@article {pmid38033573, year = {2023}, author = {Zhu, Q and Wu, K and Yang, Q and Meng, B and Niu, Y and Zhao, F}, title = {Advances in psoriasis and gut microorganisms with co-metabolites.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1192543}, pmid = {38033573}, issn = {1664-302X}, abstract = {This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.}, } @article {pmid38033557, year = {2023}, author = {Xiang, W and Xiang, H and Wang, J and Jiang, Y and Pan, C and Ji, B and Zhang, A}, title = {Fecal microbiota transplantation: a novel strategy for treating Alzheimer's disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281233}, pmid = {38033557}, issn = {1664-302X}, abstract = {Alzheimer's disease is a common neurological disorder, which has become one of the major factors affecting human health due to its serious impact on individuals, families and society. It has been confirmed that gut microbiota can affect the occurrence and development of Alzheimer's disease. Especially, fecal microbiota transplantation plays a positive role in the treatment of Alzheimer's disease. The mechanisms for improving Alzheimer's disease might include anti-inflammation and regulation of amyloid β-protein, synaptic plasticity, short-chain fatty acids, and histone acetylation. In this mini-review, the relationship between fecal microbiota transplantation and Alzheimer's disease was summarized. It is hoped that fecal microbiota transplantation would play a positive role in the prevention and treatment of Alzheimer's disease in the future.}, } @article {pmid38031252, year = {2023}, author = {Crossland, NA and Beck, S and Tan, WY and Lo, M and Mason, JB and Zhang, C and Guo, W and Crott, JW}, title = {Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2288187}, doi = {10.1080/19490976.2023.2288187}, pmid = {38031252}, issn = {1949-0984}, abstract = {Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.}, } @article {pmid38030980, year = {2023}, author = {Liu, H and Li, J and Yuan, J and Huang, J and Xu, Y}, title = {Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {371}, pmid = {38030980}, issn = {1471-2180}, abstract = {AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC).

METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs).

RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs.

CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.}, } @article {pmid38030463, year = {2023}, author = {Catalán, V and Gómez-Ambrosi, J}, title = {Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2023.11.025}, pmid = {38030463}, issn = {1879-0828}, } @article {pmid38030048, year = {2023}, author = {Gong, X and Ma, Y and Deng, X and Li, A and Li, X and Kong, X and Liu, Y and Liu, X and Guo, K and Yang, Y and Li, Z and Wei, H and Zhou, D and Hong, Z}, title = {Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2023.11.030}, pmid = {38030048}, issn = {1090-2139}, abstract = {Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.}, } @article {pmid38029942, year = {2023}, author = {Xie, Z and Zhou, J and Zhang, X and Li, Z}, title = {Clinical potential of microbiota in thyroid cancer therapy.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {2}, pages = {166971}, doi = {10.1016/j.bbadis.2023.166971}, pmid = {38029942}, issn = {1879-260X}, abstract = {Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing number of studies have identified a key role for the gut, thyroid tissue and oral microbiota in the regulation of metabolism and the immune system. A growing body of evidence has conclusively demonstrated that the microbiota influences tumor formation, prevention, diagnosis, and treatment. We provide extensive information in which oral, gut, and thyroid microbiota have an effect on thyroid cancer development in this review. In addition, we thoroughly discuss the various microbiota species, their potential functions, and the underlying mechanisms for thyroid cancer. The microbiome offers a unique opportunity to improve the effectiveness of immunotherapy and radioiodine therapy thyroid cancer by maintaining the right type of microbiota, and holds great promise for improving clinical outcomes and quality of life for thyroid cancer patients.}, } @article {pmid38029189, year = {2023}, author = {Zhang, X and Luo, X and Tian, L and Yue, P and Li, M and Liu, K and Zhu, D and Huang, C and Shi, Q and Yang, L and Xia, Z and Zhao, J and Ma, Z and Li, J and Leung, JW and Lin, Y and Yuan, J and Meng, W and Li, X and Chen, Y}, title = {The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1286429}, pmid = {38029189}, issn = {1664-302X}, abstract = {BACKGROUND: Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.

METHODS: The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).

RESULTS: Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases.

CONCLUSION: Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.}, } @article {pmid38025767, year = {2023}, author = {Sun, H and Su, X and Liu, Y and Li, G and Du, Q}, title = {Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats.}, journal = {iScience}, volume = {26}, number = {12}, pages = {108392}, pmid = {38025767}, issn = {2589-0042}, abstract = {Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.}, } @article {pmid38024855, year = {2023}, author = {Mao, Z and Hui, H and Zhao, X and Xu, L and Qi, Y and Yin, L and Qu, L and Han, L and Peng, J}, title = {Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling.}, journal = {Journal of pharmaceutical analysis}, volume = {13}, number = {10}, pages = {1153-1167}, pmid = {38024855}, issn = {2214-0883}, abstract = {It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.}, } @article {pmid38024475, year = {2023}, author = {Zhao, W and Lei, J and Ke, S and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Alnaggar, M and Qiu, H and Shi, W and Yin, L and Chen, Y}, title = {Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).}, journal = {EClinicalMedicine}, volume = {66}, number = {}, pages = {102315}, pmid = {38024475}, issn = {2589-5370}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC.

METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768.

FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders.

INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population.

