other bacterial species. IMPORTANCE In this study, we put together a list of potentially the most beneficial bacteria that were associated with a responsiveness to melanoma immunotherapy. Another important result of this study is the list of functional biomarkers of responsiveness to immunotherapy, which are dispersed among different bacterial species. This result possibly explains the existing irregularities between studies regarding the bacterial species that are beneficial to melanoma immunotherapy. Overall, these findings can be utilized to issue recommendations for gut microbiome correction in cancer immunotherapy, and the resulting list of biomarkers might serve as a good stepping stone for the development of a diagnostic test that is aimed at predicting patients' responses to melanoma immunotherapy.}, } @article {pmid36807754, year = {2023}, author = {Lindner, M and Radke, DI and Elke, G}, title = {[Bacterial gut microbiota-key player in sepsis].}, journal = {Medizinische Klinik, Intensivmedizin und Notfallmedizin}, volume = {}, number = {}, pages = {}, pmid = {36807754}, issn = {2193-6226}, abstract = {The gut microbiota is comprised of over 1200 different bacteria and forms a symbiotic community with the human organism, the holobiont. It plays an important role in the maintenance of homeostasis, e.g., of the immune system and essential metabolic processes. Disturbances in the balance of this reciprocal relationship are called dysbiosis and, in the field of sepsis, are associated with incidence of disease, extent of the systemic inflammatory response, severity of organ dysfunction, and mortality. In addition to providing guiding principles in the fascinating relationship between "human and microbe," this article summarizes recent findings regarding the role of the bacterial gut microbiota in sepsis, which is one a very relevant in intensive care medicine.}, } @article {pmid36806616, year = {2023}, author = {Fortman, D and Avellan, MGP and Hurd, D and Schwartz, M and Dubner, H and Hewitt, C and Berton, S and Ernst, S and Rose, A and Zarour, HWH and Davar, D}, title = {Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.}, journal = {Melanoma research}, volume = {}, number = {}, pages = {}, doi = {10.1097/CMR.0000000000000871}, pmid = {36806616}, issn = {1473-5636}, abstract = {The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.}, } @article {pmid36805882, year = {2023}, author = {Grosen, AK and Mikkelsen, S and Dahl Baunwall, SM and Dahlerup, JF and Erikstrup, LT and Hvas, CL and Erikstrup, C}, title = {Risk of Helicobacter pylori transmission by faecal microbiota transplantation via oral capsules.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2023.02.011}, pmid = {36805882}, issn = {1469-0691}, abstract = {OBJECTIVES: The aim was to determine if Helicobacter pylori is transmitted from donors to recipients by faecal microbiota transplantation (FMT) via oral capsules.

METHODS: In a cohort of faeces donors not primarily screened for H. pylori, consecutive stool samples were retrospectively analysed by the H. pylori stool antigen test (SAT). Subsequently, we analysed recipient stool samples collected before and after receiving faeces donated by H. pylori SAT-positive donors and we recorded recipient use of antibiotics and proton pump inhibitors. All stool samples were frozen upon collection and stored at -80°C until use.

RESULTS: Thirteen out of 40 faeces donors (33%, 95% confidence interval (CI) 20%-48%) were H. pylori-SAT positive. Among those positive, five donors donated faeces for 28 capsule-based FMTs performed in 26 recipients with stool samples collected before and after FMT. At a median 59 days (7-84 days) after FMT, no recipients (0%, 95% CI: 0%-11%) were H. pylori-SAT positive.

CONCLUSION: We found no occurrence of H. pylori transmission from healthy, asymptomatic donors to recipients by oral capsule-based FMT, although with a wide confidence interval.}, } @article {pmid36805186, year = {2023}, author = {Liu, N and Liu, J and Zheng, B and Zeng, X and Ye, Z and Huang, X and Liu, W and Liu, Y and Fang, Q and Chen, L and Rao, T and Ouyang, D}, title = {Gut microbiota affects sensitivity to immune-mediated isoniazid-induced liver injury.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {160}, number = {}, pages = {114400}, doi = {10.1016/j.biopha.2023.114400}, pmid = {36805186}, issn = {1950-6007}, abstract = {Isoniazid (INH) is a highly effective single and/or combined first-line anti-tuberculosis (anti-TB) therapy drug, and the hepatotoxicity greatly limits its clinical application. INH-induced liver injury (INH-DILI) is a typical immune-mediated idiosyncratic drug-induced liver injury. Existing mechanisms including genetic variations in drug metabolism and immune responses cannot fully explain the differences in susceptibility and sensitivity to INH-DILI, suggesting that other factors may be involved. Accumulating evidence indicates that the development and severity of immune-mediated liver injury is related to gut microbiota. In this study, INH exposure caused liver damage, immune disregulation and microbiota profile alteration. Depletion of gut microbiota ameliorated INH-DILI, and improved INH-DILI-associated immune disorder and inflammatory response. Moreover, hepatotoxicity of INH was ameliorated by fecal microbiota transplantation (FMT) from INH-treated mice. Notably, Bifidobacterium abundance was significantly associated with transaminase levels. In conclusion, our results suggested that the effect of gut microbiota on INH-DILI was related to immunity, and the difference in INH-DILI sensitivity was related to the structure of gut microbiota. Changes in the structure of gut microbiota by continuous exposure of INH resulted in the tolerance to liver injury, and probiotics such as Bifidobacterium might play an important role in INH-DILI and its "adaptation" phenomenon. This work provides novel evidence for elucidating the underlying mechanism of difference in individual's response to INH-DILI and potential approach for intervening anti-TB drug liver injury by modulating gut microbiota.}, } @article {pmid36805016, year = {2023}, author = {Donskey, CJ}, title = {Update on Clostridioides difficile Infection in Older Adults.}, journal = {Infectious disease clinics of North America}, volume = {37}, number = {1}, pages = {87-102}, doi = {10.1016/j.idc.2022.10.001}, pmid = {36805016}, issn = {1557-9824}, abstract = {Clostridioides difficile is a common cause of community-associated and health care-associated infections. Older adults are disproportionately affected, and long-term care facilities (LTCFs) have borne a substantial proportion of the burden of C difficile infection (CDI). Recurrences of CDI are common in older adults and have substantial adverse effects on quality of life. Appropriate diagnostic testing and management is essential for older adults in the community and in LTCFs. This review focuses on current concepts related to the epidemiology, diagnosis, and management of CDI in older adults.}, } @article {pmid36803643, year = {2023}, author = {Devolder, L and Pauwels, A and Van Remoortel, A and Falony, G and Vieira-Silva, S and Nagels, G and De Keyser, J and Raes, J and D'Hooghe, MB}, title = {Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2180316}, doi = {10.1080/19490976.2023.2180316}, pmid = {36803643}, issn = {1949-0984}, abstract = {Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.}, } @article {pmid36803386, year = {2023}, author = {Wang, Y and He, Y and Liang, Y and Liu, H and Chen, X and Kulyar, MF and Shahzad, A and Wei, K and Li, K}, title = {Fecal microbiota transplantation attenuates Escherichia coli infected outgrowth by modulating the intestinal microbiome.}, journal = {Microbial cell factories}, volume = {22}, number = {1}, pages = {30}, pmid = {36803386}, issn = {1475-2859}, abstract = {BACKGROUND: Given the crucial role of gut microbiota in animal and human health, studies on modulating the intestinal microbiome for therapeutic purposes have grasped a significant attention, of which the role of fecal microbiota transplantation (FMT) has been emphasized.

METHODS: In the current study, we evaluated the effect of FMT on gut functions in Escherichia coli (E. coli) infection by using mice model. Moreover, we also investigated the subsequently dependent variables of infection, i.e., body weight, mortality, intestinal histopathology, and the expression changes in tight junction proteins (TJPs).

RESULTS: The FMT effectively decreased weight loss and mortality to a certain extent with the restoration of intestinal villi that resulted in high histological scores for jejunum tissue damage (p < 0.05). The effect of FMT on alleviating the reduction of intestinal TJPs was also proved by immunohistochemistry analysis and mRNA expression levels. Moreover, the abundance of health-threatening bacteria, belonging to phylum Proteobacteria, family Enterobacteriaceae and Tannerellaceae, genus Escherichia-Shigella, Sphingomonas, Collinsella, etc., were significantly increased, whereas beneficial bacteria, belonging to phylum Firmicutes, family Lactobacillaceae, genus Lactobacillus were decreased in the gut of infected mice. Furthermore, we sought to investigate the association of clinical symptoms with FMT treatment with modulation in gut microbiota. According to beta diversity, the microbial community of gut microbiota results reflected the similarities between non-infected and FMT groups. The improvement of the intestinal microbiota in FMT group was characterized by the significant high level of beneficial microorganisms with the synergistic decrease of Escherichia-Shigella, Acinetobacter, and other taxa.

CONCLUSION: The findings suggest a beneficial host-microbiome correlation following fecal microbiota transplanatation for controlling gut infections and pathogens-associated diseases.}, } @article {pmid36803092, year = {2023}, author = {Wang, C and Bai, J and Chen, X and Song, J and Zhang, Y and Wang, H and Suo, H}, title = {Gut microbiome-based strategies for host health and disease.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/10408398.2023.2176464}, pmid = {36803092}, issn = {1549-7852}, abstract = {Host health and disease are influenced by changes in the abundance and structure of intestinal flora. Current strategies are focused on regulating the structure of intestinal flora to ensure host health by alleviating disease. However, these strategies are limited by multiple factors, such as host genotype, physiology (microbiome, immunity, and gender), intervention, and diet. Accordingly, we reviewed the prospects and limitations of all strategies regulating the structure and abundance of microflora, including probiotics, prebiotics, diet, fecal microbiota transplantation, antibiotics, and phages. Some new technologies that can improve these strategies are also introduced. Compared with other strategies, diets and prebiotics are associated with reduced risk and high security. Besides, phages have the potential for application in the targeted regulation of intestinal microbiota due to their high specificity. Notably, the variability in individual microflora and their metabolic response to different interventions should be considered. Future studies should use artificial intelligence combined with multi-omics to investigate the host genome and physiology based on factors, such as blood type, dietary habits, and exercise, in order to develop individualized intervention strategies to improve host health.}, } @article {pmid36800331, year = {2023}, author = {Shafique, I and Andleeb, S and Naeem, F and Ali, S and Tabassam, T and Sultan, T and Almas Abbasi, M}, title = {Cow dung putrefaction via vermicomposting using Eisenia fetida and its influence on seed sprouting and vegetative growth of Viola wittrockiana (pansy).}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0279828}, pmid = {36800331}, issn = {1932-6203}, mesh = {Animals ; Female ; Cattle ; *Viola ; *Oligochaeta ; Feces/chemistry ; Seeds ; Manure/analysis ; Soil ; }, abstract = {The current research was conducted at Vermi-tech Unit, Muzaffarabad in 2018 to evaluate the efficacy of cow dung and vermicompost on seed sprouting, seedlings, and vegetative developmental parameters of Viola x wittrokiana (pansy). In the current study, vermicompost was produced using Eisenia fetida. Physicochemical parameters of vermicompost and organic manure were recorded before each experimentation. The potting experiment was designed and comprised of eight germination mediums containing different combinations of soil, sand, cow dung, and various concentrations of vermicompost such as 10% VC, 15% VC, 20% VC, 25% VC, 30% VC, and 35% VC. Seed sprouting and seedling developmental parameters were observed for 28 days while vegetative plant growth parameters were recorded after 10 weeks of transplantation in various vermicompost amended germination media. Pre and post-physicochemical analysis of germination media were also recorded to check their quality and permanency. The current findings showed that 30% VC germination media was an effective dose for early seed germination initiation and all seed germination parameters. However, the significant vegetative plant growth and flowering parameters of pansy occurred at 35% VC. Findings revealed that vermicompost not only enhanced the seed germination and growth of pansy but also improved soil health. These results indicate that vermicompost can be exploited as a potent bio-fertilizer for ornamental plant production.}, } @article {pmid36799251, year = {2023}, author = {Rector, A and Bloemen, M and Thijssen, M and Delang, L and Raymenants, J and Thibaut, J and Pussig, B and Fondu, L and Aertgeerts, B and Van Ranst, M and Van Geet, C and Arnout, J and Wollants, E}, title = {Monitoring of SARS-CoV-2 concentration and circulation of variants of concern in wastewater of Leuven, Belgium.}, journal = {Journal of medical virology}, volume = {}, number = {}, pages = {}, doi = {10.1002/jmv.28587}, pmid = {36799251}, issn = {1096-9071}, abstract = {BACKGROUND: Wastewater surveillance plays an important role in the management of the COVID-19 pandemic all over the world. Using different wastewater collection points in Leuven, we wanted to investigate the use of wastewater surveillance as an early warning system for an uprise of infections, and as a tool to follow the circulation of specific variants of concern (VOC) in particular geographic areas.

METHODS: Wastewater samples were collected from local neighborhood sewers and from a large regional wastewater treatment plant (WWTP) in the area of Leuven, Belgium. After virus concentration, SARS-CoV-2 RNA was quantified by RT-qPCR and normalized with the human fecal indicator pepper mild mottle virus (PMMoV). A combination of multiplex RT-qPCR assays was used to detect signature mutations of circulating VOCs. Fecal virus shedding of SARS-CoV-2 variants was measured in feces samples of hospitalized patients.

RESULTS: In two residential sampling sites, a rise in wastewater SARS-CoV-2 concentration preceded peaks in positive cases. In the WWTP, viral load peaks were seen concomitant with the consecutive waves of positive cases caused by the original Wuhan SARS-CoV-2 strain and subsequent VOCs. During the Omicron BA.1 wave, the wastewater viral load increased to a lesser degree, even after normalization of SARS-CoV-2 concentration using PMMoV. This might be attributable to a lower level of fecal excretion of this variant. Circulation of SARS-CoV-2 VOCs Alpha, Delta, Omicron BA1/BA.2 and BA.4/BA.5 could be detected based on the presence of specific key mutations. The shift in variants was noticeable in the wastewater, with key mutations of two different variants being present simultaneously during the transition period.

CONCLUSIONS: Wastewater-based surveillance is a sensitive tool to monitor SARS-CoV-2 circulation levels and VOCs in larger regions. In times of reduced test capacity this can prove to be highly valuable. Differences in excretion levels of various SARS-CoV-2 variants should however be taken into account when using wastewater surveillance to monitor SARS-CoV-2 circulation levels in the population. This article is protected by copyright. All rights reserved.}, } @article {pmid36798129, year = {2023}, author = {Yuan, H and Gui, R and Wang, Z and Fang, F and Zhao, H}, title = {Gut microbiota: A novel and potential target for radioimmunotherapy in colorectal cancer.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1128774}, pmid = {36798129}, issn = {1664-3224}, abstract = {Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate, and is a major burden on human health worldwide. Gut microbiota regulate human immunity and metabolism through producing numerous metabolites, which act as signaling molecules and substrates for metabolic reactions in various biological processes. The importance of host-gut microbiota interactions in immunometabolic mechanisms in CRC is increasingly recognized, and interest in modulating the microbiota to improve patient's response to therapy has been raising. However, the specific mechanisms by which gut microbiota interact with immunotherapy and radiotherapy remain incongruent. Here we review recent advances and discuss the feasibility of gut microbiota as a regulatory target to enhance the immunogenicity of CRC, improve the radiosensitivity of colorectal tumor cells and ameliorate complications such as radiotoxicity. Currently, great breakthroughs in the treatment of non-small cell lung cancer and others have been achieved by radioimmunotherapy, but radioimmunotherapy alone has not been effective in CRC patients. By summarizing the recent preclinical and clinical evidence and considering regulatory roles played by microflora in the gut, such as anti-tumor immunity, we discuss the potential of targeting gut microbiota to enhance the efficacy of radioimmunotherapy in CRC and expect this review can provide references and fresh ideas for the clinical application of this novel strategy.}, } @article {pmid36796501, year = {2023}, author = {Wang, R and Jiang, C and Wu, Z and Wang, Z and Peng, Y and Li, Z and Zhang, Z and Lin, H and Chen, Z}, title = {Fecal microbiota transplantation revealed a pain-related gut microbiota community in ovariectomized mice.}, journal = {The journal of pain}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpain.2023.02.003}, pmid = {36796501}, issn = {1528-8447}, abstract = {Higher sensitivity to pain is a common clinical symptom in postmenopausal females. The gut microbiota (GM) has recently been identified as participating in various pathophysiological processes and may change during menopause and contribute to multiple postmenopausal symptoms. Here, we investigated the possible correlation between GM alteration and allodynia in ovariectomized (OVX) mice. Results showed that OVX mice exhibited allodynia from 7 weeks after surgery compared with sham-operated (SHAM) mice by comparing pain-related behaviors. Fecal microbiota transplantation (FMT) from OVX mice induced allodynia in normal mice while FMT from SHAM mice alleviated allodynia in OVX mice. Microbiome 16S rRNA sequencing and linear discriminant analysis revealed alteration of the GM after OVX. Furthermore, Spearman's correlation analysis showed associations between pain-related behaviors and genera, and further verification identified the possible pain-related genera complex. Our findings provide new insights into the underlying mechanisms of postmenopausal allodynia, and suggest pain-related microbiota community as a promising therapeutic target. PERSPECTIVE: This article provided the evidence of gut microbiota playing essential roles in postmenopausal allodynia. This work intended to offer a guidance for further mechanism investigation into gut-brain axis and probiotics screening for postmenopausal chronic pain.}, } @article {pmid36794804, year = {2023}, author = {Kurt, F and Leventhal, GE and Spalinger, MR and Anthamatten, L and Rogalla von Bieberstein, P and Menzi, C and Reichlin, M and Meola, M and Rosenthal, F and Rogler, G and Lacroix, C and de Wouters, T}, title = {Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP).}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2177486}, doi = {10.1080/19490976.2023.2177486}, pmid = {36794804}, issn = {1949-0984}, abstract = {The success of fecal microbiota transplants (FMT) has provided the necessary proof-of-concept for microbiome therapeutics. Yet, feces-based therapies have many associated risks and uncertainties, and hence defined microbial consortia that modify the microbiome in a targeted manner have emerged as a promising safer alternative to FMT. The development of such live biotherapeutic products has important challenges, including the selection of appropriate strains and the controlled production of the consortia at scale. Here, we report on an ecology- and biotechnology-based approach to microbial consortium construction that overcomes these issues. We selected nine strains that form a consortium to emulate the central metabolic pathways of carbohydrate fermentation in the healthy human gut microbiota. Continuous co-culturing of the bacteria produces a stable and reproducible consortium whose growth and metabolic activity are distinct from an equivalent mix of individually cultured strains. Further, we showed that our function-based consortium is as effective as FMT in counteracting dysbiosis in a dextran sodium sulfate mouse model of acute colitis, while an equivalent mix of strains failed to match FMT. Finally, we showed robustness and general applicability of our approach by designing and producing additional stable consortia of controlled composition. We propose that combining a bottom-up functional design with continuous co-cultivation is a powerful strategy to produce robust functionally designed synthetic consortia for therapeutic use.}, } @article {pmid36794690, year = {2023}, author = {Carnero, EA and Bock, CP and Liu, Y and Corbin, KD and Wohlers-Kariesch, E and Ruud, K and Moon, J and Marcus, A and Krajmalnik-Brown, R and Muraviev, A and Vodopyanov, KL and Smith, SR}, title = {Measurement of 24-hour Continuous Human CH4 Release in a Whole Room Indirect Calorimeter.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {}, number = {}, pages = {}, doi = {10.1152/japplphysiol.00705.2022}, pmid = {36794690}, issn = {1522-1601}, abstract = {UNLABELLED: We describe the technology and validation of a new whole room indirect calorimeter (WRIC) methodology to quantify volume of methane (VCH4) released from the human body over 24h concurrently with the assessment of energy expenditure and substrate utilization. The new system extends the assessment of energy metabolism by adding CH4, a downstream product of microbiome fermentation that could contribute to energy balance.

METHODS: Our new system consists of an established WRIC combined with the addition of off-axis integrated-cavity output spectroscopy (OA-ICOS) to measure CH4 concentration ([CH4]). Development, validation, and reliability of the system included environmental experiments to measure the stability of the atmospheric [CH4], infusing CH4 into the WRIC and human cross-validation studies comparing [CH4] quantified by OA-ICOS and mid-infrared dual-comb spectroscopy (MIR DCS).

RESULTS: Our infusion data indicated that the system measured 24h [CH4] and VCH4 with high sensitivity, reliability and validity. Cross-validation studies showed good agreement between OA-ICOS and MIR DCS technologies (r=0.979, P<0.0001). Human data revealed 24h VCH4 was highly variable between subjects and within/between days. Finally, our method to quantify VCH4 released by breath or colon suggested that over 50% of the CH4 was eliminated through the breath.

CONCLUSIONS: The method allows, for the first time, measurement of 24h VCH4 (in kcal) and therefore the measurement of the proportion of human energy intake fermented to CH4 by the gut microbiome and released via breath or from the intestine; also, it allows us to track the effects of dietary, probiotic, bacterial and fecal microbiota transplantation on VCH4.}, } @article {pmid36794370, year = {2023}, author = {van Lier, YF and Vos, J and Blom, B and Hazenberg, MD}, title = {Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2178805}, doi = {10.1080/19490976.2023.2178805}, pmid = {36794370}, issn = {1949-0984}, abstract = {Many patients with hematological malignancies, such as acute myeloid leukemia, receive an allogeneic hematopoietic cell transplantation (HCT) to cure their underlying condition. Allogeneic HCT recipients are exposed to various elements during the pre-, peri- and post-transplant period that can disrupt intestinal microbiota, including chemo- and radiotherapy, antibiotics, and dietary changes. The dysbiotic post-HCT microbiome is characterized by low fecal microbial diversity, loss of anaerobic commensals, and intestinal domination, particularly by Enterococcus species, and is associated with poor transplant outcomes. Graft-versus-host disease (GvHD) is a frequent complication of allogeneic HCT caused by immunologic disparity between donor and host cells and results in tissue damage and inflammation. Microbiota injury is particularly pronounced in allogeneic HCT recipients who go on to develop GvHD. At present, manipulation of the microbiome for example, via dietary interventions, antibiotic stewardship, prebiotics, probiotics, or fecal microbiota transplantation, is widely being explored to prevent or treat gastrointestinal GvHD. This review discusses current insights into the role of the microbiome in GvHD pathogenesis and summarizes interventions to prevent and treat microbiota injury.}, } @article {pmid36793054, year = {2023}, author = {Li, J and Huang, H and Fan, R and Hua, Y and Ma, W}, title = {Lipidomic analysis of brain and hippocampus from mice fed with high-fat diet and treated with fecal microbiota transplantation.}, journal = {Nutrition & metabolism}, volume = {20}, number = {1}, pages = {12}, pmid = {36793054}, issn = {1743-7075}, abstract = {BACKGROUND: Dietary fat intake affects brain composition and function. Different types of dietary fatty acids alter species and abundance of brain lipids in mice. The aim of this study is to explore whether the changes are effective through gut microbiota.

METHODS: In our study, 8-week-old male C57BL/6 mice were randomly divided into 7 groups and fed with high-fat diet (HFD) with different fatty acid compositions, control (CON) group, long-chain saturated fatty acid (LCSFA) group, medium-chain saturated fatty acid (MCSFA) group, n-3 polyunsaturated fatty acid (n-3 PUFA) group, n-6 polyunsaturated fatty acid (n-6 PUFA) group, monounsaturated fatty acid (MUFA) group and trans fatty acid (TFA) group. Then, the fecal microbiota transplant (FMT) was performed in other pseudo germ-free mice after antibiotic treatment. The experimental groups were orally perfused with gut microbiota that induced by HFD with different types of dietary fatty acids. The mice were fed with regular fodder before and after FMT. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to analysis the composition of fatty acids in the brain of HFD-fed mice and hippocampus of mice treated with FMT which was collected from HFD-fed mice.

RESULTS: The content of acyl-carnitines (AcCa) increased and lysophosphatidylgylcerol (LPG) decreased in all kinds of HFD groups. phosphatidic acids (PA), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents were significantly increased in the n-6 PUFA-fed HFD group. The HFD elevated the saturation of brain fatty acyl (FA). Lysophosphatidylcholine (LPC), lysodi-methylphosphatidylethanolamine (LdMePE), monolysocardiolipin (MLCL), dihexosylceramides (Hex2Cer), and wax ester (WE) significantly increased after LCSFA-fed FMT. MLCL reduced and cardiolipin (CL) raised significantly after n-3 PUFA-fed FMT.

CONCLUSIONS: The study revealed, HFD and FMT in mice had certain effects on the content and composition of fatty acids in the brain, especially on glycerol phospholipid (GP). The change of AcCa content in FA was a good indicator of dietary fatty acid intake. By altering the fecal microbiota, dietary fatty acids might affect brain lipids.}, } @article {pmid36791303, year = {2022}, author = {Beneš, J and Stebel, R and Musil, V and Krůtová, M and Vejmelka, J and Kohout, P}, title = {[Updated Czech guidelines for the treatment of patients with colitis due to Clostridioides difficile].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {28}, number = {3}, pages = {77-94}, pmid = {36791303}, issn = {1211-264X}, abstract = {The updated Czech guidelines differ in some aspects from the 2021 guidelines issued by the ESCMID Study Group for Clostridium difficile. The key points of these Czech recommendations may be summarized as follows: • The drug of choice for hospitalized patients is orally administered fidaxomicin or vancomycin. In outpatients with a mild first episode of C. difficile infection, metronidazole can also be used. • If the patient's response to treatment is good and there are no complications, the duration of antibiotic treatment can be reduced (e.g. to 5 days in case of fidaxomicin or to 6-7 days in case of vancomycin). • If oral therapy is impossible, the drug of choice is tigecycline, 100 mg i.v., b.i.d., with initial shortening of the interval between the first and second doses for faster saturation. If the severity of the disease progresses during this antibiotic treatment, it is necessary to access the ileum or cecum, i.e. to perform double ileostomy or percutaneous endoscopic cecostomy, and to instill vancomycin or fidaxomicin lavages. • Fulminant C. difficile colitis should be treated with oral fidaxomicin ± tigecycline i.v. If peristalsis ceases, fidaxomicin should be administered into the ileum or cecum as described above. If sepsis develops, a broad-spectrum beta-lactam antibiotic (piperacillin/tazobactam, carbapenem) i.v. is added to topically administered fidaxomicin instead of tigecycline i.v.; at the same time, colectomy should be considered as the last resort. • To treat first recurrence, fidaxomicin or vancomycin is administered with a subsequent fecal microbiota transplant (FMT) from a healthy donor. For second or subsequent recurrence, administration of fidaxomicin is of little benefit; the therapy of choice is oral vancomycin and subsequent FMT. Prolonged vancomycin or fidaxomicin taper and pulse treatment is appropriate only when FMT cannot be performed.}, } @article {pmid36788674, year = {2023}, author = {Han, B and Zhang, X and Wang, L and Yuan, W}, title = {Dysbiosis of Gut Microbiota Contributes to Uremic Cardiomyopathy via Induction of IFNγ-Producing CD4[+] T Cells Expansion.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0310122}, pmid = {36788674}, issn = {2165-0497}, abstract = {Uremic cardiomyopathy (UCM) correlates with chronic kidney disease (CKD)-induced morbidity and mortality. Gut microbiota has been involved in the pathogenesis of certain cardiovascular disease, but the role of gut microbiota in the pathogenesis of UCM remains unknown. Here, we performed a case-control study to compare the gut microbiota of patients with CKD and healthy controls by 16S rRNA (rRNA) gene sequencing. To test the causative relationship between gut microbiota and UCM, we performed fecal microbiota transplantation (FMT) in 5/6th nephrectomy model of CKD. We found that opportunistic pathogens, particularly Klebsiella pneumoniae (K. pneumoniae), are markedly enriched in patients with CKD. FMT from CKD patients aggravated diastolic dysfunction in the mouse model. The diastolic dysfunction was associated with microbiome-dependent increases in heart-infiltrating IFNγ[+] CD4[+] T cells. Monocolonization with K. pneumoniae increased cardiac IFNγ[+] CD4[+] T cells infiltration and promoted UCM development of the mouse model. A probiotic Bifidobacterium animalis decreased the relative abundance of K. pneumoniae, reduced levels of cardiac IFNγ[+] CD4[+] T cells and ameliorated the severity of diastolic dysfunction in the mice. Thus, the aberrant gut microbiota in CKD patients, especially K. pneumoniae, contributed to UCM pathogenesis through the induction of heart-infiltrating IFNγ[+] CD4[+] T cells expansion, proposing that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in elucidating the etiology of UCM, and suggesting that modulation of the gut bacteria may serve as a promising target for the amelioration of UCM. IMPORTANCE Uremic cardiomyopathy (UCM) correlates tightly with increased mortality in patients with chronic kidney disease (CKD), yet the pathogenesis of UCM remains incompletely understood, limiting therapeutic approaches. Our study proposed that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in understanding etiology of UCM. There is a major need in future clinical trials of patients with CKD to explore if modulation of gut microbiota by fecal microbiota transplantation (FMT), probiotics or antibiotics can alleviate cardiac dysfunction, reduce mortality, and improve life quality.}, } @article {pmid36788638, year = {2023}, author = {Pottenger, S and Watts, A and Wedley, A and Jopson, S and Darby, AC and Wigley, P}, title = {Timing and delivery route effects of cecal microbiome transplants on Salmonella Typhimurium infections in chickens: potential for in-hatchery delivery of microbial interventions.}, journal = {Animal microbiome}, volume = {5}, number = {1}, pages = {11}, pmid = {36788638}, issn = {2524-4671}, support = {BB/R008914/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Exposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks. However, administration of microbiota transplant products in a hatchery setting may prove challenging. Effective administration strategies are dependent on key factors, such as; the age of chicks receiving interventions and mode of delivery. This study aimed to assess these two aspects to provide supporting evidence towards microbiome manipulation strategies for use in commercial hatcheries.

RESULTS: Manipulation of the microbiota between 4 and 72 h of hatch markedly reduced faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration of transplant material via spray or gel drop delivery systems had minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that all transplant groups had higher diversity and species richness than non-transplant groups during the first week of life and the early stages of infection with ST47/4.The relative abundance of the bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections.

CONCLUSIONS: This study demonstrated that administration of microbiome transplants, using methods that would align with hatchery practices, effectively reduced colonisation and shedding of Salmonella in chickens. Age of chicks at microbiome administration had limited effect on the diversity and composition of the microbiome and conferred protection against Salmonella infections. Traditional hatchery delivery systems, such as spray or gel-drop, are sufficient to transfer donor material, alter the microbiome and confer protection against Salmonella. This study helps highlight the opportunity for use of microbiome modification methods within the hatchery.}, } @article {pmid36786456, year = {2023}, author = {Chauhan, A and Garg, M}, title = {Editorial: faecal microbiota transplantation for recurrent C. difficile infections-getting the support that is needed.}, journal = {Alimentary pharmacology & therapeutics}, volume = {57}, number = {5}, pages = {585-586}, doi = {10.1111/apt.17341}, pmid = {36786456}, issn = {1365-2036}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Feces ; *Clostridium Infections/therapy ; }, } @article {pmid36780159, year = {2023}, author = {Sims, MD and Khanna, S and Feuerstadt, P and Louie, TJ and Kelly, CR and Huang, ES and Hohmann, EL and Wang, EEL and Oneto, C and Cohen, SH and Berenson, CS and Korman, L and Lee, C and Lashner, B and Kraft, CS and Ramesh, M and Silverman, M and Pardi, DS and De, A and Memisoglu, A and Lombardi, DA and Hasson, BR and McGovern, BH and von Moltke, L and , }, title = {Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.}, journal = {JAMA network open}, volume = {6}, number = {2}, pages = {e2255758}, pmid = {36780159}, issn = {2574-3805}, mesh = {Humans ; Adult ; Female ; Middle Aged ; Male ; *Clostridioides difficile ; Canada ; *Clostridium Infections/drug therapy/epidemiology ; Anti-Bacterial Agents/adverse effects ; *Microbiota ; }, abstract = {IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry.

INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI.

MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population.

RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]).

CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141.}, } @article {pmid36781906, year = {2023}, author = {Jeon, JH and Kaiser, EE and Waters, ES and Yang, X and Lourenco, JM and Fagan, MM and Scheulin, KM and Sneed, SE and Shin, SK and Kinder, HA and Kumar, A and Platt, SR and Ahn, J and Duberstein, KJ and Rothrock, MJ and Callaway, TR and Xie, J and West, FD and Park, HJ}, title = {Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2520}, pmid = {36781906}, issn = {2045-2322}, abstract = {Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.}, } @article {pmid36779996, year = {2023}, author = {Scharl, M}, title = {[Which microbiota-based therapies have proven to be effective today?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {36779996}, issn = {2731-7099}, abstract = {BACKGROUND: There is increasing interest in the microbiota (this includes bacteria, fungi and viruses) and microbiota-based therapies. The relationship between changes in the composition of the intestinal microbiota and the pathogenesis of various diseases is of specific interest. In particular, the possibilities offered by targeted manipulation of the microbiota composition as specific treatment approaches look promising.

OBJECTIVES: This review article summarizes the current data on microbiota-based therapies as well as the evidence-based treatment options applicable for certain diseases.

RESULTS: Current data on the clinical effectiveness of microbiota-based therapies varies greatly between different diseases. While certain therapies proved successful in the treatment of some diseases, the data is still insufficient on their effectiveness in other diseases. So far, the most successful treatment in this context is fecal microbiota transplantation with a success rate of 80-90% for the treatment of Clostridioides difficile colitis.

CONCLUSIONS: The correction of dysbioses of the intestinal microbiota could provide new possibilities for the treatment of diseases. However, due to the lack of a causal-functional understanding and the mainly descriptive knowledge to date, applications are still limited. The current clinical studies addressing the changes and the importance of intestinal microbiota could lead to new therapeutic options in the treatment of diverse diseases in the future.}, } @article {pmid36778473, year = {2023}, author = {Zhang, YJ and Bousvaros, A and Docktor, M and Kaplan, A and Rufo, PA and Leier, M and Weatherly, M and Zimmerman, L and Tu Nguyen, LT and Barton, B and Russell, G and Alm, EJ and Kahn, SA}, title = {Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.01.30.23285033}, pmid = {36778473}, abstract = {BACKGROUND: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn’s disease (CD) and ulcerative colitis (UC).

RESULTS: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data.

CONCLUSIONS: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.}, } @article {pmid36778328, year = {2023}, author = {Borin, JM and Liu, R and Wang, Y and Wu, TC and Chopyk, J and Huang, L and Kuo, P and Ghose, C and Meyer, JR and Tu, XM and Schnabl, B and Pride, DT}, title = {Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.02.03.527064}, pmid = {36778328}, abstract = {BACKGROUND: The gastrointestinal microbiome plays a significant role in numerous host processes and has an especially large impact on modulating the host metabolism. Prior studies have shown that when mice receive fecal transplants from obese donors that were fed high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes. These studies demonstrate the prominent role that the gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, studies have not measured the impact of gut viruses on these phenotypes. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow. By characterizing the mice’s gut bacterial biota and weight-gain phenotypes over time, we demonstrate that viruses can shape the gut bacterial community and affect weight gain or loss.

RESULTS: We gavaged mice longitudinally over 4 weeks while measuring their body weights and collecting fecal samples for 16S rRNA amplicon sequencing. We evaluated mice that were fed normal chow or high-fat diets, and gavaged each group with either chow-derived fecal viromes, HFD-derived fecal viromes, or phosphate buffered saline controls. We found a significant effect of gavage type, where mice fed chow but gavaged with HFD-derived viromes gained significantly more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained significantly less weight than their counterparts receiving HFD-derived viromes. These results were replicated in two separate experiments and the phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Notably, there were differences in Lachnospirales and Clostridia in mice fed chow but gavaged with HFD-derived fecal viromes, and in Peptostreptococcales, Oscillospirales, and Lachnospirales in mice fed HFD but gavaged with chow-derived fecal viromes. Due to methodological limitations, we were unable to identify specific bacterial species or strains that were responsible for respective phenotypic changes.