FUNDING: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).}, } @article {pmid38022314, year = {2023}, author = {Sharifa, M and Ghosh, T and Daher, OA and Bhusal, P and Alaameri, YA and Naz, J and Ekhator, C and Bellegarde, SB and Bisharat, P and Vaghani, V and Hussain, A}, title = {Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47058}, doi = {10.7759/cureus.47058}, pmid = {38022314}, issn = {2168-8184}, abstract = {This comprehensive review delves into the intricate relationship between the gut microbiota and multiple sclerosis (MS), shedding light on the potential therapeutic avenues for this complex autoimmune disease. It emphasizes the multifactorial nature of MS, including genetic, environmental, and gender-related factors. Furthermore, the article highlights the emerging role of gut microbiota in MS pathophysiology, particularly in terms of gut dysbiosis, oxidative stress, and inflammasome activation within the gut-brain axis. This interplay raises intriguing questions about how the gut microbiota influences the onset and progression of MS. Environmental factors, such as diet and pollutants, add further layers of complexity to the connection between gut health and MS risk. This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition.}, } @article {pmid38021361, year = {2023}, author = {Sehgal, K and Feuerstadt, P}, title = {The real efficacy of microbiota restoration following standard of care antimicrobial in patients with recurrent Clostridiodes difficile.}, journal = {Translational gastroenterology and hepatology}, volume = {8}, number = {}, pages = {31}, doi = {10.21037/tgh-23-46}, pmid = {38021361}, issn = {2415-1289}, } @article {pmid38018424, year = {2023}, author = {Hu, S and Zhao, R and Xu, Y and Gu, Z and Zhu, B and Hu, J}, title = {Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances.}, journal = {Journal of materials chemistry. B}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3tb02302h}, pmid = {38018424}, issn = {2050-7518}, abstract = {Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.}, } @article {pmid38018317, year = {2023}, author = {Xiao, Y and Feng, J and Jia, J and Li, J and Zhou, Y and Song, Z and Guan, F and Li, X and Liu, L}, title = {Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcsm.13379}, pmid = {38018317}, issn = {2190-6009}, support = {2022YFS0632//Sichuan Provincial Science and Technology Plan Joint Innovation Projects/ ; }, abstract = {BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.

METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.

RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.

CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.}, } @article {pmid38016701, year = {2023}, author = {Lin, J and Xiong, J and Jin, Y and Wang, H and Wu, L and Chen, L and Zhang, F and Ji, G and Cui, B}, title = {Fecal microbiota transplantation through transendoscopic enteral tubing for inflammatory bowel disease: High acceptance and high satisfaction.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16435}, pmid = {38016701}, issn = {1440-1746}, support = {BK20211384//Nature Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD.

METHODS: A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients.

RESULTS: The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost.

CONCLUSIONS: TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.}, } @article {pmid38016505, year = {2023}, author = {Li, S and Chen, T and Zhou, Y and Li, X}, title = {Palmitic acid and trans-4-hydroxy-3-methoxycinnamate, the active ingredients of Yaobishu formula, reduce inflammation and pain by regulating gut microbiota and metabolic changes after lumbar disc herniation to activate autophagy and the Wnt/β-catenin pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {166972}, doi = {10.1016/j.bbadis.2023.166972}, pmid = {38016505}, issn = {1879-260X}, abstract = {The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.}, } @article {pmid38016344, year = {2023}, author = {Wu, Y and Zhang, Y and Xie, B and Zhang, X and Wang, G and Yuan, S}, title = {Esketamine mitigates cognitive impairment following exposure to LPS by modulating the intestinal flora/subdiaphragmatic vagus nerve/spleen axis.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111284}, doi = {10.1016/j.intimp.2023.111284}, pmid = {38016344}, issn = {1878-1705}, abstract = {INTRODUCTION: Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the underlying mechanisms are not yet fully elucidated.

OBJECTIVE: To investigate whether esketamine treatment immediately after primary lipopolysaccharide (LPS) exposure could alleviate cognitive impairment caused by secondary infection.

METHODS: Mice were injected intraperitoneally (IP) with LPS (5 mg/kg) 10 days apart. Esketamine (10, 15, or 30 mg/kg) was administered IP immediately after the primary LPS injection. Splenectomy or subdiaphragmatic vagotomy (SDV) was performed 7 days before secondary LPS exposure or broad-spectrum antibiotic administration.

RESULTS: Splenomegaly was observed after the primary LPS injection on Days 3 and 10. Splenomegaly was attenuated by treatment with 30 mg/kg esketamine. Esketamine treatment prevented increased plasma proinflammatory cytokines levels and cognitive dysfunction induced by secondary LPS exposure. Mice that underwent splenectomy or SDV had lower proinflammatory cytokines levels, higher hippocampal brain-derived neurotrophic factor (BDNF) levels, and improved cognitive function 1 day after secondary infection, which was not further improved by esketamine. Fecal microbiota transplantation (FMT) from endotoxic mice treated with esketamine attenuated hippocampal BDNF downregulation and cognitive dysfunction only in pseudo germ-free (PGF) mice without splenectomy. FMT with fecal suspensions from esketamine-treated endotoxic mice abrogated splenomegaly only in PGF mice without SDV. Blocking BDNF signaling blocked esketamine's ameliorating effects on secondary LPS exposure-induced cognitive dysfunction.

CONCLUSION: The intestinal flora/subdiaphragmatic vagus nerve/spleen axis-mediated hippocampal BDNF downregulation significantly affected secondary LPS-induced systemic inflammation and cognitive dysfunction. Esketamine preserves cognitive function via this mechanism.}, } @article {pmid38015634, year = {2023}, author = {Gurczynski, SJ and Lipinski, JH and Strauss, JY and Alam, S and Huffnagle, GB and Ranjan, P and Kennedy, LH and Moore, BB and O'Dwyer, DN}, title = {Horizontal transmission of gut microbiota attenuates mortality in lung fibrosis.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.164572}, pmid = {38015634}, issn = {2379-3708}, abstract = {Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma resulting in loss of physiological homeostasis, respiratory failure and death. The immune response in pulmonary fibrosis is dysregulated. The gut microbiome is a key regulator of immunity. The role of the gut microbiome in regulating the pulmonary immunity in lung fibrosis is poorly understood. Here, we determine the impact of gut microbiota on pulmonary fibrosis in C57BL/6 mice derived from different vendors (C57BL/6J and C57BL/6NCrl). We use germ free models, fecal microbiota transplantation and cohousing to transmit gut microbiota. Metagenomic studies of feces establish keystone species between sub-strains. Pulmonary fibrosis is microbiota dependent in C57BL/6 mice. Gut microbiota are distinct by β diversity (PERMANOVA P<0.001) and α diversity (P<0.0001). Mortality and lung fibrosis are attenuated in C57BL/6NCrl mice. Elevated CD4+ IL-10+ T cells and lower IL-6 occur in C57BL/6NCrl mice. Horizontal transmission of microbiota by cohousing attenuates mortality in C57BL/6J mice and promotes a transcriptionally altered pulmonary immunity. Temporal changes in lung and gut microbiota demonstrates that gut microbiota contribute largely to immunological phenotype. Key regulatory gut microbiota contribute to lung fibrosis generating rationale for human studies.}, } @article {pmid38015106, year = {2023}, author = {Sun, L and Li, Z and Hu, C and Ding, J and Zhou, Q and Pang, G and Wu, Z and Yang, R and Li, S and Li, J and Cai, J and Sun, Y and Li, R and Zhen, H and Sun, S and Zhang, J and Fang, M and Chen, Z and Lv, Y and Cao, Q and Sun, Y and Gong, R and Huang, Z and Duan, Y and Liu, H and Dong, J and Li, J and Ruan, J and Lu, H and He, B and Li, N and Li, T and Xue, W and Li, Y and Shen, J and Yang, F and Zhao, C and Liang, Q and Zhang, M and Chen, C and Gong, H and Hou, Y and Wang, J and Zhang, Y and Yang, H and Zhu, S and Xiao, L and Jin, Z and Guo, H and Zhao, P and Brix, S and Xu, X and Jia, H and Kristiansen, K and Yang, Z and Nie, C}, title = {Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14028}, doi = {10.1111/acel.14028}, pmid = {38015106}, issn = {1474-9726}, support = {U23A20470//National Scientific Foundation of P. R. China/ ; 82260289//National Scientific Foundation of P. R. China/ ; 91849132//National Scientific Foundation of P. R. China/ ; 81571385//National Scientific Foundation of P. R. China/ ; BJ-2018-139//Beijing Hospital Nova Project/ ; 2021-I2M-1-050//CAMS Innovation Fund for Medical Sciences/ ; 2021YFE0111800//National Key Research and Development Program of China/ ; 2023YFC3603300//National Key Research and Development Program of China/ ; 2018YFC2000400//National Key Research and Development Program of China/ ; 202001AY070001-011//The Priority Union Foundation of Yunnan Provincial Science and Technology Department/ ; BJ-2023-168//National High Level Hospital Clinical Research Funding/ ; BJ-2023-075//National High Level Hospital Clinical Research Funding/ ; 2022ZD0211600//Science and Technology lnnovation 2030 Major Projects/ ; }, abstract = {Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.}, } @article {pmid38014241, year = {2023}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early life programming of gastrointestinal motility.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.08.566304}, pmid = {38014241}, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.}, } @article {pmid38012646, year = {2023}, author = {Kim, N and Ju, IG and Jeon, SH and Lee, Y and Jung, MJ and Gee, MS and Cho, JS and Inn, KS and Garrett-Sinha, LA and Oh, MS and Lee, JK}, title = {Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {282}, pmid = {38012646}, issn = {1742-2094}, support = {NRF-2022R1A6A3A01087341//National Research Foundation of Korea/ ; NRF-2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Mice ; Animals ; *Alzheimer Disease/pathology ; Microglia/metabolism ; M Cells ; Neuroinflammatory Diseases ; Amyloid beta-Peptides/metabolism ; Memory Disorders ; Mice, Knockout ; Phenotype ; Disease Models, Animal ; Mice, Transgenic ; }, abstract = {BACKGROUND: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.

METHODS: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.

RESULTS: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib[-/-] mice.

CONCLUSION: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.}, } @article {pmid38012463, year = {2023}, author = {Hart, NH and Wallen, MP and Farley, MJ and Haywood, D and Boytar, AN and Secombe, K and Joseph, R and Chan, RJ and Kenkhuis, MF and Buffart, LM and Skinner, TL and Wardill, HR}, title = {Exercise and the gut microbiome: implications for supportive care in cancer.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {31}, number = {12}, pages = {724}, pmid = {38012463}, issn = {1433-7339}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Exercise/physiology ; *Neoplasms/therapy ; Diet ; *Sports ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population.

METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors.

RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists.

CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.}, } @article {pmid38011635, year = {2023}, author = {Choueiry, F and Gold, A and Xu, R and Zhang, S and Zhu, J}, title = {Secondary-Electrospray Ionization Mass Spectrometry-Based Online Analyses of Mouse Volatilome Uncover Gut Microbiome-Dictated Metabolic Changes in the Host.}, journal = {Journal of the American Society for Mass Spectrometry}, volume = {}, number = {}, pages = {}, doi = {10.1021/jasms.3c00304}, pmid = {38011635}, issn = {1879-1123}, abstract = {The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism. Herein, we report that microbial-mediated metabolic influences can alter the host volatilome and the prominent volatile changes can be uncovered by a novel volatile analysis technique named secondary electrospray ionization mass spectrometry. Mice were subjected to an antibiotic cocktail to deplete the microbiome and then inoculated with either single strain bacteria or fecal matter transplantation (FMT) to replete the microbial population in the gut. VOC sampling was achieved by using an advanced secondary electrospray ionization (SESI) source that directly mounted onto a Thermo Q-Exactive high-resolution mass spectrometer (HRMS). A principal component analysis summarizing the volatile profiles of the mice revealed independent clustering of each strain of the FMT-inoculated groups, suggesting unique volatile profiles. The Mummichog algorithm uncovered phenylalanine metabolism as a significantly altered metabolic profile in the volatilome of the microbiome-repleted mice. Our results indicated that the systemic metabolic changes incurred by the host are translated to unique volatile profiles correlated to the diversity of the microbial population colonized within the host. It is thus possible to take advantage of SESI-HRMS-based platforms for noninvasive screening of VOCs to determine the contribution of various microbial colonization within human gut that may impact host health.}, } @article {pmid38010914, year = {2023}, author = {Liang, D and Liu, H and Jin, R and Feng, R and Wang, J and Qin, C and Zhang, R and Chen, Y and Zhang, J and Teng, J and Tang, B and Ding, X and Wang, X}, title = {Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276296}, doi = {10.1080/19490976.2023.2276296}, pmid = {38010914}, issn = {1949-0984}, abstract = {Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of LRRK2 risk variants are still unknown. Here, we report that a markedly increased abundance of Escherichia coli (E. coli) in the intestinal microbiota was detected in LRRK2 risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that E. coli administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in Lrrk2 R1628P mice, due to the co-occurrence of Lrrk2 variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in E. coli-derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in Lrrk2 R1628P mice. Our findings elaborate on the mechanism that E. coli triggers α-syn pathology in Lrrk2 R1628P mice, and highlight a novel gene-environment interaction pattern in LRRK2 risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.}, } @article {pmid38010886, year = {2023}, author = {Garrett, S and Asada, MC and Sun, J}, title = {Axin1's mystique in manipulating microbiome amidst colitis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2286674}, doi = {10.1080/19490976.2023.2286674}, pmid = {38010886}, issn = {1949-0984}, abstract = {Classically, Axin1 is considered a regulator of Wnt/β-catenin signaling. However, Axin1's roles in host-microbial interactions have been unknown. Our recent study has demonstrated that deletion of intestinal epithelial Axin1 in epithelial cells and Paneth cells protects the host against colitis by enhancing Akkermansia muciniphila. Loss of intestinal epithelial or Paneth cell Axin1 results in increased Wnt/β-catenin signaling, proliferation, and cell migration. This is associated with morphologically altered goblet and Paneth cells, including increased Muc2 and decreased lysozyme. Axin1 deletion specifically enriched Akkermansia muciniphila. Akkermansia muciniphila in Axin1 knockout mice is the driver of protection against DSS-induced inflammation. Here, we feature several significant conceptual changes, such as differences between Axin1 and Axin2, Axin1 in innate immunity and microbial homeostasis, and Axin1 reduction of Akkermansia muciniphila. We discuss an important trend in the field related to Paneth cells and tissue-specific Axin1 manipulation of microbiome in health and inflammation.}, } @article {pmid38010872, year = {2023}, author = {Ahmad, R and Kumar, B and Thapa, I and Talmon, GA and Salomon, J and Ramer-Tait, AE and Bastola, DK and Dhawan, P and Singh, AB}, title = {Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282789}, doi = {10.1080/19490976.2023.2282789}, pmid = {38010872}, issn = {1949-0984}, abstract = {Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.}, } @article {pmid38010168, year = {2023}, author = {Ye, H and Ghosh, TS and Hueston, CM and Vlckova, K and Golubeva, AV and Hyland, NP and O'Toole, PW}, title = {Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282796}, doi = {10.1080/19490976.2023.2282796}, pmid = {38010168}, issn = {1949-0984}, abstract = {Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.}, } @article {pmid38009301, year = {2023}, author = {Xiong, Y and He, Y and Chen, Z and Wu, T and Xiong, Y and Peng, Y and Yang, X and Liu, Y and Zhou, J and Zhou, H and Zhang, W and Shu, Y and Li, X and Li, Q}, title = {Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.}, journal = {Journal of hypertension}, volume = {}, number = {}, pages = {}, doi = {10.1097/HJH.0000000000003613}, pmid = {38009301}, issn = {1473-5598}, abstract = {OBJECTIVE: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect.

METHODS: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).

RESULTS: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus, and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii (L. johnsonii) and Lactobacillus reuteri (L. reuteri) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii, and L. reuteri can significantly increase SCFA content in SHR feces.

CONCLUSION: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus.}, } @article {pmid38009195, year = {2023}, author = {Hu, S and Zhou, J and Hao, J and Zhong, Z and Wu, H and Zhang, P and Yang, J and Guo, H and Chi, J}, title = {Emodin ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through the remodeling of gut microbiota composition.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00477.2023}, pmid = {38009195}, issn = {1522-1563}, support = {No. 82174204//MOST | National Natural Science Foundation of China (NSFC)/ ; No. 81873120//MOST | National Natural Science Foundation of China (NSFC)/ ; }, abstract = {The relationship between gut microbiota and doxorubicin-induced cardiotoxicity (DIC) is becoming increasingly clear. Emodin (EMO), a naturally occurring anthraquinone, exerts cardioprotective effects and plays a protective role by regulating gut microbiota composition. Therefore, the protective effect of EMO against DIC injury and its underlying mechanisms are worth investigating. In this study, we analyzed the differences in the gut microbiota in recipient mice transplanted with different flora using 16S-rDNA sequencing, analyzed the differences in serum metabolites among groups of mice using a non-targeted gas chromatography-mass spectrometry coupling system, and assessed cardiac function based on cardiac morphological staining, cardiac injury markers, and ferroptosis indicator assays. We found EMO ameliorated DIC and ferroptosis, as evidenced by decreased myocardial fibrosis, cardiomyocyte hypertrophy, and myocardial disorganization; improved ferroptosis indicators; and the maintenance of normal mitochondrial morphology. The protective effect of EMO was eliminated by the scavenging effect of antibiotics on the gut microbiota. Through fecal microbiota transplantation (FMT), we found that EMO restored the gut microbiota disrupted by doxorubicin (DOX) to near-normal levels. This was evidenced by an increased proportion of Bacteroidota and a decreased proportion of Verrucomicrobiota. FMT resulted in changes in the composition of serum metabolites. Mice transplanted with EMO-improved gut microbiota showed better cardiac function and ferroptosis indices; however, these beneficial effects were not observed in Nrf2[-/-] mice. Overall, EMO exerted a protective effect against DIC by attenuating ferroptosis, and the above effects occurred by remodeling the composition of gut microbiota perturbed by DOX and required Nrf2 mediation.}, } @article {pmid38007451, year = {2023}, author = {Ma, J and Zhou, M and Song, Z and Deng, Y and Xia, S and Li, Y and Huang, X and Xiao, D and Yin, Y and Yin, J}, title = {Clec7a drives gut fungus-mediated host lipid deposition.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {264}, pmid = {38007451}, issn = {2049-2618}, support = {2022YFD1301500//National Key Research and Development Program of China/ ; 32172761//National Natural Science Foundation of China/ ; CARS-37//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {Humans ; Animals ; Mice ; Swine ; *Antifungal Agents ; *Obesity/metabolism ; Diet, High-Fat/adverse effects ; Lipids ; Fungi ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Compared to that of bacteria, the role of gut fungi in obesity development remains unknown.