CONCLUSIONS: This study confirms that virome-mediated perturbations can alter the fecal microbiome in an in vivo model and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.}, } @article {pmid36777669, year = {2023}, author = {Lv, S and Zhang, Y and Zhang, Z and Meng, S and Pu, Y and Liu, X and Liu, L and Ma, Y and Liu, W and Jiang, L}, title = {Diversity of the fecal microbiota in Chinese ponies.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1102186}, pmid = {36777669}, issn = {2297-1769}, abstract = {INTRODUCTION: The gut microbiomes of equine are plentiful and intricate, which plays an important part in the growth. However, there is a relative lack of information on the microbial diversity in the pony's gut.

METHODS: In this article, 118 fecal samples from DeBa pony, NiQi pony and GuZh horse were studied by 16S rRNA amplicon sequencing.

RESULTS: Diversity analysis was used to determine the difference of gut microbiota composition among different breeds. Alpha diversity analysis showed that the gut microbiota of NiQi ponies were abundant and various. Beta diversity analysis showed that the microorganisms constitution of DeBa ponies was more similar to that of NiQi ponies. LDA Effect Size (LEfSe) analysis result that the microorganism biomarkers for NiQi pony at the genus level were Phascolarctobacterium, Paludibacter, and Fibrobacter; the bacterial biomarker for DeBa pony was Streptococcus and Prevotella; and the bacterial biomarkers for GuZh horses was Treponema, Treponema Mogibacterium, Adlercreutzia, and Blautia. The correlation analysis between genera with >1% abundance and horse height found that Streptococcus (P < 0.01), Treponema (P < 0.01), Coprococcus (P < 0.01), Prevotella (P < 0.01), Phascolarctobacterium (P < 0.01), and Mogibacterium (P < 0.01) were significantly associated with horses' height. The functional prediction results indicated that DeBa pony have a microbiota functional more similar to NiQi pony.

DISCUSSION: For the first time, our results announce the species composition and structure of the gut microbiota in Chinese ponies. At the same time, our results can provide theoretical reference for further understanding the healthy breeding, feeding management and disease prevention of horses.}, } @article {pmid36777348, year = {2023}, author = {Liu, B and Zhang, L and Yang, H and Zheng, H and Liao, X}, title = {Microbiota: A potential orchestrator of antidiabetic therapy.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {973624}, pmid = {36777348}, issn = {1664-2392}, abstract = {The gut microbiota, as a 'new organ' of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as pro/prebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.}, } @article {pmid36776780, year = {2023}, author = {de la Villa, S and Herrero, S and Muñoz, P and Rodríguez, C and Valerio, M and Reigadas, E and Álvarez-Uría, A and Alcalá, L and Marín, M and Olmedo, M and Kestler, M and Chamorro, E and Bouza, E}, title = {Real-world Use of Bezlotoxumab and Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.}, journal = {Open forum infectious diseases}, volume = {10}, number = {2}, pages = {ofad028}, pmid = {36776780}, issn = {2328-8957}, abstract = {BACKGROUND: We aimed to describe the frequency of use and effectiveness of bezlotoxumab (BZX) and fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) in real-world practice.

METHODS: This was a retrospective study conducted in a university hospital in which adult patients treated with BZX or FMT from January 2018 to April 2021 were included. The primary objective was to evaluate the effectiveness of BZX and FMT in preventing early (within 8 weeks) and late (within 1 year) CDI recurrences (rCDI). A multivariate analysis of risk factors for early recurrence was performed.

RESULTS: Of 1377 consecutive CDI episodes, 117 (8.5%) received BZX or FMT, with full information available for 100 of the episodes: 51 received BZX, and 49 received FMT. BZX was used mostly in immunosuppressed patients (66.7%) and in first episodes or first recurrences in 70.6% of the cases. FMT was prescribed only in CDI recurrences. Despite the different conditions of the patients, there were no significant differences between BZX and FMT in preventing early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). In the multivariate analysis, risk factors for recurrence were presence of ≥2 previous rCDI episodes (odds ratio [OR], 2.90; 95% CI, 1.03-8.63) and use of non-CDI antibiotics (OR, 3.45; 95% CI, 1.24-9.57).

CONCLUSIONS: BZX and FMT were infrequently used in real-world practice. Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations.}, } @article {pmid36774109, year = {2022}, author = {Kong, CY and Li, ZM and Chen, HL and Mao, YQ and Han, B and Guo, JJ and Wang, LS}, title = {An Energy-Restricted Diet Including Yogurt, Fruit, and Vegetables Alleviates High-Fat Diet-Induced Metabolic Syndrome in Mice by Modulating the Gut Microbiota.}, journal = {The Journal of nutrition}, volume = {152}, number = {11}, pages = {2429-2440}, doi = {10.1093/jn/nxac181}, pmid = {36774109}, issn = {1541-6100}, abstract = {BACKGROUND: The importance of the composition of an energy-restricted diet in the treatment of metabolic syndrome (MetS) is unknown.

OBJECTIVES: In this study we aimed to investigate the benefits of a novel dietary treatment (50% calorie restriction diet composed of yogurt, fruit, and vegetables [CR-YD]) in mice with MetS.

METHODS: Forty 7-wk-old male C57BL/6 J mice were randomly assigned to 4 groups (n = 10/group) that were fed for 14 wk ad libitum with a normal diet (ND; 10%:70%:20% energy from fat: carbohydrate: protein) or for 12 wk with a high-fat diet (HFD; 60:20:20) or the HFD followed by 2 wk of feeding with a 50% calorie-restricted HFD (CR-HFD) or YD (CR-YD, 21.2%:65.4%:13.4% energy). Body weight, fat deposition, hepatic steatosis, serum concentrations of inflammatory biomarkers, and glucose homeostasis were assessed. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in MetS.

RESULTS: The HFD group had 50% greater body weight and 475% greater fat deposition than the ND group (P < 0.05). Compared with the HFD group, the CR-HFD and CR-YD groups had 22% and 31% lower body weight and 49% and 75% less fat deposition, respectively (P < 0.05). Compared with the CR-HFD group, the CR-YD group had 11% lower body weight, 96% less fat deposition, 500% less hepatic steatosis, 75% lower glucose, and 450% more hepatic Akkermansia bacteria (P < 0.05). The CR-YD group also had 50% lower histopathology scores and 1.35-fold higher levels of Claudin4 than the CR-HFD group (P < 0.05). The HFD + CR-YD fecal group had 10.6% lower body weight, 119% lower steatosis, and 17.9% lower glucose (P < 0.05) than the HFD + CR-HFD fecal group.

CONCLUSIONS: Compared with CR alone, the CR-YD diet has a better therapeutic effect in mice with HFD-induced MetS.}, } @article {pmid36447381, year = {2023}, author = {Sever, A and Ben Zvi, H and Melamed, SB and Sachs, N and Krause, I and Bilavsky, E}, title = {Clinical impact of biofire gastrointestinal panel testing for hospitalised children with acute gastroenteritis.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {3}, pages = {505-509}, doi = {10.1111/apa.16610}, pmid = {36447381}, issn = {1651-2227}, mesh = {Child ; Humans ; Retrospective Studies ; Child, Hospitalized ; *Cryptosporidiosis ; Feces ; *Cryptosporidium ; *Gastroenteritis/diagnosis ; Diarrhea/etiology ; }, abstract = {AIM: To investigate the clinical impact of BioFire FilmArray Gastrointestinal Panel (FGP) testing in real-life diarrhoeal episodes of hospitalised paediatric patients.

METHODS: Children hospitalised between October 2018 and September 2020 for whom stool specimens for FGP were submitted at the clinician's discretion were retrospectively observed. For each episode, demographics, clinical information and stool tests were collected.

RESULTS: The clinical impact for each case was evaluated by changing the antibiotic prescription, following the result of the FGP testing. Out of 140 diarrhoeal episodes, 25 pathogens were found in 24 cases using conventional methods, whereas, FGP testing identified 75 pathogens in 56 cases (p < 0.05). The pathogens more frequently identified by FGP testing were Campylobacter, Shigella, Rotavirus, Giardia lamblia and Cryptosporidium. The clinical impact of FGP testing was observed in 17/140 (12%) diarrhoeal episodes, and higher rates in previously healthy (19%) and solid organ-transplanted children (15%).

CONCLUSION: We found that using FGP testing for hospitalised children with diarrhoeal episodes could increase pathogen identification and impact clinical decisions, especially in healthy and transplant patients.}, } @article {pmid36777748, year = {2020}, author = {Sood, A and Singh, A and Midha, V and Mahajan, R and Kao, D and Rubin, DT and Bernstein, CN}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: An Evolving Therapy.}, journal = {Crohn's & colitis 360}, volume = {2}, number = {4}, pages = {otaa067}, pmid = {36777748}, issn = {2631-827X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is currently an approved treatment for recurrent and refractory Clostridioides difficile infection. However, its use in ulcerative colitis is at an early stage and significant gaps remain in our understanding of the mechanisms and logistics of its practical application.

METHODS AND RESULTS: This article aims to look into specific issues which remain unsettled for use of FMT in ulcerative colitis including donor and recipient selection, route of administration, and duration of therapy. We also discuss optimal ways to assess response to FMT and the current state of FMT regulations. In addition, we postulate the impact of diet on the microbiome profile of the donor and recipient. We also suggest a change in the nomenclature from FMT to fecal microbiome transfer.

CONCLUSION: FMT is an evolving therapy. There are several considerations for its use in UC but its use and role should be directed by further clinical trials.}, } @article {pmid36777294, year = {2020}, author = {Kayal, M and Lambin, T and Pinotti, R and Dubinsky, MC and Grinspan, A}, title = {A Systematic Review of Fecal Microbiota Transplant for the Management of Pouchitis.}, journal = {Crohn's & colitis 360}, volume = {2}, number = {2}, pages = {otaa034}, pmid = {36777294}, issn = {2631-827X}, abstract = {BACKGROUND: Manipulation of the pouch microbiota via fecal microbiota transplant (FMT) has been theorized to be a promising therapeutic approach for pouchitis. The goal of this systematic review was to summarize the available, high-quality data on the efficacy and safety of FMT for acute and chronic pouchitis.

METHODS: A systematic electronic literature search was conducted on Embase, MEDLINE, Scopus, and Cochrane CENTRAL. Randomized controlled trials and observational studies that assessed the efficacy and safety of FMT for the treatment of acute and/or chronic pouchitis in patients with ulcerative colitis who underwent total proctocolectomy with ileal pouch-anal anastomosis were included.

RESULTS: Four studies involving the use of FMT for chronic pouchitis were considered eligible for data extraction. No study involving the use of FMT for the management of acute pouchitis was identified. In 1 study, 3/5 (75%) patients achieved sustained clinical remission at 3 months. In the remaining 3 studies, 2/8, 1/11, and 1/5 patients achieved clinical response defined as a decrease in pouchitis disease activity index at least 3. Stool donor engraftment as determined by 16s rRNA gene sequencing occurred only in those patients with clinical response.

CONCLUSIONS: The 4 studies that met inclusion criteria for this systematic review indicate FMT is safe in chronic pouchitis, however largely not efficacious. These data are limited by study heterogeneity. Additional studies are required to guide the use of FMT in patients with acute and chronic pouchitis.}, } @article {pmid36777298, year = {2020}, author = {Raffals, LE}, title = {Self-administered Fecal Microbial Transplants-What Could Possibly Go Wrong?.}, journal = {Crohn's & colitis 360}, volume = {2}, number = {2}, pages = {otaa025}, pmid = {36777298}, issn = {2631-827X}, } @article {pmid36771498, year = {2023}, author = {Yun, SW and Park, HS and Shin, YJ and Ma, X and Han, MJ and Kim, DH}, title = {Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition.}, journal = {Nutrients}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/nu15030790}, pmid = {36771498}, issn = {2072-6643}, abstract = {Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the β-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aβ expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the β-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis.}, } @article {pmid36771383, year = {2023}, author = {Wang, Y and Wang, X and Xiao, X and Yu, S and Huang, W and Rao, B and Chen, F}, title = {A Single Strain of Lactobacillus (CGMCC 21661) Exhibits Stable Glucose- and Lipid-Lowering Effects by Regulating Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/nu15030670}, pmid = {36771383}, issn = {2072-6643}, abstract = {Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new Lactobacillus (abbreviated as Lb., named as CGMCC No. 21661) after genetic testing. We designed the most common Bifidobacterium longum subsp. longum (CGMCC1.2186, abbreviated as B. longum. subsp.), fecal microbiota transplantation (FMT), and Lb. CGMCC No. 21661 protocols to explore the best way for modulating dysbiosis to improve T2D. After 6 weeks of gavage in T2D mice, it was found that all three protocols had a therapeutic alleviating effect. Among them, compared with the B. longum. subsp. and FMT, the Lb. CGMCC No. 21661 showed a 1- to 2-fold decrease in blood glucose (11.84 ± 1.29 mmol/L, p < 0.05), the lowest HOMA-IR (p < 0.05), a 1 fold increase in serum glucagon-like peptide-1 (5.84 ± 1.1 pmol/L, p < 0.05), and lowest blood lipids (total cholesterol, 2.21 ± 0.68 mmol/L, p < 0.01; triglycerides, 0.4 ± 0.15 mmol/L, p < 0.01; Low-density lipoprotein cholesterol, 0.53 ± 0.16 mmol/L, p < 0.01). In addition, tissue staining in the Lb. CGMCC No. 21661 showed a 2- to 3-fold reduction in T2D-induced fatty liver (p < 0.0001), a 1- to 2-fold decrease in pancreatic apoptotic cells (p < 0.05), and a significant increase in colonic mucus layer thickness (p < 0.05) compared with the B. longum. subsp. and FMT. The glucose and lipid lowering effects of this Lb. CGMCC No. 21661 indicate that it may provide new ideas for the treatment of diabetes.}, } @article {pmid36769429, year = {2023}, author = {Wang, W and Lu, G and Wu, X and Wen, Q and Zhang, F}, title = {Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, doi = {10.3390/jcm12030780}, pmid = {36769429}, issn = {2077-0383}, abstract = {The limitation of traditional delivery methods for fecal microbiota transplantation (FMT) gave birth to colonic transendoscopic enteral tubing (TET) to address the requirement of frequent FMTs. Colonic TET as a novel endoscopic intervention has received increasing attention in practice since 2015 in China. Emerging studies from multiple centers indicate that colonic TET is a promising, safe, and practical delivery method for microbial therapy and administering medication with high patient satisfaction. Intriguingly, colonic TET has been used to rescue endoscopy-related perforations by draining colonic air and fluid through the TET tube. Recent research based on collecting ileocecal samples through a TET tube has contributed to demonstrating community dynamics in the intestine, and it is expected to be a novel delivery of proof-of-concept in host-microbiota interactions and pharmacological research. The present article aims to review the concept and techniques of TET and to explore microbial therapy, colonic drainage, and microbial research based on colonic TET.}, } @article {pmid36768173, year = {2023}, author = {Panebianco, C and Villani, A and Potenza, A and Favaro, E and Finocchiaro, C and Perri, F and Pazienza, V}, title = {Targeting Gut Microbiota in Cancer Cachexia: Towards New Treatment Options.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, doi = {10.3390/ijms24031849}, pmid = {36768173}, issn = {1422-0067}, abstract = {Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients' response to anticancer treatments, quality of life, and overall survival. Despite its clinical relevance, cancer cachexia often remains an underestimated complication due to the lack of rigorous diagnostic and therapeutic pathways. A number of studies have shown alterations in gut microbiota diversity and composition in association with cancer cachexia markers and symptoms, thus supporting a central role for dysbiosis in the pathogenesis of this syndrome. Different tools of microbiota manipulation, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been investigated, demonstrating encouraging improvements in cachexia outcomes. Albeit pioneering, these studies pave the way for future research with the aim of exploring the role of gut microbiota in cancer cachexia more deeply and setting up effective microbiota-targeting interventions to be translated into clinical practice.}, } @article {pmid36768140, year = {2023}, author = {Majait, S and Nieuwdorp, M and Kemper, M and Soeters, M}, title = {The Black Box Orchestra of Gut Bacteria and Bile Acids: Who Is the Conductor?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, doi = {10.3390/ijms24031816}, pmid = {36768140}, issn = {1422-0067}, abstract = {Over the past decades the potential role of the gut microbiome and bile acids in type 2 diabetes mellitus (T2DM) has been revealed, with a special reference to low bacterial alpha diversity. Certain bile acid effects on gut bacteria concern cytotoxicity, or in the case of the microbiome, bacteriotoxicity. Reciprocally, the gut microbiome plays a key role in regulating the bile acid pool by influencing the conversion and (de)conjugation of primary bile acids into secondary bile acids. Three main groups of bacterial enzymes responsible for the conversion of bile acids are bile salt hydrolases (BSHs), hydroxysteroid dehydrogenases (HSDHs) and enzymes encoded in the bile acid inducible (Bai) operon genes. Interventions such as probiotics, antibiotics and fecal microbiome transplantation can impact bile acids levels. Further evidence of the reciprocal interaction between gut microbiota and bile acids comes from a multitude of nutritional interventions including macronutrients, fibers, prebiotics, specific individual products or diets. Finally, anatomical changes after bariatric surgery are important because of their metabolic effects. The heterogeneity of studies, diseases, bacterial species and (epi)genetic influences such as nutrition may challenge establishing specific and detailed interventions that aim to tackle the gut microbiome and bile acids.}, } @article {pmid36765735, year = {2023}, author = {Knisely, A and Seo, YD and Wargo, JA and Chelvanambi, M}, title = {Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/cancers15030777}, pmid = {36765735}, issn = {2072-6694}, abstract = {The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches.}, } @article {pmid36761896, year = {2023}, author = {Qian, W and Wu, M and Qian, T and Xie, C and Gao, Y and Qian, S}, title = {The roles and mechanisms of gut microbiome and metabolome in patients with cerebral infarction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1112148}, pmid = {36761896}, issn = {2235-2988}, abstract = {As the most common type of stroke, ischemic stroke, also known as cerebral infarction (CI), with its high mortality and disability rate, has placed a huge burden on social economy and public health. Treatment methods for CI mainly include thrombectomy, thrombolysis, drug therapy, and so on. However, these treatments have certain timeliness and different side effects. In recent years, the gut-brain axis has become a hot topic, and its role in nervous system diseases has been confirmed by increasing evidences. The intestinal microbiota, as an important part of the gut-brain axis, has a non-negligible impact on the progression of CI through mechanisms such as inflammatory response and damage-associated molecular patterns, and changes in the composition of intestinal microbiota can also serve as the basis for predicting CI. At the same time, the diagnosis of CI requires more high-throughput techniques, and the analysis method of metabolomics just fits this demand. This paper reviewed the changes of intestinal microbiota in patients within CI and the effects of the intestinal microbiota on the course of CI, and summarized the therapeutic methods of the intervention with the intestinal microbiota. Furthermore, metabolic changes of CI patients were also discussed to reveal the molecular characteristics of CI and to elucidate the potential pathologic pathway of its interference.}, } @article {pmid36758789, year = {2023}, author = {Ouyang, S and Wang, X and Chen, Y and Deng, L and Yang, X and Hu, S and Wu, S}, title = {Swimming training combined with fecal microbial transplantation protects motor functions in rats with spinal cord injury by improving the intestinal system.}, journal = {Neuroscience letters}, volume = {}, number = {}, pages = {137104}, doi = {10.1016/j.neulet.2023.137104}, pmid = {36758789}, issn = {1872-7972}, abstract = {Spinal cord injury (SCI) leads to severe intestinal dysfunction and decreased motility. There is an interaction between the intestine and the nervous system, intestinal intervention through microbial regulation and exercise is a potential treatment option for spinal cord injury. We investigated the effects of swimming rehabilitation training combined with fecal microbial transplantation on intestinal as well as neurological functions in rats with spinal cord injuries, and explored the potential mechanisms. The animals were randomly divided into five groups: sham-operated control group (Sham), spinal cord injury only group (SCI), swimming training group (Swimming), fecal microbial transplantation group (FMT) and combined interventions group (Combined). Behavioral assessments, pathological and immunological analyses were performed after the interventions. Compared to rats in the spinal cord injury group, rats subjected to swimming training, fecal microbial transplantation and combined interventions group exhibited improved intestinal transit, barrier functions, motility, and motor conduction pathway conductivity(P<0.05). The combined interventions group had better outcomes(P<0.01). In addition, combined interventions significantly suppressed inflammatory factor levels (P<0.05) in the colon and spinal cords and significantly protected forefoot motor neurons (NeuN) in the spinal cord injury area, inhibiting astrocyte activation and reducing the expressions of the signature glial fibrillary acidic protein (GFAP) and markers of microglia (Iba-1) at the lesion site(P<0.05). In conclusion, all effects of combined swimming training and fecal microbial transplantation interventions were superior to swimming training or fecal microbial transplantation alone. Swimming training and fecal microbial transplantation interventions have a synergistic effect on the recovery of intestinal function and motility after spinal cord injury. The mechanism of mutual facilitation between gut function and motility may be related to the brain-gut axis interaction.}, } @article {pmid36756616, year = {2023}, author = {Varga, A and Makszin, L and Bufa, A and Sipos, D and Kása, P and Pál, S and Rosenstiel, P and Sommer, F and Kocsis, B and Péterfi, Z}, title = {Efficacy of lyophilised bacteria-rich faecal sediment and supernatant with reduced bacterial count for treating patients with Clostridioides difficile Infection - A novel method for capsule faecal microbiota transfer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1041384}, pmid = {36756616}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation ; Bacterial Load ; Capsules ; *Clostridioides difficile ; Feces/microbiology ; *Clostridium Infections/therapy/microbiology ; Bacteria ; Lipids ; Treatment Outcome ; Recurrence ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transfer (FMT) has managed to earn its place in the Clostridioides difficile infection (CDI) guidelines by having comparable efficacy and recurrence rate of fidaxomicin. After more than 100 successful FMT administration through nasogastric tube, we started using hard gelatine capsules filled with lyophilised faecal sediment and supernatant. Our main question was whether uncoated capsules (containing faecal sediment or supernatant) are comparable to the widely used nasogastric tubes in CDI. We also investigated the effect of storage and time on the survival rate of bacteria in the samples.