RESULTS: Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi.

CONCLUSIONS: Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract.}, } @article {pmid38004817, year = {2023}, author = {Parigi, TL and Vieujean, S and Paridaens, K and Dalgaard, K and Peyrin-Biroulet, L and Danese, S}, title = {Efficacy, Safety, and Concerns on Microbiota Modulation, Antibiotics, Probiotics, and Fecal Microbial Transplant for Inflammatory Bowel Disease and Other Gastrointestinal Conditions: Results from an International Survey.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004817}, issn = {2076-2607}, abstract = {The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.}, } @article {pmid38004765, year = {2023}, author = {Salandre, A and Delannoy, J and Goudiaby, MTB and Barbut, F and Thomas, M and Waligora-Dupriet, AJ and Kapel, N}, title = {A Simple In Vitro Test to Select Stools for Fecal Microbiota Transplantation to Limit Intestinal Carriage of Extensively Drug-Resistant Bacteria.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004765}, issn = {2076-2607}, abstract = {Treatment options for multidrug-resistant bacterial infections are limited and often ineffective. Fecal microbiota transplantation (FMT) has emerged as a promising therapy for intestinal multidrug-resistant bacterial decolonization. However, clinical results are discrepant. The aim of our pilot study was to evaluate the screening performance of a simple diagnostic tool to select fecal samples that will be effective in decolonizing the intestine. Fecal samples from 10 healthy subjects were selected. We developed an agar spot test to evaluate their antagonistic activity toward the growth of VanA Enterococcus faecium and OXA-48-producing Klebsiella pneumoniae, two of the most serious and urgent threats of antibiotic resistance. Most fecal samples were able to limit the growth of both bacteria in vitro but with large inter-individual variation. The samples with the highest and lowest antagonistic activity were used for FMT in a mouse model of intestinal colonization. FMT was not successful in reducing intestinal colonization with VanA Enterococcus faecium, whereas FMT performed with the fecal sample showing the highest activity on the agar spot test was able to significantly reduce the intestinal colonization of mice with Klebsiella pneumoniae OXA-48. The agar spot test could thus serve as a reliable screening tool to select stool samples with the best potential to eradicate/reduce multidrug-resistant bacteria carriage after FMT.}, } @article {pmid38004758, year = {2023}, author = {Yan, P and Luo, S and Guo, L and Wang, X and Ren, X and Lv, J and Chen, Y and Lin, X and Chen, J and Wang, R}, title = {Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004758}, issn = {2076-2607}, support = {82070766//National Natural Science Foundation of China/ ; 2022RC147//Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; LQ23H050003//Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.}, } @article {pmid38004180, year = {2023}, author = {Zhou, J and Ho, V}, title = {Role of Baseline Gut Microbiota on Response to Fiber Intervention in Individuals with Irritable Bowel Syndrome.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004180}, issn = {2072-6643}, support = {Investigator Initiated Funding Scheme//Nestlé Foundation/ ; }, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; *Gastrointestinal Microbiome/physiology ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual's baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual's baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.}, } @article {pmid38004128, year = {2023}, author = {He, S and Lin, F and Hu, X and Pan, P}, title = {Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients-A Narrative Review.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004128}, issn = {2072-6643}, support = {z047-02//The national key clinical specialist construction programs of China/ ; }, mesh = {Humans ; Adult ; *Gastrointestinal Microbiome/physiology ; Critical Illness/therapy ; *Microbiota/physiology ; Fecal Microbiota Transplantation/adverse effects ; Prognosis ; Dysbiosis/therapy/etiology ; }, abstract = {The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.}, } @article {pmid38002138, year = {2023}, author = {Xiao, N and Ruan, S and Mo, Q and Zhao, M and Feng, F}, title = {The Effect of Sodium Benzoate on Host Health: Insight into Physiological Indexes and Gut Microbiota.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {22}, pages = {}, pmid = {38002138}, issn = {2304-8158}, support = {32072224,32001693 and 32172214//National Natural Science Foundation of China/ ; LD19C200001and LQ21C200007//Zhejiang Provincial Natural Science Foundation/ ; }, abstract = {Sodium benzoate (SB) is a common food preservative widely used in the food industry. However, the effects of SB intake on host health at different stages were still unclear. Hence, we investigated the impact of SB with three concentrations (150 mg/kg, 500 mg/kg and 1000 mg/kg) and at three stages (intake for 5-weeks, intake for 10-weeks and removal for 5 weeks) on host health in normal mice. The results showed that SB intake for 5 weeks slightly changed gut microbiota composition, but it significantly increased TG (only 150 mg/kg and 1000 mg/kg) and blood glucose levels (only 500 mg/kg) and promoted the secretion of interleukin (IL)-1β and IL-6 (p < 0.01). However, SB intake for 10 weeks mostly maintained normal glucolipid metabolism; although, IL-1β (p < 0.01) and IL-6 (p < 0.05) levels were also significantly increased and positively regulated the gut microbiota by significantly increasing the relative abundance of Lactobacillus and significantly decreasing the relative abundance of Ileibacterium. Meanwhile, the safety of SB for host metabolism and gut microbiota was also confirmed via a fecal microbiota transplantation experiment. In addition, we found that SB removal after 10 weeks of intake significantly increased the levels of blood glucose, insulin and HOMA-IR index, which might be attributed to gut microbiota dysbiosis. Mechanistically, these positive effects and negative effects had no close relationship with the concentration of short-chain fatty acids in the gut, which might be associated with metabolites of SB or special bacterial strains. In short, this work provided positive evidence for the safety of SB consumption within the recommended range.}, } @article {pmid38001930, year = {2023}, author = {Boicean, A and Birlutiu, V and Ichim, C and Brusnic, O and Onișor, DM}, title = {Fecal Microbiota Transplantation in Liver Cirrhosis.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001930}, issn = {2227-9059}, abstract = {The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.}, } @article {pmid38001551, year = {2023}, author = {Xu, H and Fang, F and Wu, K and Song, J and Li, Y and Lu, X and Liu, J and Zhou, L and Yu, W and Yu, F and Gao, J}, title = {Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {262}, pmid = {38001551}, issn = {2049-2618}, support = {32001696//National Natural Science Foundation of China/ ; 2021AC19445//Specific Research Project of Guangxi for Research Bases and Talents/ ; }, mesh = {Mice ; Animals ; *Bile Acids and Salts/metabolism ; Lipid Metabolism ; *Gastrointestinal Microbiome/physiology ; Liver/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.