METHODS: We compared the efficacy of our capsules to other treatment options of CDI at the Department of Infectology at the University of Pécs (Hungary). For our study, stool was collected from a single donor. We treated 10 patients with relapsing CDI, 5 of them received supernatant, 5 received sediment. Donor samples were stored on 4 different temperatures and tested to determine the survival rates of bacteria. As pilot projects, we also assessed the changes of bacterial taxa, protein- and lipid compositions. Moreover, we selected 4 patients to compare their samples prior and after FMT by using microbiome (16S amplicon sequencing), protein, and lipid analyses.

RESULTS: 4 out of the 5 patients who received supernatant became symptomless within 2 days after FMT. In the sediment group 3 out of 5 patients were cured from CDI. Comparing the supernatant to the sediment, we found significantly lower number of colony-forming units in the supernatant. We found that -80°C is the most suitable temperature to store the samples. The stool lipid profiles of recipients showed a more diverse composition after FMT, and changes in the stool protein profiles were observed as well. In the microbiome analysis, we observed an increase in the alpha diversity after FMT.

CONCLUSIONS: Our study of 10 patients showed good efficacy of lyophilised faecal supernatant using capsules. The single donor approach proved to be effective in our investigation. A significantly lower CFU number was sufficient for the effect, the separation can be achieved by widely available instruments. For storage temperature, -20°C was sufficient in our clinical practice.}, } @article {pmid36757537, year = {2023}, author = {Shao, T and Hsu, R and Hacein-Bey, C and Zhang, W and Gao, L and Kurth, MJ and Zhao, H and Shuai, Z and Leung, PSC}, title = {The Evolving Landscape of Fecal Microbial Transplantation.}, journal = {Clinical reviews in allergy & immunology}, volume = {}, number = {}, pages = {1-20}, pmid = {36757537}, issn = {1559-0267}, abstract = {The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.}, } @article {pmid36757169, year = {2023}, author = {Stulic, M and Culafic, D and Jordovic, J and Culafic, M and Petrovic, N and Stojimirov, I and Loncar, Z}, title = {West Nile Virus Infection in Liver Transplant Recipient With Neither De Novo Infection nor Donor-Derived Infection: A Case Report.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {21}, number = {1}, pages = {59-62}, doi = {10.6002/ect.2022.0226}, pmid = {36757169}, issn = {2146-8427}, abstract = {West Nile virus was first described in 1937 and has sinceperiodically appearedin variousparts oftheworld by infecting people and horses. Reported infection symptoms and signs may be highly variable, ranging from fever and myalgias to meningoencephalitis. A 59-year-old patient was admitted to the University Clinical Centre of Serbia, Belgrade, in September 2018, where livertransplantwasperformedtotreat cirrhosisof ethyl etiology. Immunosuppressive therapy was started immediately after successful transplant, with the patientreceiving methylprednisolone, tacrolimus, and mycophenolate mofetil. Mycophenolate mofetil was excluded from therapy on postoperative day 3 because of progressively worse white blood cell count. The patient became febrile on postoperative day 11 (39.6 °C), and arm tremor, nausea, vomiting, and frequent fluid stools occurred. He complained of pain in the muscles and joints of the lower extremities. The next day he experienced occasional disorientation. Neurological findings revealed no signs of acute focal neurological deficit. We performed culture tests to isolate pathological microorganisms, and results were negative in cultures of the blood, urine, feces, ascites, and a smear of the wound and tip of the central venous catheter. Lumbar puncture resulted in a clear cerebrospinal fluid that was sent for analysis that showed significant increases in white blood cell count (94 × 106 cells/L), total proteins (1.61 g/L), and microalbumin (504.5 mg/L), with a reduction of immunoglobulin G. On postoperative day 15, positive serology of West Nile virus immunoglobulin M in cerebrospinal fluid was verified. Intensive monitoring and symptomatic and supportive therapy resulted in clinical and laboratory improvement, and the patient was discharged in good general condition on postoperative day 22. Considering the high risk of posttransplant complications, there remains the question of whether all donors and recipients should be tested forWest Nile virus atthe onset oftransplant.}, } @article {pmid36755640, year = {2022}, author = {Kalra, SJS and Shankar, H and Mansoori, N and Gupta, DL}, title = {Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock.}, journal = {Drug target insights}, volume = {16}, number = {}, pages = {81-87}, pmid = {36755640}, issn = {1177-3928}, abstract = {The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and for the maturation and development of a fully functional immune system. Therefore, understanding the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive knowledge of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence displays an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.}, } @article {pmid36753681, year = {2023}, author = {Wang, Z and Yao, W and Sun, Y and Han, Y and Chen, X and Gong, P and Zhai, P and Pei, S and Xie, J and Ba, Q and Wang, H}, title = {Eucommia Bark/Leaf Extract Improves Lipid Metabolism Disorders by Affecting Intestinal Microbiota and Microbiome-Host Interaction in HFD Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c07239}, pmid = {36753681}, issn = {1520-5118}, abstract = {Eucommia bark contains many bioactive compounds and has anti-hyperlipidemic effects. However, due to the slow growth rate of the plant, there is a limited supply of this resource. Studies have demonstrated that Eucommia leaves contain active ingredients similar to those of Eucommia bark and also have anti-hyperlipidemic effects. It is not currently clear whether Eucommia leaf can be used as a substitute for Eucommia bark. Furthermore, their mechanism of action for anti-hyperlipidemia by improving the structure of the gut microbiota is also unclear. We aimed to determine the composition of the active ingredients in EBE and ELE by HPLC, establish an HFD-induced hyperlipidemia model, and combine fecal microbiota transplantation (FMT) experiments to investigate the mechanism of EBE/ELE anti-hyperlipidemia by modifying the structure of intestinal microbiota, as well as to compare the effects of EBE and ELE. Our results showed that EBE and ELE contained similar active ingredients and significantly alleviated lipid metabolism disorders and blood glucose levels in the HFD-induced hyperlipidemia model. In this study, EBE and ELE significantly reduced the relative abundance of Desulfovibrionaceae and Erysipelotrichaceae and significantly increased the relative abundance of Ruminococcaceae. They also promoted the production of short-chain fatty acids (SCFAs) and activated the gene expression of the SCFA receptors G protein-coupled receptor 41 (GPR41) and GPR43. In addition, EBE and ELE can significantly increase the expression of the fasting-induced adipose factor (Fiaf) gene in the colon and inhibit the secretion of lipoprotein lipase (LPL) in the liver, thereby inhibiting triglyceride (TG) synthesis. They also significantly activate the expression of GPR41 and GPR43 genes in the epididymal fat tissue, leading to reduced lipid accumulation in adipocytes. These effects on the target genes were associated with changes in the abundance of Desulfovibrionaceae, Erysipelotrichaceae, and Ruminococcaceae bacteria in the intestinal microbiota. Thus, regulating the relative abundance of these microbes may serve as prospective targets for EBE/ELE to influence the Fiaf-LPL gut-liver axis and the SCFAs-GPR41/GPR43 gut-fat axis. In addition, there was no significant difference in the anti-hyperlipidemic effects of ELE and EBE, suggesting that Eucommia leaf may be a suitable alternative to Eucommia bark for managing hyperlipidemia by regulating the structure of the intestinal microbiota. These findings suggest that Eucommia leaves have great potential for development as a functional food with lipid-lowering properties.}, } @article {pmid36752887, year = {2023}, author = {Garcia, N and Gutierrez, E}, title = {Anorexia nervosa and microbiota: systematic review and critical appraisal.}, journal = {Eating and weight disorders : EWD}, volume = {28}, number = {1}, pages = {1}, pmid = {36752887}, issn = {1590-1262}, abstract = {PURPOSE: Recent studies have reported a gut microbiota imbalance or dysbiosis associated with anorexia nervosa (AN), which has prompted an appraisal of its aetiological role, and the reformulation of AN as a metabo-psychiatric disorder. Thus, the aim of this paper was to critically review the current scientific findings regarding the role of microbiota in anorexia nervosa.

METHODS: A systematic study of peer-reviewed literature published in four databases between 2009 and 2022 was conducted according to PRISMA guidelines. Both human and animal studies were included.

RESULTS: A total of 18 studies were included. In animal models, both the preclinical and clinical findings were inconsistent regarding microbiota composition, faecal metabolite concentrations, and the effects of human faecal microbiota transplants.

CONCLUSION: The methodological limitations, lack of standardisation, and conceptual ambiguity hinder the analysis of microbiota as a key explanatory factor for AN.

LEVEL OF EVIDENCE: Level I, systematic review.}, } @article {pmid36752740, year = {2023}, author = {Liu, D and Tian, Q and Liu, K and Ren, F and Liu, G and Zhou, J and Yuan, L and Fang, Z and Zou, B and Wang, S}, title = {Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c07766}, pmid = {36752740}, issn = {1520-5118}, abstract = {Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement. Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.}, } @article {pmid36751730, year = {2023}, author = {Nørgaard, JC and Jørgensen, M and Moestrup, KS and Ilett, EE and Zucco, AG and Marandi, RZ and Julian, MN and Paredes, R and Lundgren, JD and Sengeløv, H and MacPherson, C}, title = {Impact of antibiotic treatment on the gut microbiome and its resistome in hematopoietic stem cell transplant recipients.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiad033}, pmid = {36751730}, issn = {1537-6613}, abstract = {Antibiotic resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics. The 13 most frequently used antibiotics were significantly associated with 154 (40% of tested associations) microbiome features. Use of broad-spectrum beta-lactam antibiotics was most markedly associated with microbial disruption and increase in resistome features. The enterococcal vanA gene was positively associated with eight of the 13 antibiotics, and in particular piperacillin/tazobactam and vancomycin. Here, we highlight the need for a high-resolution approach in understanding the development of antibiotic resistance in the gut microbiome. Our findings can be used to inform antibiotic stewardship and combat the increasing threat of antibiotic resistance.}, } @article {pmid36746362, year = {2023}, author = {Ma, J and Liu, Z and Gao, X and Bao, Y and Hong, Y and He, X and Zhu, W and Li, Y and Huang, W and Zheng, N and Sheng, L and Zhou, B and Chen, H and Li, H}, title = {Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106687}, doi = {10.1016/j.phrs.2023.106687}, pmid = {36746362}, issn = {1096-1186}, abstract = {Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. DATA AVAILABILITY STATEMENT: The data of RNAseq and 16S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.}, } @article {pmid36742327, year = {2023}, author = {Morse, ZJ and Simister, RL and Crowe, SA and Horwitz, MS and Osborne, LC}, title = {Virus induced dysbiosis promotes type 1 diabetes onset.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1096323}, pmid = {36742327}, issn = {1664-3224}, abstract = {Autoimmune disorders are complex diseases of unclear etiology, although evidence suggests that the convergence of genetic susceptibility and environmental factors are critical. In type 1 diabetes (T1D), enterovirus infection and disruption of the intestinal microbiota are two environmental factors that have been independently associated with T1D onset in both humans and animal models. However, the possible interaction between viral infection and the intestinal microbiota remains unknown. Here, we demonstrate that Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice, induced restructuring of the intestinal microbiome prior to T1D onset. Microbiome restructuring was associated with an eroded mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased circulating and intestinal commensal-reactive antibodies. The CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, implying a mutual "diabetogenic" microbiome. Notably, members of the Bifidobacteria and Akkermansia genera emerged as conspicuous members of this diabetogenic microbiome, implicating these taxa, among others, in diabetes onset. Further, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice enhanced T1D susceptibility and led to diminished expression of the short chain fatty acid receptor GPR43 and fewer IL-10-expressing regulatory CD4[+] T cells in the intestine of naïve NOD recipients. These findings support an overlap in known environmental risk factors of T1D, and suggest that microbiome disruption and impaired intestinal homeostasis contribute to CVB-enhanced autoreactivity and T1D.}, } @article {pmid36737985, year = {2023}, author = {Wang, L and Zhang, P and Chen, J and Li, C and Tian, Y and Xu, F}, title = {Prebiotic properties of the polysaccharide from Rosa roxburghii Tratt fruit and its protective effects in high-fat diet-induced intestinal barrier dysfunction: A fecal microbiota transplantation study.}, journal = {Food research international (Ottawa, Ont.)}, volume = {164}, number = {}, pages = {112400}, doi = {10.1016/j.foodres.2022.112400}, pmid = {36737985}, issn = {1873-7145}, abstract = {Polysaccharide from Rosa roxburghii Tratt fruit (RTFP) ameliorates high-fat diet (HFD)-induced colitis in mice. However, it is still unknown whether the gut microbiota can mediate the anti-colitis effects of RTFP in mice. This research aims to investigate the role of gut microbes in modulating RTFP in colitis mice through fecal microbiota transplantation (FMT). The findings demonstrated that RTFP exhibited prebiotic effects on HFD-induced colitis mice. After FMT treatment (transplatation of the microbiota from the fecal sample to each recipient daily), the fecal microbiota of RTFP-treated donor mice remarkably alleviated colitis-related symptoms (e.g., colonic inflammation, loss of body weight, gut microbiota dysbiosis, and loss of barrier integrity) and upregulated the expression of tight junction proteins compared to the HFD-treated donor mice. Overall, RTFP can reduce the severity of HFD-induced colitis by regulating gut microbiota.}, } @article {pmid36737487, year = {2023}, author = {Poto, R and Laniro, G and de Paulis, A and Spadaro, G and Marone, G and Gasbarrini, A and Varricchi, G}, title = {Is there a role for microbiome-based approach in common variable immunodeficiency?.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10238-023-01006-3}, pmid = {36737487}, issn = {1591-9528}, abstract = {Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.}, } @article {pmid36736919, year = {2023}, author = {Krishaa, L and Ng, TKS and Wee, HN and Ching, J}, title = {Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer's disease pathology: review and recommendations.}, journal = {Mechanisms of ageing and development}, volume = {}, number = {}, pages = {111787}, doi = {10.1016/j.mad.2023.111787}, pmid = {36736919}, issn = {1872-6216}, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests that the gut microbiome (GM) plays a pivotal role in the pathogenesis of AD through the microbiota-gut-brain axis (MGB). Alterations in GM composition and diversity have been observed in both animal models and in human patients with AD. GM dysbiosis has been implicated in increased intestinal permeability, blood-brain barrier (BBB) impairment, neuroinflammation and the development of hallmarks of AD. Further elucidation of the role of GM in AD could pave way for the development of holistic predictive methods for determining AD risk and progression of disease. Furthermore, accumulating evidence suggests that GM modulation could alleviate adverse symptoms of AD or serve as a preventive measure. In addition, increasing evidence shows that Type 2 Diabetes Mellitus (T2DM) is often comorbid with AD, with common GM alterations and inflammatory response, which could chart the development of GM-related treatment interventions for both diseases. We conclude by exploring the therapeutic potential of GM in alleviating symptoms of AD and in reducing risk. Furthermore, we also propose future directions in AD research, namely fecal microbiota transplantation (FMT) and precision medicine.}, } @article {pmid36735734, year = {2023}, author = {Lee, C and Kim, S and Kim, B and Holzapfel, WH and Hyun, CK}, title = {Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0280850}, doi = {10.1371/journal.pone.0280850}, pmid = {36735734}, issn = {1932-6203}, abstract = {Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.}, } @article {pmid36735599, year = {2023}, author = {Kahn, SA and Bousvaros, A}, title = {Topic of the month: How to write an effective letter of medical necessity.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003724}, pmid = {36735599}, issn = {1536-4801}, abstract = {Insurance companies and pharmacy benefit managers frequently deny prescriptions that are medically necessary but expensive. Physicians may appeal denials by providing insurers with additional clinical information and supporting medical evidence. One component of the appeal process is a well-written letter of medical necessity. The review article below provides guidance for the clinician to write a compelling and powerful letter. Among other components, the letter should include a clear description of the patient's specific case, the medical literature that supports the prescribing physician's choice of therapy, and the adverse consequences (e.g., hospitalization) if the patient does not get the needed medication.}, } @article {pmid36732497, year = {2023}, author = {Xu, Y and Wang, J and Wu, X and Jing, H and Zhang, S and Hu, Z and Rao, L and Chang, Q and Wang, L and Zhang, Z}, title = {Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2168101}, doi = {10.1080/19490976.2023.2168101}, pmid = {36732497}, issn = {1949-0984}, abstract = {Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.}, } @article {pmid36732495, year = {2023}, author = {Dong, TS and Katzka, W and Yang, JC and Chang, C and Arias-Jayo, N and Lagishetty, V and Balioukova, A and Chen, Y and Dutson, E and Li, Z and Mayer, EA and Pisegna, JR and Sanmiguel, C and Jacobs, JP}, title = {Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167170}, doi = {10.1080/19490976.2023.2167170}, pmid = {36732495}, issn = {1949-0984}, abstract = {Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.}, } @article {pmid36728562, year = {2023}, author = {Yang, W and Ren, D and Shao, H and Zhang, X and Li, T and Zhang, L and Liu, L and Zhao, Y and Niu, P and Yang, X}, title = {Theabrownin from Fu Brick Tea Improves Ulcerative Colitis by Shaping the Gut Microbiota and Modulating the Tryptophan Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c06821}, pmid = {36728562}, issn = {1520-5118}, abstract = {Fu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.}, } @article {pmid36726574, year = {2022}, author = {Han, TR and Yang, WJ and Tan, QH and Bai, S and Zhong, H and Tai, Y and Tong, H}, title = {Gut microbiota therapy for nonalcoholic fatty liver disease: Evidence from randomized clinical trials.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1004911}, pmid = {36726574}, issn = {1664-302X}, abstract = {Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, but there are no medications approved for treatment. Gut microbiota would be a novel and promising therapeutic target based on the concept of the gut-liver axis in liver disease. We reviewed randomized controlled trials on gut microbiota therapy in NAFLD in this study to evaluate its efficacy and plausibility in NAFLD.}, } @article {pmid36725289, year = {2023}, author = {Zhao, Q and Hao, Y and Yang, XQ and Yan, XY and Qiu, YL}, title = {[Preliminary study on the effect of fecal microbiota transplantation on neurobehavior and gut microbiota of offspring rats exposed to arsenic].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {1}, pages = {14-20}, doi = {10.3760/cma.j.cn121094-20220311-00125}, pmid = {36725289}, issn = {1001-9391}, abstract = {Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.}, } @article {pmid36725206, year = {2023}, author = {Peng, Y and Dong, W and Chen, G and Mi, J and Lu, L and Xie, Z and Xu, W and Zhou, W and Sun, Y and Zeng, X and Cao, Y and Yan, Y}, title = {Anthocyanins from Lycium ruthenicum Murray Ameliorated High-Fructose Diet-Induced Neuroinflammation through the Promotion of the Integrity of the Intestinal Barrier and the Proliferation of Lactobacillus.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c06713}, pmid = {36725206}, issn = {1520-5118}, abstract = {In the present study, we found that anthocyanins from Lycium ruthenicum Murray (ACN) potently ameliorated a high-fructose diet (HFrD)-induced neuroinflammation in mice. ACN improved the integrity of the intestinal barrier and suppressed the toll-like receptor 4 (TLR4) signaling pathway to ameliorate the neuroinflammation, which was verified by Tlr4[-/-] mice. Furthermore, ACN could modulate the HFrD-induced dysbiosis of gut microbiota. The fecal microbiota transplantation from ACN-induced mice was sufficient to attenuate the neuroinflammation, while the amelioration of neuroinflammation by ACN was blocked upon gut microbiota depletion. In addition, ACN-induced increment of the relative abundance of Lactobacillus might be responsible for the alleviation of the neuroinflammation, which was further confirmed in the promoting effect of ACN on the growth of Lactobacillus in vitro. Overall, these results provided the evidence of a comprehensive cross-talk mechanism between ACN and neuroinflammation in HFrD-fed mice, which was mediated by reducing gut microbiota dysbiosis and maintaining the intestinal barrier integrity.}, } @article {pmid36722516, year = {2023}, author = {Kwa, WT and Sundarajoo, S and Toh, KY and Lee, J}, title = {Application of emerging technologies for gut microbiome research.}, journal = {Singapore medical journal}, volume = {64}, number = {1}, pages = {45-52}, doi = {10.4103/singaporemedj.SMJ-2021-432}, pmid = {36722516}, issn = {0037-5675}, abstract = {Microbiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.}, } @article {pmid36721210, year = {2023}, author = {Pi, Y and Wu, Y and Zhang, X and Lu, D and Han, D and Zhao, J and Zheng, X and Zhang, S and Ye, H and Lian, S and Bai, Y and Wang, Z and Tao, S and Ni, D and Zou, X and Jia, W and Zhang, G and Li, D and Wang, J}, title = {Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {19}, doi = {10.1186/s40168-022-01458-x}, pmid = {36721210}, issn = {2049-2618}, abstract = {BACKGROUND: Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown.

OBJECTIVE: In the present study, we aimed to investigate the metabolism, therapeutic potential, and mechanisms of action of bile acids (BAs) in LBW-induced intestinal inflammation in a piglet model.

METHODS: The fecal microbiome and BA profile between LBW and normal birth weight (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed to further confirm the linkage between microbial BA metabolism and intestinal inflammation. The therapeutic potential of ursodeoxycholic acid (UDCA), a highly differentially abundant BA between LBW and NBW piglets, in alleviating colonic inflammation was evaluated in both LBW piglets, an LBW-FMT mice model, and a DSS-induced colitis mouse model. The underlying cellular and molecular mechanisms by which UDCA suppresses intestinal inflammation were also investigated in both DSS-treated mice and a macrophage cell line. Microbiomes were analyzed by using 16S ribosomal RNA sequencing. Fecal and intestinal BA profiles were measured by using targeted BA metabolomics. Levels of farnesoid X receptor (FXR) were knocked down in J774A.1 cells with small interfering RNAs.

RESULTS: We show a significant difference in both the fecal microbiome and BA profiles between LBW and normal birth weight animals in a piglet model. Transplantation of the microbiota of LBW piglets to antibiotic-treated mice leads to intestinal inflammation. Importantly, oral administration of UDCA, a major BA diminished in the intestinal tract of LBW piglets, markedly alleviates intestinal inflammation in LBW piglets, an LBW-FMT mice model, and a mouse model of colitis by inducing M2 macrophage polarization. Mechanistically, UDCA reduces inflammatory cytokine production by engaging BA receptor FXR while suppressing NF-κB activation in macrophages.

CONCLUSIONS: These findings establish a causal relationship between LBW-associated intestinal abnormalities and dysbiosis, suggesting that restoring intestinal health and postnatal maldevelopment of LBW infants may be achieved by targeting intestinal microbiota and BA metabolism. Video Abstract.}, } @article {pmid36721179, year = {2023}, author = {Wang, X and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {17}, doi = {10.1186/s40168-022-01452-3}, pmid = {36721179}, issn = {2049-2618}, abstract = {Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.}, } @article {pmid36720452, year = {2023}, author = {Yang, JZ and Zhang, KK and He, JT and Chen, LJ and Ding, JF and Liu, JL and Li, JH and Liu, Y and Li, XW and Zhao, D and Xie, XL and Wang, Q}, title = {Obeticholic acid protects against methamphetamine-induced anxiety-like behavior by ameliorating microbiota-mediated intestinal barrier impairment.}, journal = {Toxicology}, volume = {486}, number = {}, pages = {153447}, doi = {10.1016/j.tox.2023.153447}, pmid = {36720452}, issn = {1879-3185}, abstract = {Methamphetamine (Meth) abuse can cause severe anxiety disorder and interfere with gut homeostasis. Obeticholic acid (OCA) has emerged as a protective agent against diet-related anxiety that improves gut homeostasis. The potential for OCA to ameliorate Meth-induced anxiety, and the microbial mechanisms involved, remain obscure. Here, C57/BL6 mice were intraperitoneally injected with Meth (15 mg/kg) to induce anxiety-like behavior. 16 S rRNA sequence analysis and fecal microbiome transplantation (FMT) were used to profile the gut microbiome and evaluate its effects, respectively. Orally administered OCA was investigated for protection against Meth-induced anxiety. Results indicated that Meth mediated anxiety-like behavior, aroused hippocampal neuroinflammation through activation of the TLR4/MyD88/NF-κB pathway, weakened intestinal barrier and disturbed the gut microbiome. Specifically, abundance of anxiety-related Rikenella was increased. FMT from Meth-administrated mice also weakened intestinal barrier and elevated serum LPS, inducing hippocampal neuroinflammation and anxiety-like behavior in recipient mice. Finally, OCA pretreatment ameliorated Meth-induced impairment of gut homeostasis by reshaping the microbial composition and improving the intestinal barrier. Meth-induced anxiety-like behavior and hippocampal neuroinflammation were also ameliorated by OCA pretreatment. These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety.}, } @article {pmid36720105, year = {2023}, author = {Conover, KR and Absah, I and Ballal, S and Brumbaugh, D and Cho, S and Cardenas, MC and Knackstedt, ED and Goyal, A and Jensen, MK and Kaplan, JL and Kellermayer, R and Kociolek, LK and Michail, S and Oliva-Hemker, M and Reed, AW and Weatherly, M and Kahn, SA and Nicholson, MR}, title = {FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIOIDES DIFFICILE INFECTION IN IMMUNOCOMPROMISED PEDIATRIC PATIENTS.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003714}, pmid = {36720105}, issn = {1536-4801}, abstract = {OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.

METHODS: This is a multi-center retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.

RESULTS: Of 59 pediatric patients identified at nine centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after one or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; four (9.5%) of which were likely treatment-related. There were no deaths or infections with multi-drug resistant organisms during follow-up and all patients with a serious adverse event fully recovered.

CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.}, } @article {pmid36719820, year = {2023}, author = {Rokkas, T and Hold, GL}, title = {A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome.}, journal = {European journal of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000002519}, pmid = {36719820}, issn = {1473-5687}, abstract = {BACKGROUND: Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS.

AIM: We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS.

METHODS: Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored.

RESULTS: Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%).

CONCLUSION: The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.}, } @article {pmid36717922, year = {2023}, author = {Xu, QQ and Su, ZR and Yang, W and Zhong, M and Xian, YF and Lin, ZX}, title = {Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer's disease via modulating neuropathology and gut microbiota through suppressing C/EBPβ/AEP pathway.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {19}, pmid = {36717922}, issn = {1742-2094}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway.

METHODS: After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBPβ/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/β were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBPβ. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA.

RESULTS: Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (Aβ) 40 and Aβ42, suppressed Aβ plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBPβ/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBPβ in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice.

CONCLUSION: All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing Aβ plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBPβ/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.}, } @article {pmid36717576, year = {2023}, author = {Sun, WL and Hua, S and Li, XY and Shen, L and Wu, H and Ji, HF}, title = {Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {477}, doi = {10.1038/s41467-023-36079-x}, pmid = {36717576}, issn = {2041-1723}, abstract = {Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.}, } @article {pmid36717202, year = {2023}, author = {}, title = {Early use of faecal microbiota transplantation for C. difficile infection.}, journal = {Drug and therapeutics bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1136/dtb.2023.000003}, pmid = {36717202}, issn = {1755-5248}, abstract = {Overview of: Baunwall SMD, Andreasen SE, Hansen MM, et al Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2022;7:1083-91.}, } @article {pmid36714122, year = {2022}, author = {Hocking, L and Wilcox, M and Petrosillo, N and Griffin, P and Steiner, T and Attara, G and Doré, J and Cabling, M and Stockwell, S and Romanelli, RJ and Marjanovic, S}, title = {Improving care for patients with Clostridioides difficile infection: A clinical practice and healthcare systems perspective.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1033417}, pmid = {36714122}, issn = {2296-858X}, abstract = {INTRODUCTION: Arriving at a C. difficile infection (CDI) diagnosis, treating patients and dealing with recurrences is not straightforward, but a comprehensive and well-rounded understanding of what is needed to improve patient care is lacking. This manuscript addresses the paucity of multidisciplinary perspectives that consider clinical practice related and healthcare system-related challenges to optimizing care delivery.

METHODS: We draw on narrative review, consultations with clinical experts and patient representatives, and a survey of 95 clinical and microbiology experts from the UK, France, Italy, Australia and Canada, adding novel multi-method evidence to the knowledge base.

RESULTS AND DISCUSSION: We examine the patient pathway and variations in clinical practice and identify, synthesize insights on and discuss associated challenges. Examples of key challenges include the need to conduct multiple tests for a conclusive diagnosis, treatment side-effects, the cost of some antibiotics and barriers to access of fecal microbiota transplantation, difficulties in distinguishing recurrence from new infection, workforce capacity constraints to effective monitoring of patients on treatment and of recurrence, and ascertaining whether a patient has been cured. We also identify key opportunities and priorities for improving patient care that target both clinical practice and the wider healthcare system. While there is some variety across surveyed countries' healthcare systems, there is also strong agreement on some priorities. Key improvement actions seen as priorities by at least half of survey respondents in at least three of the five surveyed countries include: developing innovative products for both preventing (Canada, Australia, UK, Italy, and France) and treating (Canada, Australia, and Italy) recurrences; facilitating more multidisciplinary patient care (UK, Australia, and France); updating diagnosis and treatment guidelines (Australia, Canada, and UK); and educating and supporting professionals in primary care (Italy, UK, Canada, and Australia) and those in secondary care who are not CDI experts (Italy, Australia, and France) on identifying symptoms and managing patients. Finally, we discuss key evidence gaps for a future research agenda.}, } @article {pmid36714101, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Falalyeyeva, T and Tsyryuk, O and Kovalchuk, O and Kobyliak, N and Abenavoli, L and Boccuto, L}, title = {Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: A randomized clinical trial.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1049849}, pmid = {36714101}, issn = {2296-858X}, abstract = {INTRODUCTION: Growing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC.

AIM: This study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC.

MATERIAL AND METHODS: Patients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy-mesalazine-at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score ≤2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes.

RESULTS: Clinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 ± 1.21 and in the FMT group-3.15±1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 ± 1.44 vs. 2.14 ± 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group.

CONCLUSIONS: FTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&draw=2&rank=4, identifier: NCT05538026.}, } @article {pmid36713461, year = {2022}, author = {Lou, X and Xue, J and Shao, R and Yang, Y and Ning, D and Mo, C and Wang, F and Chen, G}, title = {Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1063543}, pmid = {36713461}, issn = {1664-3224}, abstract = {OBJECTIVE: Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient's commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor.

METHODS: In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function.

RESULTS: Sepsis patients' gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1β and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis.

DISCCUSION: FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.}, } @article {pmid36713428, year = {2022}, author = {Li, N and Xu, S and Zhang, S and Zhu, Q and Meng, X and An, W and Fu, B and Zhong, M and Yang, Y and Lin, Z and Liu, X and Xia, J and Wang, J and You, T and Yan, C and Tang, H and Zhuang, G and Peng, Z}, title = {MSI2 deficiency in ILC3s attenuates DSS-induced colitis by affecting the intestinal microbiota.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {963379}, pmid = {36713428}, issn = {1664-3224}, abstract = {BACKGROUND: The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are generally believed to be related to immune dysfunction and intestinal microbiota disorder. However, the exact mechanism is not yet fully understood. The pathological changes associated with dextran sodium sulfate (DSS)-induced colitis are similar to those in human UC. As a subgroup of the innate immune system, group 3 innate lymphoid cells (ILC3s) are widely distributed in the lamina propria of the intestinal mucosa, and their function can be regulated by a variety of molecules. Musashi2 (MSI2) is a type of evolutionarily conserved RNA-binding protein that maintains the function of various tissue stem cells and is essential for postintestinal epithelial regeneration. The effect of MSI2 deficiency in ILC3s on IBD has not been reported. Thus, mice with conditional MSI2 knockout in ILC3s were used to construct a DSS-induced colitis model and explore its effects on the pathogenesis of IBD and the species, quantity and function of the intestinal microbiota.

METHODS: Msi2[flox/flox] mice (Msi2[fl/fl]) and Msi2[flox/flox]Rorc[Cre] mice (Msi2[ΔRorc]) were induced by DSS to establish the IBD model. The severity of colitis was evaluated by five measurements: body weight percentage, disease activity index, colon shortening degree, histopathological score and routine blood examination. The species, quantity and function of the intestinal microbiota were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples.