RESULTS: We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.

CONCLUSIONS: Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.}, } @article {pmid38001323, year = {2023}, author = {Yang, Y and Yan, J and Li, S and Liu, M and Han, R and Wang, Y and Wang, Z and Wang, D}, title = {Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.}, journal = {Endocrine}, volume = {}, number = {}, pages = {}, pmid = {38001323}, issn = {1559-0100}, support = {(No.[2020] No.23)//Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No.: [2020] No.23);/ ; (No.[2020] No.23)//Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No.: [2020] No.23);/ ; }, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM.

METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated.

RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes.

CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.}, } @article {pmid38000189, year = {2023}, author = {de-Mendoza, C and Pérez, L and Rando, A and Reina, G and Aguilera, A and Benito, R and Eirós, JM and Rodríguez-Avial, I and Ortega, D and Pozuelo, MJ and Pena, MJ and Soriano, V and , }, title = {HTLV-1-associated myelopathy in Spain.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {169}, number = {}, pages = {105619}, doi = {10.1016/j.jcv.2023.105619}, pmid = {38000189}, issn = {1873-5967}, abstract = {BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.

METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.

RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10[4] PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.

CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.}, } @article {pmid37999101, year = {2023}, author = {Duttagupta, S and Hakozaki, T and Routy, B and Messaoudene, M}, title = {The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer.}, journal = {Current oncology (Toronto, Ont.)}, volume = {30}, number = {11}, pages = {9406-9427}, pmid = {37999101}, issn = {1718-7729}, abstract = {The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients.}, } @article {pmid37998819, year = {2023}, author = {DuPont, HL and Salge, MMH}, title = {The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998819}, issn = {2079-6382}, abstract = {BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.

CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.}, } @article {pmid37996087, year = {2023}, author = {Chen, YF and Li, SC and Huang, EY}, title = {Role of microbiota in radiation-induced small-bowel damage.}, journal = {Journal of radiation research}, volume = {}, number = {}, pages = {}, doi = {10.1093/jrr/rrad084}, pmid = {37996087}, issn = {1349-9157}, support = {CORPG8K0161//Kaohsiung Chang Gung Medical Research Project/ ; }, abstract = {Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.}, } @article {pmid37995723, year = {2023}, author = {Distante, M and Rotulo, S and Ranalli, M and Pedace, E and Lionetti, P and Arrigo, S and Alvisi, P and Miele, E and Martinelli, M and Zuin, G and Bramuzzo, M and Cananzi, M and Aloi, M and , }, title = {Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izad275}, pmid = {37995723}, issn = {1536-4844}, abstract = {BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD).

METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults.

RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02).

CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.}, } @article {pmid37993541, year = {2023}, author = {Li, Z and Zhang, X and Wu, H and Ma, Z and Liu, X and Ma, J and Zhang, D and Sheng, L and Chen, X and Zhang, S}, title = {Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {1189}, pmid = {37993541}, issn = {2399-3642}, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome ; Coumarins/pharmacology ; *Hydrangea ; Dysbiosis ; *Endotoxemia ; *Nephritis ; }, abstract = {Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.}, } @article {pmid37992712, year = {2023}, author = {Zhang, C and Yu, L and Ma, C and Jiang, S and Zhang, Y and Wang, S and Tian, F and Xue, Y and Zhao, J and Zhang, H and Liu, L and Chen, W and Huang, S and Zhang, J and Zhai, Q}, title = {A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2023.10.011}, pmid = {37992712}, issn = {1934-6069}, abstract = {Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.}, } @article {pmid37992400, year = {2023}, author = {Qian, X and Hai, W and Chen, S and Zhang, M and Jiang, X and Tang, H}, title = {Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282790}, doi = {10.1080/19490976.2023.2282790}, pmid = {37992400}, issn = {1949-0984}, mesh = {Mice ; Animals ; Amyloid beta-Protein Precursor/genetics/metabolism ; Mice, Transgenic ; Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Multiomics ; Positron Emission Tomography Computed Tomography ; *Alzheimer Disease/complications ; Glycerophospholipids ; Disease Models, Animal ; }, abstract = {Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.}, } @article {pmid37992054, year = {2023}, author = {Zhang, M and Yang, T and Li, R and Ren, K and Li, J and He, M and Chen, J and Yi, SQ}, title = {Gut microbiota of Suncus murinus, a naturally obesity-resistant animal, improves the ecological diversity of the gut microbiota in high-fat-diet-induced obese mice.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0293213}, pmid = {37992054}, issn = {1932-6203}, mesh = {Humans ; Animals ; Mice ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Obese ; RNA, Ribosomal, 16S/genetics ; Ecosystem ; Mice, Inbred C57BL ; Obesity/etiology/therapy/metabolism ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: The global population of obese individuals is increasing, affecting human health. High-fat diets are a leading cause of this epidemic, and animal models, such as mice, are often used in related research. Obese individuals have a different gut microbiota composition from non-obese ones, characterized by a sizeable population of certain bacteria associated with fat storage. The gut microbiome plays a significant role in regulating human physiological and metabolic functions. Links between obesity, high-fat diets and gut microbiota have become hot topics of discussion. Recently, research on the modulation of the gut microbiota has focused on fecal microbiota transplantation (FMT), which has been recognized as an effective method of studying the function of gut microbiota.

OBJECTIVES: The purpose of this study was to investigate how the gut microbiota of Suncus murinus, a naturally obesity-resistant animal, through FMT, affected the ecology of the gut microbiota of high-fat diet induced obese mice.

METHODS: In this study, Suncus murinus was used as a donor for FMT. High-fat diet induced C57BL/6NCrSIc mice were used as recipients, the body weight changes were measured and changes in their gut flora were analyzed using a 16S rRNA gene analysis.

RESULTS: The study found that, after the FMT procedure, the FMT group tended to have a lower body weight than the control group. At the phylum level, the most predominant phyla in all groups were Firmicutes and Proteobacteria, while Deferribacteres was not detected in the FMT or antibiotic administration groups, and Bacteroidetes was not present in the antibiotic administration group. At the genus level, the FMT group had significantly lower OTU richness than the control group but greater diversity than the control group.

CONCLUSIONS: These results indicate that FMT from Suncus murinus can help reorganize and improve the gut microbiota of mice in a balanced and diverse ecosystem.}, } @article {pmid37990909, year = {2023}, author = {Boatman, S and Kaiser, T and Nalluri-Butz, H and Khan, MH and Dietz, M and Kohn, J and Johnson, AJ and Gaertner, WB and Staley, C and Jahansouz, C}, title = {Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2283147}, doi = {10.1080/19490976.2023.2283147}, pmid = {37990909}, issn = {1949-0984}, abstract = {Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.}, } @article {pmid37988085, year = {2023}, author = {Zhang, S and Huang, Y and Lu, G and Zhang, Z and Wang, Y and Liu, Y and Wang, W and Li, Q and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001025}, pmid = {37988085}, issn = {1728-7731}, abstract = {BACKGROUND: Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation, WMT) in the long-term management for IBD under the current health economic condition in China.

METHODS: Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security.

RESULTS: 60 eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine respectively (p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT respectively (p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1k CNY annually in the non-sustain phase but cut down the costs by 7.2k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment.

CONCLUSION: This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.}, } @article {pmid37986824, year = {2023}, author = {Berryhill, BA and Burke, KB and Fontaine, J and Brink, CE and Harvill, MG and Goldberg, DA and Konstantinidis, KT and Levin, BR and Woodworth, MH}, title = {Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Production.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.08.566299}, pmid = {37986824}, abstract = {UNLABELLED: Bioinformatic and experimental data show that bacteriophages are ubiquitous in human enteric microbiomes. However, there are gaps in understanding the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how these phages are maintained over time. To address these questions, we adapted and analyzed the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage and performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. However, phages can be maintained in these populations in high densities due to high rates of transition between resistant and sensitive states, which we call leaky resistance. Based on these models and observations, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in enteric microbiota is not yet clear, although O antigen production is broadly conserved across many taxa.