RESULTS: MSI2 was knocked out in the ILC3s of Msi2[ΔRorc] mice. The Msi2[ΔRorc] mice exhibited reductions in body weight loss, the disease activity index, degree of colon shortening, tissue histopathological score and immune cells in the peripheral blood compared to those of Msi2[fl/fl] mice after DSS administration. The 16S rRNA sequencing results showed that the diversity of the intestinal microbiota in DSS-treated Msi2[ΔRorc] mice changed, with the abundance of Firmicutes increasing and that of Bacteroidetes decreasing. The linear discriminant analysis effect size (LEfSe) approach revealed that Lactobacillaceae could be the key bacteria in the Msi2[ΔRorc] mouse during the improvement of colitis. Using PICRUST2 to predict the function of the intestinal microbiota, it was found that the functions of differential bacteria inferred by modeling were mainly enriched in infectious diseases, immune system and metabolic functions.

CONCLUSIONS: MSI2 deficiency in ILC3s attenuated DSS-induced colonic inflammation in mice and affected intestinal microbiota diversity, composition, and function, with Lactobacillaceae belonging to the phylum Firmicutes possibly representing the key bacteria. This finding could contribute to our understanding of the pathogenesis of IBD and provide new insights for its clinical diagnosis and treatment.}, } @article {pmid36713373, year = {2022}, author = {Jiang, L and Yuan, C and Ye, W and Huang, Q and Chen, Z and Wu, W and Qian, L}, title = {Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1061627}, pmid = {36713373}, issn = {1664-3224}, abstract = {INTRODUCTION: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.

METHODS: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.

RESULTS: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.

DISCUSSION: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.}, } @article {pmid36713364, year = {2022}, author = {Alam, MZ and Maslanka, JR and Abt, MC}, title = {Immunological consequences of microbiome-based therapeutics.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1046472}, pmid = {36713364}, issn = {1664-3224}, abstract = {The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient's microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.}, } @article {pmid36713166, year = {2022}, author = {Singh, V and Lee, G and Son, H and Koh, H and Kim, ES and Unno, T and Shin, JH}, title = {Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1103836}, pmid = {36713166}, issn = {1664-302X}, abstract = {Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.}, } @article {pmid36713033, year = {2023}, author = {Li, R and Liu, R and Chen, L and Wang, G and Qin, L and Yu, Z and Wan, Z}, title = {Microbiota from Exercise Mice Counteracts High-Fat High-Cholesterol Diet-Induced Cognitive Impairment in C57BL/6 Mice.}, journal = {Oxidative medicine and cellular longevity}, volume = {2023}, number = {}, pages = {2766250}, pmid = {36713033}, issn = {1942-0994}, abstract = {Gut microbes may be the critical mediators for the cognitive enhancing effects of exercise. Via fecal microbiota transplantation (FMT), this study is aimed at determining the mechanism of how voluntary exercise improved learning and memory ability impairment post a high-fat, high-cholesterol (HFHC) diet. The learning and memory abilities assessed via the Morris water maze in the FMT recipient group of voluntary exercising mice were improved compared to sedentary group. 16S rRNA gene sequencing results indicated that exercise-induced changes in gut microbiota distribution were transmissible, mainly in terms of elevated Lactobacillus, Lactobacillus, and Eubacterium nodatum, as well as decreased Clostrida_UCG-014 and Akkermansia after FMT. The neuroprotective effects of FMT were mainly related to the improved insulin signaling pathway (IRS2/PI3K/AKT) and mitochondrial function; inhibition of AQP4; decreased p-Tau at serine 396 and 404; increased BDNF, PSD95, and synaptophysin in the hippocampus; and also decreased HDAC2 and HDAC3 protein expressions in the nuclear and cytoplasmic fractions of the hippocampus. The findings of qRT-PCR suggested that exercise-induced gut microbes, on the one hand, elevated GPR109A and decreased GPR43 and TNF-α in the hippocampus. On the other hand, it increased GPR109A and GPR41 expressions in the proximal colon tissue. In addition, total short-chain fatty acid (SCFA), acetic acid, propionic acid, isobutyric acid, valeric acid, and isovaleric acid contents were also elevated in the cecum. In conclusion, exercise-induced alterations in gut microbiota play a decisive role in ameliorating HFHC diet-induced cognitive deficits. FMT treatment may be a new considerable direction in ameliorating cognitive impairment induced by exposure to HFHC diet.}, } @article {pmid36710337, year = {2023}, author = {Tian, F and Li, Y and Wang, Y and Yu, B and Song, J and Ning, Q and Jian, C and Ni, M}, title = {Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {10}, pmid = {36710337}, issn = {1476-0711}, abstract = {BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.

METHODS: Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.

RESULTS: The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.

CONCLUSIONS: The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.}, } @article {pmid36710269, year = {2023}, author = {Zhao, Q and Yu, J and Zhou, H and Wang, X and Zhang, C and Hu, J and Hu, Y and Zheng, H and Zeng, F and Yue, C and Gu, L and Wang, Z and Zhao, F and Zhou, P and Zhang, H and Huang, N and Wu, W and Zhou, Y and Li, J}, title = {Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {40}, pmid = {36710269}, issn = {2059-3635}, abstract = {The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.}, } @article {pmid36706918, year = {2023}, author = {Lu, T and Li, Q and Lin, W and Zhao, X and Li, F and Ji, J and Zhang, Y and Xu, N}, title = {Gut microbiota-derived glutamine attenuates liver ischemia/reperfusion injury via macrophage metabolic reprogramming.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcmgh.2023.01.004}, pmid = {36706918}, issn = {2352-345X}, abstract = {OBJECTIVE & AIMS: Many studies have revealed crucial roles of the gut microbiota and its metabolites in liver disease progression. However, the mechanism underlying their effects on liver ischemia/reperfusion (I/R) injury remain largely unknown. Here, we investigate the function of gut microbiota and its metabolites in liver I/R injury.

METHODS: C57BL/6 mice was pretreated with an antibiotic cocktail. Then, we used multi-omics detection methods including 16s rRNA sequencing, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) to explore the changes of gut microbiota and metabolites both in feces and portal blood in order to reveal the mechanism of their protective effect in liver I/R injury.

RESULTS: We found that antibiotic pretreatment (ABX) could significantly reduce the severity of I/R-induced hepatic injury, and this effect could be transferred to germ-free (GF) mice by fecal microbiota transplantation (FMT), suggesting a protective role of the gut microbiota depletion. During I/R, the rates of serum α-ketoglutarate (aKG) production and glutamate reduction, downstream products of gut microbiota-derived glutamine were more significant in the ABX mice. Then, we showed that aKG could promote alternative (M2) macrophage activation through oxidative phosphorylation (OXPHOS) and Oligomycin A could inhibit M2 macrophage polarization and reversed this protective effect.

CONCLUSIONS: These findings show that the gut microbiota and its metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming. Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators can be exploited for the treatment of liver I/R injury.}, } @article {pmid36704100, year = {2022}, author = {Wu, Z and Zhang, B and Chen, F and Xia, R and Zhu, D and Chen, B and Lin, A and Zheng, C and Hou, D and Li, X and Zhang, S and Chen, Y and Hou, K}, title = {Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1089991}, pmid = {36704100}, issn = {2235-2988}, abstract = {OBJECTIVES: Recent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin.

METHODS: A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study. Patients were followed up at baseline and week 4 after treatment. Blood and stool samples were collected and subject to analyze clinical parameters and microbial communities by metagenomic sequencing, respectively.

RESULTS: FMT alone and FMT plus metformin significantly improved the clinical indicators HOMA-IR and BMI in T2DM, besides fasting blood glucose, postprandial blood glucose, and hemoglobin A1c that were also controlled by metformin. Donor microbiota effectively colonized in T2DM with slightly higher colonization ration in FMT than FMT plus metformin within 4 weeks, resulting in increased microbial diversity and community changes from baseline after treatment. A total of 227 species and 441 species were significantly alerted after FMT and FMT plus metformin, respectively. FMT were significantly associated with the clinical parameters. Among them, Chlorobium phaeovibrioides, Bifidibacterium adolescentis and Synechococcus sp.WH8103 were potential due to their significantly negative correlations with HOMA-IR.

CONCLUSIONS: FMT with or without metformin significantly improve insulin resistance and body mass index and gut microbial communities of T2DM patients by colonization of donor-derived microbiota.}, } @article {pmid36701104, year = {2023}, author = {Fan, L and Zeng, X and Xu, G}, title = {Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {36701104}, issn = {1976-3794}, abstract = {The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.}, } @article {pmid36700221, year = {2022}, author = {Chen, L and Ruan, G and Cheng, Y and Yi, A and Chen, D and Wei, Y}, title = {The role of Th17 cells in inflammatory bowel disease and the research progress.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1055914}, pmid = {36700221}, issn = {1664-3224}, abstract = {Th17 cells play an important role in the abnormal immune response in inflammatory bowel disease (IBD) and are involved in the development and progression of inflammation and fibrosis. An increasing amount of data has shown that gut microbes are important parts of intestinal immunity and regulators of Th17 cellular immunity. Th17 cell differentiation is regulated by intestinal bacteria and cytokines, and Th17 cells regulate the intestinal mucosal immune microenvironment by secreting cytokines, such as IL-17, IL-21, and IL-26. Solid evidence showed that, regarding the treatment of IBD by targeting Th17 cells, the therapeutic effect of different biological agents varies greatly. Fecal bacteria transplantation (FMT) in the treatment of IBD has been a popular research topic in recent years and is safe and effective with few side effects. To further understand the role of Th17 cells in the progression of IBD and associated therapeutic prospects, this review will discuss the progress of related research on Th17 cells in IBD by focusing on the interaction and immune regulation between Th17 cells and gut microbiota.}, } @article {pmid36698844, year = {2022}, author = {Chopra, T and Hecht, G and Tillotson, G}, title = {Gut microbiota and microbiota-based therapies for Clostridioides difficile infection.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1093329}, pmid = {36698844}, issn = {2296-858X}, abstract = {Clostridioides difficile infection poses significant clinical challenges due to its recurrent nature. Current antibiotic management does not address the underlying issue, that of a disturbed gastrointestinal microbiome, called dysbiosis. This provides a supportive environment for the germination of C. difficile spores which lead to infection and toxin production as well as an array of other health conditions. The use of microbiome restoration therapies such as live biotherapeutics can reverse dysbiosis and lead to good clinical outcomes. Several such therapies are under clinical investigation.}, } @article {pmid36693853, year = {2023}, author = {Chadchan, SB and Naik, SK and Popli, P and Talwar, C and Putluri, S and Ambati, CR and Lint, MA and Kau, AL and Stallings, CL and Kommagani, R}, title = {Gut microbiota and microbiota-derived metabolites promotes endometriosis.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {28}, pmid = {36693853}, issn = {2058-7716}, abstract = {Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct impact of microbiota and microbiota-derived metabolites on the endometriosis disease progression is largely unknown. To understand the causal role of gut microbiota and endometriosis, we have implemented a novel model using antibiotic-induced microbiota-depleted (MD) mice to investigate the endometriosis disease progression. Interestingly, we found that MD mice showed reduced endometriotic lesion growth and, the transplantation of gut microbiota by oral gavage of feces from mice with endometriosis rescued the endometriotic lesion growth. Additionally, using germ-free donor mice, we indicated that the uterine microbiota is dispensable for endometriotic lesion growth in mice. Furthermore, we showed that gut microbiota modulates immune cell populations in the peritoneum of lesions-bearing mice. Finally, we found a novel signature of microbiota-derived metabolites that were significantly altered in feces of mice with endometriosis. Finally, we found one the altered metabolite, quinic acid promoted the survival of endometriotic epithelial cells in vitro and lesion growth in vivo, suggesting the disease-promoting potential of microbiota-derived metabolites. In summary, these data suggest that gut microbiota and microbiota-derived metabolome contribute to lesion growth in mice, possibly through immune cell adaptations. Of translational significance, these findings will aid in designing non-invasive diagnostics using stool metabolites for endometriosis.}, } @article {pmid36693599, year = {2023}, author = {Hou, Q and Huang, J and Zhao, L and Pan, X and Liao, C and Jiang, Q and Lei, J and Guo, F and Cui, J and Guo, Y and Zhang, B}, title = {Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106676}, doi = {10.1016/j.phrs.2023.106676}, pmid = {36693599}, issn = {1096-1186}, abstract = {Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24[-/-] progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.}, } @article {pmid36692308, year = {2023}, author = {Pensinger, DA and Fisher, AT and Dobrila, HA and Van Treuren, W and Gardner, JO and Higginbottom, SK and Carter, MM and Schumann, B and Bertozzi, CR and Anikst, V and Martin, C and Robilotti, EV and Chow, JM and Buck, RH and Tompkins, LS and Sonnenburg, JL and Hryckowian, AJ}, title = {Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0057022}, doi = {10.1128/iai.00570-22}, pmid = {36692308}, issn = {1098-5522}, abstract = {A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.}, } @article {pmid36678325, year = {2023}, author = {Daskova, N and Heczkova, M and Modos, I and Hradecky, J and Hudcovic, T and Kuzma, M and Pelantova, H and Buskova, I and Sticova, E and Funda, D and Golias, J and Drabonova, B and Jarkovska, J and Kralova, M and Cibulkova, I and Gojda, J and Cahova, M}, title = {Protective Effect of Vegan Microbiota on Liver Steatosis Is Conveyed by Dietary Fiber: Implications for Fecal Microbiota Transfer Therapy.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, pmid = {36678325}, issn = {2072-6643}, mesh = {Mice ; Animals ; Humans ; Fecal Microbiota Transplantation ; Vegans ; Inulin/pharmacology ; Dietary Fiber/pharmacology ; *Fatty Liver/prevention & control/drug therapy ; *Gastrointestinal Microbiome ; Diet, Western ; Glucose/pharmacology ; }, abstract = {Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.}, } @article {pmid36689162, year = {2023}, author = {Lin, MC and Peng, ZY and Chou, HC and Tsai, YT and Wei, YS and Wang, YS and Wang, YL and Chang, SJ and Chan, HL}, title = {Fecal Protein Analysis of Dusp6 Knockout C57BL/6J Mice by Metaproteomics.}, journal = {Applied biochemistry and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {36689162}, issn = {1559-0291}, abstract = {The research of obesity and gut microbiota has been carried out for years, yet the study process was in a slow pace for several challenges to conquer. As a complex status of disorder, the contributing factors refer to gut microbiota about obesity were controversial in a wide range. In terms of proteomics, 2D-DIGE technology is a powerful method for this study to identify fecal proteins from lean microbiota in Dusp6 knockout C57BL/6J mice, exploring the protein markers of the ability resisting to diet-induced obesity (DIO) transferred to the host mice after fecal microbiota transplantation. The results showed that the fecal microbiota expressed 289 proteins differentially with 23 proteins identified, which were considered to be the reasons to assist the microbiota exhibiting distinct behavior. By means of proteomics technology, we had found that differentially expressed proteins of lean microbiota determined the lean microbial behavior might be able to resist leaky gut. To sum up our study, the proteomics strategies offered as a tool to demonstrate and analyze the features of lean microbiota, providing new speculations in the behavior about the gut microbiota reacting to DIO.}, } @article {pmid36689003, year = {2023}, author = {Rajindrajith, S and Devanarayana, NM and Thapar, N and Benninga, MA}, title = {Myths and misconceptions about childhood constipation.}, journal = {European journal of pediatrics}, volume = {}, number = {}, pages = {}, pmid = {36689003}, issn = {1432-1076}, abstract = {Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.}, } @article {pmid36688695, year = {2023}, author = {Pan, J and Chui, L and Liu, T and Zheng, Q and Liu, X and Liu, L and Zhao, Y and Zhang, L and Song, M and Han, J and Huang, J and Tang, C and Tao, C and Zhao, J and Wang, Y}, title = {Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0354022}, doi = {10.1128/spectrum.03540-22}, pmid = {36688695}, issn = {2165-0497}, abstract = {The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of Oscillospira and Coprococcus and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that Oscillospira and Coprococcus were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. IMPORTANCE This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including Oscillospira and Coprococcus, and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.}, } @article {pmid36688692, year = {2023}, author = {Strahm, N and Didriksen, H and Fretheim, H and Molberg, Ø and Midtvedt, Ø and Farstad, IN and Midtvedt, T and Lundin, KEA and Aabakken, L and Błyszczuk, P and Distler, O and Kania, G and Hoffmann-Vold, AM}, title = {Effects of faecal microbiota transplantation on small intestinal mucosa in systemic sclerosis.}, journal = {Rheumatology (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/rheumatology/kead014}, pmid = {36688692}, issn = {1462-0332}, abstract = {OBJECTIVES: In systemic sclerosis (SSc), gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling.

METHODS: We analysed duodenal biopsies obtained pre- (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving intestinal infusion of FMT (n = 5) or placebo (n = 4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling.

RESULTS: In patients receiving FMT, the number of podoplanin and CD64-expressing cells in the mucosa were lower at week 2 compared to baseline. This decline in podoplanin- (r = 0.94) and CD64-positive (r = 0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T-cell receptor complex, and chemokine receptor, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16.

CONCLUSION: Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement.}, } @article {pmid36687192, year = {2023}, author = {Aydin, OC and Aydın, S and Barun, S}, title = {Role of natural products and intestinal flora on type 2 diabetes mellitus treatment.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {65-72}, pmid = {36687192}, issn = {2307-8960}, abstract = {Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.}, } @article {pmid36687179, year = {2023}, author = {Yan, XX and Wu, D}, title = {Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {47-56}, pmid = {36687179}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent, and debilitating disorder, and includes Crohn's disease and ulcerative colitis. The pathogenesis of IBD is closely associated with intestinal dysbiosis, but has not yet been fully clarified. Genetic and environmental factors can influence IBD patients' gut microbiota and metabolism, disrupt intestinal barriers, and trigger abnormal immune responses. Studies have reported the alteration of gut microbiota and metabolites in IBD, providing the basis for potential therapeutic options. Intestinal microbiota-based treatments such as pre/probiotics, metabolite supplementation, and fecal microbiota transplantation have been extensively studied, but their clinical efficacy remains controversial. Repairing the intestinal barrier and promoting mucosal healing have also been proposed. We here review the current clinical trials on intestinal microecology and discuss the prospect of research and practice in this field.}, } @article {pmid36686492, year = {2022}, author = {Wang, G and Wang, Y and Bai, J and Li, G and Liu, Y and Deng, S and Zhou, R and Tao, K and Xia, Z}, title = {Increased plasma genistein after bariatric surgery could promote remission of NAFLD in patients with obesity.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1024769}, pmid = {36686492}, issn = {1664-2392}, abstract = {BACKGROUND: Bariatric surgery is associated with a positive effect on the progress of non-alcoholic associated fatty liver disease (NAFLD). Although weight loss is the obvious mechanism, there are also weight-independent mechanisms.

METHODS: We collected blood samples from 5 patients with obesity before and 3 months after surgery and performed an LC-MS-based untargeted metabolomics test to detect potential systemic changes. We also constructed sleeve gastrectomy (SG) mice models. The plasma, liver and intestine samples were collected and analyzed by qPCR, ELISA and HPLC. Cohousing experiments and feces transplantation experiments were performed on mice to study the effect of gut microbiota. Genistein administration experiments were used to study the in vivo function of the metabolites.

RESULTS: Plasma genistein (GE) was identified to be elevated after surgery. Both clinical data and rodent models suggested that plasma GE is negatively related to the degree of NAFLD. We fed diet-induced obese (DIO) mice with GE, and we found that there was significant remission of NAFLD. Both in vivo and in vitro experiments showed that GE could restrict the inflammation state in the liver and thus relieve NAFLD. Finally, we used co-housing experiments to alter the gut microbiota in mice, and it was identified that sleeve gastrectomy (SG) mice had a special gut microbiota phenotype, which could result in higher plasma GE levels. By feces transplantation experiment (FMT), we found that only feces from the SG mice (and not from other lean mice) could induce higher plasma GE levels.

CONCLUSION: Our studies showed that SG but not calorie restriction could induce higher plasma GE levels by altering the gut microbiota. This change could promote NAFLD remission. Our study provides new insights into the systemic effects of bariatric surgery. Bariatric surgery could affect remote organs via altered metabolites from the gut microbiota. Our study also identified that additional supplement of GE after surgery could be a therapy for NAFLD.}, } @article {pmid36685764, year = {2022}, author = {Minuti, A and Brufani, F and Menculini, G and Moretti, P and Tortorella, A}, title = {The complex relationship between gut microbiota dysregulation and mood disorders: A narrative review.}, journal = {Current research in neurobiology}, volume = {3}, number = {}, pages = {100044}, pmid = {36685764}, issn = {2665-945X}, abstract = {Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions. These latter correlations may enable an interdisciplinary perspective in the clinical approach to such symptoms, as well as new treatment strategies, such as nutritional interventions, psychobiotics, antibiotics, as well as fecal microbiota transplantation.}, } @article {pmid36683718, year = {2023}, author = {Senchukova, MA}, title = {Microbiota of the gastrointestinal tract: Friend or foe?.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {19-42}, pmid = {36683718}, issn = {2219-2840}, abstract = {The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.}, } @article {pmid36683714, year = {2023}, author = {Luo, M and Xin, RJ and Hu, FR and Yao, L and Hu, SJ and Bai, FH}, title = {Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {144-156}, pmid = {36683714}, issn = {2219-2840}, abstract = {Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.}, } @article {pmid36683707, year = {2022}, author = {Chen, Q and Fan, Y and Zhang, B and Yan, C and Chen, Z and Wang, L and Hu, Y and Huang, Q and Su, J and Ren, J and Xu, H}, title = {Specific fungi associated with response to capsulized fecal microbiota transplantation in patients with active ulcerative colitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1086885}, pmid = {36683707}, issn = {2235-2988}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a novel microbial treatment for patients with ulcerative colitis (UC). In this study, we performed a clinical trial of capsulized FMT in UC patients to determine the association between the gut fungal community and capsulized FMT outcomes.

DESIGN: This study recruited patients with active UC (N = 22) and healthy individuals (donor, N = 9) according to the criteria. The patients received capsulized FMT three times a week. Patient stool samples were collected before (week 0) and after FMT follow-up visits at weeks 1, 4, and 12. Fungal communities were analysed using shotgun metagenomic sequencing.

RESULTS: According to metagenomic analysis, fungal community evenness index was greater in samples collected from patients, and the overall fungal community was clustered among the samples collected from donors. The dominant fungi in fecal samples collected from donors and patients were Ascomycota and Basidiomycota. However, capsulized FMT ameliorated microbial fungal diversity and altered fungal composition, based on metagenomic analysis of fecal samples collected before and during follow-up visits after capsulized FMT. Fungal diversity decreased in samples collected from patients who achieved remission after capsulized FMT, similar to samples collected from donors. Patients achieving remission after capsulized FMT had specific enrichment of Kazachstania naganishii, Pyricularia grisea, Lachancea thermotolerans, and Schizosaccharomyces pombe compared with patients who did not achieve remission. In addition, the relative abundance of P. grisea was higher in remission fecal samples during the follow-up visit. Meanwhile, decreased levels of pathobionts, such as Candida and Debaryomyces hansenii, were associated with remission in patients receiving capsulized FMT.

CONCLUSION: In the metagenomic analysis of fecal samples from donors and patients with UC receiving capsulized FMT, shifts in gut fungal diversity and composition were associated with capsulized FMT and validated in patients with active UC. We also identified the specific fungi associated with the induction of remission. ClinicalTrails.gov (NCT03426683).}, } @article {pmid36683147, year = {2023}, author = {Jin, J and Xu, Z and Zhang, L and Zhang, C and Zhao, X and Mao, Y and Zhang, H and Liang, X and Wu, J and Yang, Y and Zhang, J}, title = {Gut-derived β-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167172}, doi = {10.1080/19490976.2023.2167172}, pmid = {36683147}, issn = {1949-0984}, abstract = {Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to the formation of Aβ plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aβ in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aβ and several key proteins involved in Aβ metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aβ was detected throughout the gut in both mice and human, and gut Aβ42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aβ42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aβ combined with vagotomy was also performed to investigate the transmission of Aβ from gut to brain. The data showed that, in aged mice, the gut Aβ42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aβ in the brain, and gut microbiota can further upregulate gut Aβ production, thereby potentially contributing to AD pathogenesis.}, } @article {pmid36682132, year = {2022}, author = {Cao, S and Guo, D and Yin, H and Ding, X and Bai, S and Zeng, Q and Liu, J and Zhang, K and Mao, X and Wang, J}, title = {Improvement in ovarian function following fecal microbiota transplantation from high-laying rate breeders.}, journal = {Poultry science}, volume = {102}, number = {3}, pages = {102467}, doi = {10.1016/j.psj.2022.102467}, pmid = {36682132}, issn = {1525-3171}, abstract = {The underlying mechanism between the gut microbiota and reproductive function is not yet well-known. This study was conducted to investigate the effect of the administration of fecal microbiota transplantation (FMT) from highly laying rate donors on the cecal microbiota, intestinal health and ovarian function in broiler breeders. A total of 60 broiler breeders (53 wk of age) were selected by their laying rate [high (HP, 90.67 ± 0.69%; n = 10) and low (LP, 70.23 ± 0.87%; n = 20)]. The LP breeders were then be transplanted with fecal microbiota from HP hens (FMTHP; n = 10) or the same dosage of PBS (FMTCON; n = 10) for 28 d. The results revealed that FMT from HP donors increased egg-laying rate and serum hormone levels [17β-estradiol (E2), anti-Müller hormone], also decreased proinflammatory cytokine levels (interleukin-6, interleukin-8, tumor necrosis factor-α) of LP breeders (P < 0.05). The FMTHP group breeders had higher villus height, villus height/crypt depth ratio, and upregulated mRNA expression of jejunum barrier-related gene (ZO-2 and mucin-2) and estrogen, follicle-stimulating hormone (FSH) and anti-Müller hormone (AMH) receptor genes (ESR1, ESR2, FSHR, AMHR) (P < 0.05) than FMTCON group. FMT from HP donors led to higher mRNA expression of Bcl2 and sirtuin1 (SIRT1), while it downregulated the proapoptotic genes (Bax, caspase-3, caspase-8, and caspase-9) mRNA expressions in ovary compared with the FMTCON breeders (P < 0.05), and this pattern was also observed in HP donors. Also, HP breeder had higher observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group, while FMTHP can increase observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group (P < 0.05). The bacteria enrichment of Firmicutes (phylum), Bacteroidetes (phylum), Lactobacillus (genus), Enterococcus (genus), and Bacteroides (genus) were increased by FMTHP treatment. The genera Butyricicoccus, Enterococcus, and Lactobacillus were positively correlated with egg-laying rate. Therefore, cecal microbiomes of breeders with high egg-laying performance have more diverse activities, which may be related to the metabolism and health of the host; and FMT from high-yield donors can increase the hormone secretion, intestinal health, and ovarian function to improve egg-laying performance and the SIRT1-related apoptosis and cytokine signaling pathway were involved in this process.}, } @article {pmid36681571, year = {2023}, author = {Ferre-Aracil, C and El Hajra Martínez, I and Vera Mendoza, MI and Ramos Martínez, A and Muñez Rubio, E and Fernández-Cruz, A and Matallana Royo, V and García-Maseda, S and Sánchez Romero, I and Martínez Ruiz, R and Calleja Panero, JL}, title = {[Faecal microbiota transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice].}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimce.2022.01.004}, pmid = {36681571}, issn = {2529-993X}, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile (CD) infection. The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting.

METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the fecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started.

RESULTS: 15 FMT were performed in 13 patients. The mean age of the patients was 73 ± 19,4 years (range: 40-98 years); being 60% women. The indication for FMT was relapsing colitis due to CD in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the TMF was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48h in all cases. Post-transplant follow-up was 25.66 ± 17.5 months. No significant short or long-term complications were recorded at follow-up.

CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.}, } @article {pmid36680756, year = {2023}, author = {Liu, Z and Wang, T and Zhu, Y and Zhao, H and Zhou, Z and Wu, Q}, title = {Improvements in gut microbiota dysbiosis in aged mice transplanted with adipose-derived stem cells.}, journal = {Stem cells and development}, volume = {}, number = {}, pages = {}, doi = {10.1089/scd.2022.0257}, pmid = {36680756}, issn = {1557-8534}, abstract = {Adipose-derived stem cells (ASCs), as a cell therapy with considerable therapeutic potential, have received increasing attention in tissue repair, endocrine regulation, immune regulation, and aging and obesity research. Gut microbiota are present in all organisms and play important roles in the development of aging and obesity. Dysbiosis activates inflammatory pathways that may contribute to the development of aging and obesity. We used C57BL/6J mice of different ages to carry out the experiment. Young mice were used as donors for ASC. Feces from the three groups were collected for 16sRNA sequencing to analyze the species composition of intestinal microorganisms. Then, predicted metabolic pathways by PICRUSt2 using 16s rRNA gene sequences. Immune cell levels in abdominal adipose tissue was assessed by flow cytometry. The content of IL-6、TNF-α and LPS in serum was measured by ELISA kit. Our 16sRNA sequencing data showed restoration of gut microbiota diversity and an increase in beneficial flora (Akkermansia, Lactobacillus, Prevotella) 7 days after ASC transplantation. In addition, the inflammatory environment improved in older transplanted mice.}, } @article {pmid36680641, year = {2023}, author = {Campos-Madueno, EI and Moradi, M and Eddoubaji, Y and Shahi, F and Moradi, S and Bernasconi, OJ and Moser, AI and Endimiani, A}, title = {Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {36680641}, issn = {1435-4373}, abstract = {The clinical impact of infections due to extended-spectrum β-lactamase (ESBL)- and/or carbapenemase-producing Enterobacterales (Ent) has reached dramatic levels worldwide. Infections due to these multidrug-resistant (MDR) pathogens-especially Escherichia coli and Klebsiella pneumoniae-may originate from a prior asymptomatic intestinal colonization that could also favor transmission to other subjects. It is therefore desirable that gut carriers are rapidly identified to try preventing both the occurrence of serious endogenous infections and potential transmission. Together with the infection prevention and control countermeasures, any strategy capable of effectively eradicating the MDR-Ent from the intestinal tract would be desirable. In this narrative review, we present a summary of the different aspects linked to the intestinal colonization due to MDR-Ent. In particular, culture- and molecular-based screening techniques to identify carriers, data on prevalence and risk factors in different populations, clinical impact, length of colonization, and contribution to transmission in various settings will be overviewed. We will also discuss the standard strategies (selective digestive decontamination, fecal microbiota transplant) and those still in development (bacteriophages, probiotics, microcins, and CRISPR-Cas-based) that might be used to decolonize MDR-Ent carriers.}, } @article {pmid36678326, year = {2023}, author = {Ma, X and Yan, H and Hong, S and Yu, S and Gong, Y and Wu, D and Li, Y and Xiao, H}, title = {Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/nu15020456}, pmid = {36678326}, issn = {2072-6643}, abstract = {Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.}, } @article {pmid36677385, year = {2022}, author = {DuPont, HL and Jiang, ZD and Alexander, AS and DuPont, AW and Brown, EL}, title = {Intestinal IgA-Coated Bacteria in Healthy- and Altered-Microbiomes (Dysbiosis) and Predictive Value in Successful Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/microorganisms11010093}, pmid = {36677385}, issn = {2076-2607}, abstract = {IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of fecal product from well-screened, healthy donors administered to patients with dysbiosis, has been successful in engrafting the intestine with healthy microbiota and metabolites leading to improve health. Through FMT, IgA-coated bacteria have been transferred to recipients retaining their immune coating. The IgA-biome should be evaluated in FMT studies as these mucosal-associated bacteria are more likely to be associated with successful transplantation than free luminal organisms. Studies of the microbiome pre- and post-FMT should employ metagenomic methods that identify bacteria at least at the species level to better identify organisms of interest while allowing comparisons of microbiota data between studies.}, } @article {pmid36674775, year = {2023}, author = {Przybyciński, J and Drożdżal, S and Wilk, A and Dziedziejko, V and Szumilas, K and Pawlik, A}, title = {The Effect of the Gut Microbiota on Transplanted Kidney Function.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, doi = {10.3390/ijms24021260}, pmid = {36674775}, issn = {1422-0067}, abstract = {The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.}, } @article {pmid36674517, year = {2023}, author = {Matheson, JT and Holsinger, RMD}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Neurodegenerative Diseases: A Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, doi = {10.3390/ijms24021001}, pmid = {36674517}, issn = {1422-0067}, abstract = {Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut-brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the "diseased" gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.}, } @article {pmid36672796, year = {2022}, author = {Conti, G and D'Amico, F and Fabbrini, M and Brigidi, P and Barone, M and Turroni, S}, title = {Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/genes14010055}, pmid = {36672796}, issn = {2073-4425}, abstract = {Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantation) are then explored in order to optimize clinical outcomes in cancer patients. Anticancer technologies that exploit tumor-associated bacteria to target tumors and biotransform drugs are also briefly discussed. In the field of pharmacomicrobiomics, multi-omics strategies coupled with machine and deep learning are urgently needed to bring to light the interaction among gut microbiota, drugs, and host for the development of truly personalized precision therapies.}, } @article {pmid36672518, year = {2022}, author = {Boicean, A and Neamtu, B and Birsan, S and Batar, F and Tanasescu, C and Dura, H and Roman, MD and Hașegan, A and Bratu, D and Mihetiu, A and Mohor, CI and Mohor, C and Bacila, C and Negrea, MO and Fleaca, SR}, title = {Fecal Microbiota Transplantation in Patients Co-Infected with SARS-CoV2 and Clostridioides difficile.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/biomedicines11010007}, pmid = {36672518}, issn = {2227-9059}, abstract = {BACKGROUND: The COVID-19 pandemic has challenged the treatment of Clostridioides&nbsp;Difficile (CD)-infected patients given the increasing number of co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, fecal microbiota transplantation (FMT) shows promise in modulating the immune system's function and alleviating the burdens associated with this condition.

METHODS: To achieve this goal, we performed a comparative, retrospective, single-center study on 86 patients (admitted between January 2020 and March 2022). We based our approach on specific inclusion criteria: 1. The study group included 46 co-infected patients (COVID-19 and CD) receiving antibiotics and FMT; 2. In the control group, 40 co-infected patients received antibiotics only. Our results showed no significant group differences in terms of gender, age, risk factors such as cardiovascular and neurological diseases, type 2 diabetes, and obesity (p > 0.05), or in pre-treatment inflammatory status, evaluated by white blood cell (WBC) count and C-reactive protein (CRP) levels. We report a significant decrease in inflammatory syndrome (CRP, WBC) in coinfected patients receiving FMT in addition to antibiotics (p < 0.05), with a lower relapse rate and mitigation of cramping and abdominal pain (91.3%). In addition, a higher level of fibrinogen, persistent moderate abdominal pain (82.5%), and a significantly higher CD infection relapse rate (42.5%) were recorded in co-infected patients treated only with antibiotics (p < 0.05).

CONCLUSION: Our study provides new data to support the multiple benefits of FMT in the case of COVID-19 and CD co-infection by improving patients' quality of life and inflammatory syndrome.}, } @article {pmid36670104, year = {2023}, author = {Wang, J and Cao, Y and Hou, W and Bi, D and Yin, F and Gao, Y and Huang, D and Li, Y and Cao, Z and Yan, Y and Zhao, J and Kong, D and Lv, X and Huang, L and Zhong, H and Wu, C and Chen, Q and Yang, R and Wei, Q and Qin, H}, title = {Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic synapse signaling pathways.}, journal = {Translational psychiatry}, volume = {13}, number = {1}, pages = {17}, pmid = {36670104}, issn = {2158-3188}, abstract = {Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.}, } @article {pmid36656870, year = {2023}, author = {Zhao, C and Bao, L and Zhao, Y and Wu, K and Qiu, M and Feng, L and Zhang, N and Hu, X and Fu, Y}, title = {A fiber-enriched diet alleviates Staphylococcus aureus-induced mastitis by activating the HDAC3-mediated antimicrobial program in macrophages via butyrate production in mice.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1011108}, doi = {10.1371/journal.ppat.1011108}, pmid = {36656870}, issn = {1553-7374}, abstract = {Mounting evidence suggests that the gut microbiota plays an important role in the pathogenesis of mastitis, an important disease affecting the health of lactating women and the development of the dairy industry. However, the effect of the regulation of the gut microbiota by dietary components on mastitis development remains unknown. In this study, we found that a fiber-enriched diet alleviated Staphylococcus aureus (S. au)-induced mastitis in mice, which was dependent on the gut microbiota as depletion of the gut microbiota by antibiotics abolished this protective effect. Likewise, fecal microbiota transplantation (FMT) from high-inulin (HI)-treated mice (HIF) to recipient mice improved S. au-induced mastitis in mice. Consumption of an HI diet and HIF increased fecal short-chain fatty acid (SCFA) levels compared with the control group. Moreover, treatment with SCFAs, especially butyrate, alleviated S. au-induced mastitis in mice. Mechanistically, consumption of an HI diet enhanced the host antimicrobial program in macrophages through inhibiting histone deacetylase 3 by the production of butyrate. Collectively, our results suggest that modulation of the gut microbiota and its metabolism by dietary components is a potential strategy for mastitis intervention and serve as a basis for other infectious diseases.}, } @article {pmid36656270, year = {2022}, author = {Gangwani, MK and Aziz, M and Aziz, A and Priyanka, F and Weissman, S and Phan, K and Dahiya, DS and Ahmed, Z and Sohail, AH and Lee-Smith, W and Kamal, F and Javaid, T and Nawras, A and Hart, B}, title = {Fresh Versus Frozen Versus Lyophilized Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection: A Systematic Review and Network Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001777}, pmid = {36656270}, issn = {1539-2031}, abstract = {INTRODUCTION: Clostridium difficile Infection is a significant source of morbidity and mortality, which is on the rise. Fecal Microbiota Transplantation (FMT) is an alternative therapy to antibiotics with a high success rate and low relapse rate. Current data regarding the efficacy of the types of FMT used, namely fresh, frozen, and lyophilized is conflicting. Our review attempts to consolidate this data and highlight the most efficacious treatment currently available.

METHODOLOGY: MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, SciELO, the Korean Citation Index, and Global Index Medicus were systematically searched from inception through May 3, 2022. Studies in which patients are undergoing any form of FMT who had failed antibiotic treatment previously were included. Both pairwise (direct) and network (direct + indirect) meta-analysis were performed using a random effects model and DerSimonian-Laird approach. A frequentist approach was used for network meta-analysis. Risk differences with (RD) with 95% confidence interval (CI) were calculated.

RESULTS: A total of 8 studies, including 4 RCTs and 4 cohort studies, were included with a total of 616 patients. Fresh FMT was determined to be most successful with 93% efficacy 95% CI (0.913 to 0.999) followed by frozen with 88% efficacy 95% CI (0.857 to 0.947) and lyophilized with 83% efficacy 95% CI (0.745 to 0.910). The direct meta-analysis showed no statistically significant difference between fresh and frozen group. (RD -0.051 95% CI -0.116 to 0.014 P=0.178). No significant differences were noted in frozen versus lyophilized groups with an overall trend towards Fresh FM (RD -0.061 95% CI -0.038 to 0.160 P=0.617). On network meta-analysis, when compared with fresh group, a lower recovery rate was noted with both frozen group (RD -0.06 95% CI -0.11 to 0.00 P=0.05) and lyophilized group (RD -0.16 95% CI -0.27 to -0.05 P=0.01).

CONCLUSION: We conclude the efficacy of Frozen and Lyophilized preparations is high with no difference in direct comparison, and the relative efficacy reduction based on network analysis is outweighed by the safety, accessibility, and practicality of Frozen or Lyophilized preparations.}, } @article {pmid36654766, year = {2023}, author = {Hao, S and Yang, S and Zhang, N and Cheng, H}, title = {Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends.}, journal = {The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2023}, number = {}, pages = {6981721}, pmid = {36654766}, issn = {1712-9532}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis.

METHODS: FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research.

RESULTS: There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines.

CONCLUSION: With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers' and practitioners' future work in the rapidly evolving field of FMT.}, } @article {pmid36654598, year = {2022}, author = {Ferreira, A and Neves, MT and Baleiras, A and Malheiro, M and Martins, A}, title = {Fecal Microbiota Transplant in Immunotherapy-Resistant Melanoma: What Can We Expect in the Near Future?.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32586}, pmid = {36654598}, issn = {2168-8184}, abstract = {Melanoma is a malignancy of melanocytes, melanin-producing cells in the basal layer of the epidermis. Despite representing only 1% of skin cancers, melanoma is responsible for over 80% of skin cancer deaths. Treatment with immune checkpoint inhibitors (ICIs) that target the programmed death 1 (PD-1) protein and the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways drastically transformed the management of patients with advanced melanoma. Before the introduction of ICIs, the average life expectancy for a patient with advanced melanoma ranged from six to 12 months, and now, this average survival has increased to over six years. However, despite this outstanding clinical success, most patients with advanced melanoma treated with ICIs will experience disease progression, immediately or after an initial response to treatment. Nowadays, some studies have looked at the mechanism behind the resistance to immunotherapy, with the aim of developing new treatments to overcome it. Emerging data suggest that gut microbiota (GM) influences response to immunotherapy. Importantly, unlike tumor genomics, the GM is changeable; thus, modulation of the GM is an attractive approach to overcome immunotherapy resistance. One of these approaches is the fecal microbiota transplant (FMT), which consists of the exchange of manipulated feces from a donor to a recipient who has a disorder related to intestinal dysbiosis to directly change the recipient's gut microbial composition and confer a health benefit. This review pretends to discuss the clinical benefit of FMT in the treatment of immunotherapy-resistant melanoma and potential adverse effects, including recent and ongoing clinical trials.}, } @article {pmid36648505, year = {2023}, author = {Märtson, AG and da Silva Ferreira, AR and Veringa, A and Liu, L and Wardill, HR and Junier, LAT and van der Werf, TS and Harmsen, HJM and Sturkenboom, MGG and Span, LF and Tissing, WJE and Alffenaar, JC}, title = {Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.}, journal = {Annals of hematology}, volume = {}, number = {}, pages = {}, pmid = {36648505}, issn = {1432-0584}, abstract = {Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.}, } @article {pmid36647403, year = {2023}, author = {Wakil, A and Niazi, M and Meybodi, MA and Pyrsopoulos, NT}, title = {Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.}, journal = {Journal of clinical and experimental hepatology}, volume = {13}, number = {1}, pages = {116-126}, pmid = {36647403}, issn = {0973-6883}, abstract = {UNLABELLED: The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis.

CONCLUSION: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.}, } @article {pmid36641624, year = {2023}, author = {Uribe-Herranz, M and Beghi, S and Ruella, M and Parvathaneni, K and Salaris, S and Kostopoulos, N and George, SS and Pierini, S and Krimitza, E and Costabile, F and Ghirardi, G and Amelsberg, KV and Lee, YG and Pajarillo, R and Markmann, C and McGettigan-Croce, B and Agarwal, D and Frey, N and Lacey, SF and Scholler, J and Gabunia, K and Wu, G and Chong, E and Porter, DL and June, CH and Schuster, SJ and Bhoj, V and Facciabene, A}, title = {Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2023.01.012}, pmid = {36641624}, issn = {1525-0024}, abstract = {Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects CAR T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, the hematopoietic CD19[+]-A20 lymphoma and the CD19[+]-B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor associated antigens (TAAs) cross-presentation compared to CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naïve gut microbiota mice. Lastly, B-cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared to unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.}, } @article {pmid36641024, year = {2023}, author = {Zhao, H and Li, M and Liu, L and Li, D and Zhao, L and Wu, Z and Zhou, M and Jia, L and Yang, F}, title = {Cordyceps militaris polysaccharide alleviates diabetic symptoms by regulating gut microbiota against TLR4/NF-κB pathway.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {123241}, doi = {10.1016/j.ijbiomac.2023.123241}, pmid = {36641024}, issn = {1879-0003}, abstract = {The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has attracted increasing attention. In our work, one purified fraction a (AEPSa) was obtained from Cordyceps militaris polysaccharides, and its hypoglycemic activity and underlying mechanisms were investigated in high-fat diet (HFD)- and streptozotocin (STZ)-induced T2DM mice. The results revealed that AEPSa reshaped gut microbiota by increasing Allobaculum, Alistipes, Lachnospiraceae_NK4A136_group and norank_f_Muribaculaceae and decreasing Enterococcus and Ruminococcus_torques_group to inhibit the colonic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and upregulate intestinal tight junction protein expression, thereby improving glucose and serum lipid metabolism, hormone secretion and complications. Fecal microbiota transplantation (FMT) also confirmed these findings. These results indicated that symptomatic relief of T2DM might be related to AEPSa regulating the gut microbiota against the TLR4/NF-κB pathway to protect the intestinal barrier. Therefore, AEPSa might be developed as a prebiotic agent against T2DM by regulating gut microbiota.}, } @article {pmid36639024, year = {2023}, author = {Li, HY and Huang, SY and Zhou, DD and Xiong, RG and Luo, M and Saimaiti Data Acquisition, A and Han, MK and Gan, RY and Zhu, HL and Li, HB}, title = {Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2023.01.008}, pmid = {36639024}, issn = {2090-1224}, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.

OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.

METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.

RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.

CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.}, } @article {pmid36638854, year = {2023}, author = {Guo, HH and Shen, HR and Tang, MZ and Sheng, N and Ding, X and Lin, Y and Zhang, JL and Jiang, JD and Gao, TL and Wang, LL and Han, YX}, title = {Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {116158}, doi = {10.1016/j.jep.2023.116158}, pmid = {36638854}, issn = {1872-7573}, abstract = {Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear.

AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases.

MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored.

RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia.

CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.}, } @article {pmid36638713, year = {2023}, author = {Wang, Z and Sun, Y and Han, Y and Chen, X and Gong, P and Zhai, P and Yao, W and Ba, Q and Wang, H}, title = {Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {110}, number = {}, pages = {154652}, doi = {10.1016/j.phymed.2023.154652}, pmid = {36638713}, issn = {1618-095X}, abstract = {BACKGROUND: The bark of Eucommia ulmoides (a perennial deciduous tree termed eucommia hereafter) has anti-hyperlipidemia effects due to its bioactive components. However, the slow growth of eucommia bark leads to a deficit in this resource. Studies have shown that eucommia leaf has bioactive components similar to those of eucommia bark and anti-hyperlipidemia effects. At present, the strength of the anti-hyperlipidemia effect of eucommia bark and eucommia leaf has not been reported. Their interaction with the gut microbiota and the mechanism by which the gut microbiota exerts anti-hyperlipidemia effects are unclear.

PURPOSES: Through fecal microbiota transplantation (FMT) experiments, this study aimed to investigate the mechanism by which fecal bacteria suspensions containing chlorogenic acid (CGA), eucommia bark extract (EBE), and eucommia leaves extract (ELE) improve high-fat diet (HFD)-induced lipid metabolism disorders. Difference in anti-hyperlipidemia effects between EBE and ELE and exploring an eucommia bark substitute to improve the sustainable utilization of eucommia were also evaluated.

RESULTS: EBE and ELE contain eight identical bioactive ingredients, and fecal bacteria suspensions containing EBE and ELE significantly improved HFD-induced lipid metabolism disorders and elevated blood glucose levels. The fecal bacteria suspension of healthy mice containing CGA, EBE, and ELE significantly reduced the relative abundance of Erysipelothrichaceae and Ruminococcaceae and promoted short chain fatty acids (SCFAs) production thereby activating the expression of the SCFA. G protein-coupled receptor 43 (GPR43) gene in colon and epididymal fat tissues. In addition, fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE significantly activated fasting-induced adipose factor (Fiaf) gene expression in colon tissue and inhibited the secretion of lipoprotein lipase (LPL) in liver tissue, thereby inhibiting the synthesis of triglycerides (TG). Changed in the Erysipelotrichaceae and Ruminococcaceae relative abundances were significantly correlated with these target genes. Thus, regulating the abundance of the Erysipelotrichaceae and Ruminococcaceae could serve as a potential target for the role of fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE in the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. In addition, regarding HFD-induced lipid metabolism disorders and gut microbiota structural disorders, we found no significant difference between ELE and EBE.

CONCLUSIONS: Our FMT experiments evidenced that EBE and ELE improve lipid metabolism disorders by regulating the gut microbiota, providing a new pathway for treating hyperlipidemia using eucommia dietary therapy. There was no significant difference in the anti-hyperlipidemia effects of ELE and EBE; thus, eucommia leaf could replace eucommia bark in traditional Chinese medicine, so as to achieve a sustainable utilization of eucommia resources.}, } @article {pmid36638348, year = {2023}, author = {Zeng, X and Li, X and Li, X and Wei, C and Shi, C and Hu, K and Kong, D and Luo, Q and Xu, Y and Shan, W and Zhang, M and Shi, J and Feng, J and Han, Y and Huang, H and Qian, P}, title = {Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2022017514}, pmid = {36638348}, issn = {1528-0020}, abstract = {Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has been recently reported to impact hematopoiesis. However, there is currently limited empirical evidence elucidating the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Further, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated FoxO signaling pathway and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota construction and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.}, } @article {pmid36637229, year = {2023}, author = {Green, JE and Berk, M and Mohebbi, M and Loughman, A and McGuinness, AJ and Castle, D and Chatterton, ML and Perez, J and Strandwitz, P and Athan, E and Hair, C and Nierenberg, AA and Cryan, JF and Jacka, F}, title = {Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437221150508}, doi = {10.1177/07067437221150508}, pmid = {36637229}, issn = {1497-0015}, abstract = {OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD.

METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD.

RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD.

CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.}, } @article {pmid36636378, year = {2023}, author = {Guan, X and Sun, Z}, title = {The Role of Intestinal Flora and Its Metabolites in Heart Failure.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {51-64}, pmid = {36636378}, issn = {1178-6973}, abstract = {Intestinal flora is a complex collection of microbial communities that participate in the physiological and pathological activities of the human body through various pathways. In recent years, numerous studies have reported that intestinal flora are involved in the occurrence and development of heart failure (HF) and its metabolic products could play an important role in this progression, suggesting a great value in the clinical treatment of this condition. This study reported the interaction between intestinal flora and HF, and with intestinal flora metabolites, such as short-chain fatty acids, trimethylamine N-oxide and bile acids and urotoxins, considered as the starting point, the mechanism of the roles in HF was summarized. Additionally, the current research status and the development prospects of applying flora and metabolites to the clinical therapeutic decision of HF were discussed.}, } @article {pmid36631533, year = {2023}, author = {Shrode, RL and Knobbe, JE and Cady, N and Yadav, M and Hoang, J and Cherwin, C and Curry, M and Garje, R and Vikas, P and Sugg, S and Phadke, S and Filardo, E and Mangalam, AK}, title = {Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {526}, pmid = {36631533}, issn = {2045-2322}, support = {T32 GM139776/NH/NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; Female ; *Breast Neoplasms ; Dysbiosis/microbiology ; Bacteria/genetics ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics/analysis ; }, abstract = {As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.}, } @article {pmid36632334, year = {2022}, author = {Wexler, A}, title = {Mapping the Landscape of Do-it-Yourself Medicine.}, journal = {Citizen science : theory and practice}, volume = {7}, number = {1}, pages = {}, pmid = {36632334}, issn = {2057-4991}, abstract = {The practice of medicine is typically conceptualized as remaining within the boundaries of a hospital or clinic. However, in recent years, patients have been able to gain access to information about medical research as it is ongoing. As a result, there has been a rise in do-it-yourself (DIY) medicine, where individuals treat themselves for medical conditions outside of clinical settings, often mimicking experimental therapies that remain inaccessible to the wider public. For example, in DIY brain stimulation, individuals suffering from depression build at-home electrical headsets using nine-volt batteries, mimicking an experimental neuroscience technique used in scientific laboratories. In DIY fecal transplantation, those with intestinal disorders like C. Difficile and inflammatory bowel disease transplant stool from donors into themselves with the aid of blenders and enemas. In the open Artificial Pancreas System movement, diabetes patients hacked together an artificial pancreas system from their glucose monitors and insulin pumps, years before such a system was approved by the United States Food and Drug Administration (US FDA). To date, scholarship on DIY medicine has largely been relegated to specific medical domains (e.g., neurology, gastroenterology, infectious disease). In this paper, however, I recognize DIY medicine as a cross-cutting phenomenon that has emerged independently across medical domains but shares common features. I map the varieties of DIY medicine across these domains and suggest that four key factors lead to their creation, growth, and uptake. In doing so, this essay sheds light on an understudied area of biomedical citizen science that is likely to grow substantially in the coming decades.}, } @article {pmid36632246, year = {2022}, author = {Patel, M and Atluri, LM and Gonzalez, NA and Sakhamuri, N and Athiyaman, S and Randhi, B and Gutlapalli, SD and Pu, J and Zaidi, MF and Khan, S}, title = {A Systematic Review of Mixed Studies Exploring the Effects of Probiotics on Gut-Microbiome to Modulate Therapy in Children With Autism Spectrum Disorder.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32313}, pmid = {36632246}, issn = {2168-8184}, abstract = {Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder characterized by social deficits, repetitive typical behaviors, insistence on the same routines, and communication impairments. The prevalence of ASD has increased in the past decade. While we are aware that there is no cure for ASD, attempts are being made to reduce its symptoms and improve the learning, overall growth, and well-being of ASD patients. Gastrointestinal (GI) symptoms are frequent occurrences in patients with ASD, but the underlying mechanisms are unknown. Recent studies show that the microbiota-gut-brain axis is the key modulator of neuropsychiatric health. Although fecal transplants have shown positive outcomes in treating dysbiosis and symptoms of autism, lifestyle modifications such as dietary intervention will prevent and treat this disorder without causing major adverse effects. Probiotics enhance the microbiome to provide necessary metabolites, which help in gut permeability, cognitive function, and immunity. In some studies, children with increased GI symptoms have also shown increased behavioral disturbances. In this study, a systematic review of mixed studies is conducted to obtain more robust and conclusive results. We included randomized