SIGNIFICANCE STATEMENT: Little is known about the role that bacteriophages play in shaping the bacterial species and strain composition in the human gut microbiome or how they are maintained over time in this dynamic environment. Here we show that Escherichia coli isolated from fecal samples are likely to be resistant to their co-existing phages due to production of the O antigen. However, phages can be maintained in populations of mostly resistant bacteria if there is a rapid transition between resistant and sensitive states, a state called leaky resistance. Based on these results, we postulate that bacteriophages are likely playing little role of shaping the abundance and diversity of bacteria in the human gut microbiome in healthy individuals.}, } @article {pmid37981872, year = {2023}, author = {Oliva-Hemker, M and Kahn, SA and Steinbach, WJ and , and , }, title = {Fecal Microbiota Transplantation: Information for the Pediatrician.}, journal = {Pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1542/peds.2023-062922}, pmid = {37981872}, issn = {1098-4275}, abstract = {Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.}, } @article {pmid37981746, year = {2023}, author = {Arora, U and Kedia, S and Ahuja, V}, title = {The practice of fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00085}, pmid = {37981746}, issn = {1598-9100}, abstract = {Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.}, } @article {pmid37981012, year = {2023}, author = {Zheng, M and Ye, H and Yang, X and Shen, L and Dang, X and Liu, X and Gong, Y and Wu, Q and Wang, L and Ge, X and Fang, X and Hou, B and Zhang, P and Tang, R and Zheng, K and Huang, XF and Yu, Y}, title = {Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {565-587}, doi = {10.1016/j.bbi.2023.11.016}, pmid = {37981012}, issn = {1090-2139}, abstract = {Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.}, } @article {pmid37979881, year = {2023}, author = {Liang, Y and Liu, D and Li, Y and Hou, H and Li, P and Ma, X and Li, P and Zhan, J and Wang, P}, title = {Maternal polysorbate 80 intake promotes offspring metabolic syndrome through vertical microbial transmission in mice.}, journal = {The Science of the total environment}, volume = {909}, number = {}, pages = {168624}, doi = {10.1016/j.scitotenv.2023.168624}, pmid = {37979881}, issn = {1879-1026}, abstract = {Polysorbate 80 (P80) is an emulsifier extensively produced, consumed and discharged into the environment, consequently making human exposure inevitable. Despite evidence suggesting that P80 intake causes metabolic syndrome (MS) in mammals via microbial perturbation, limited data exist on its transgenerational impacts on offspring. In this study, we found that maternal P80 treatment impaired intestinal barrier integrity, leading to metabolic endotoxemia, low-grade inflammation and MS-related symptoms in C57BL/6J female offspring. Further analysis of the gut microbiome revealed MS-related changes in the offspring of P80-treated dams. Fecal microbiota transplantation experiment confirmed the crucial role of the altered microbiome in offspring in the transgenerational impacts of P80. Furthermore, we found that the P80-induced microbial alterations were directly transmitted from P80-treated mothers to their offspring and that interrupting vertical microbial transmission through cesarean section and foster nursing blocked the transgenerational impacts of P80 on the offspring microbiome and metabolic health. Moreover, maternal pectin supplementation also effectively mitigated P80-induced microbial alterations and MS-associated phenotypes in offspring. Together, our results indicated that maternal P80 intake could impair offspring metabolic health through the mother-to-offspring transmission of the microbiome, and maternal pectin supplementation might be a promising strategy for reducing the adverse effects of P80.}, } @article {pmid37979452, year = {2023}, author = {Xi, D and Liu, P and Feng, Y and Teng, Y and Liang, Y and Zhou, J and Deng, H and Zeng, G and Zong, S}, title = {Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111212}, doi = {10.1016/j.intimp.2023.111212}, pmid = {37979452}, issn = {1878-1705}, abstract = {Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17[+] γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.}, } @article {pmid37979154, year = {2023}, author = {Kujawa, D and Laczmanski, L and Budrewicz, S and Pokryszko-Dragan, A and Podbielska, M}, title = {Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274126}, doi = {10.1080/19490976.2023.2274126}, pmid = {37979154}, issn = {1949-0984}, abstract = {Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.}, } @article {pmid37976078, year = {2023}, author = {Wang, Y and Wang, Z and Lu, Q}, title = {Microbiome dynamics in rheumatic diseases.}, journal = {Current opinion in rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/BOR.0000000000000993}, pmid = {37976078}, issn = {1531-6963}, abstract = {PURPOSE OF REVIEW: Rheumatic disease are characterized by their autoimmune nature, frequently affecting joints, bones, muscles, blood vessels, and connective tissues. The onset of these conditions typically unfolds gradually and subtly. It is noteworthy that individuals with rheumatic diseases often experience shifts in their microbiome, specifically on mucosal surfaces. The purpose of this review is to delve into the intricate interplay between the microbiome, encompassing bacteria, viruses and fungi, and its role in the development and aggravation of various rheumatic diseases. Additionally, it aims to offer insights into microbiome-centered therapeutic approaches for patients in the field of rheumatology.

RECENT FINDINGS: The advent of next-generation sequencing has significantly improved our understanding of microbiome changes. Numerous studies have consistently revealed a strong link between rheumatism and the microbiome, especially in the oral and gut microbiota.

SUMMARY: A deeper comprehension of the microbiome's connection to rheumatism holds potential for enhancing disease diagnosis and treatment. Targeted therapeutic approaches, including probiotics, fecal microbiota transplantation, and combination therapies with medications, offer promising avenues for disease management.}, } @article {pmid37975092, year = {2023}, author = {Guo, J and Zhou, B and Niu, Y and Liu, L and Yang, L}, title = {Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives.}, journal = {Journal of diabetes and metabolic disorders}, volume = {22}, number = {2}, pages = {1029-1038}, pmid = {37975092}, issn = {2251-6581}, abstract = {PURPOSE: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases.

METHODS: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023.

RESULTS: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease).

CONCLUSION: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.}, } @article {pmid37974103, year = {2023}, author = {Khan, FA and Pandupuspitasari, NS and Huang, C and Negara, W and Ahmed, B and Putri, EM and Lestari, P and Priyatno, TP and Prima, A and Restitrisnani, V and Surachman, M and Akhadiarto, S and Darmawan, IWA and Wahyuni, DS and Herdis, H}, title = {Unlocking gut microbiota potential of dairy cows in varied environmental conditions using shotgun metagenomic approach.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {344}, pmid = {37974103}, issn = {1471-2180}, mesh = {Female ; Cattle ; Animals ; *Lactation ; Diet/veterinary ; *Gastrointestinal Microbiome ; Milk Proteins ; Gases ; Methane/metabolism ; }, abstract = {Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.}, } @article {pmid37970585, year = {2022}, author = {Drefs, M and Schardey, J and von Ehrlich-Treuenstätt, V and Wirth, U and Burian, M and Zimmermann, P and Werner, J and Kühn, F}, title = {Endoscopic Treatment Options for Gastrointestinal Leaks.}, journal = {Visceral medicine}, volume = {38}, number = {5}, pages = {311-321}, pmid = {37970585}, issn = {2297-4725}, abstract = {BACKGROUND: Spontaneous or postoperative gastrointestinal defects are still life-threatening complications with elevated morbidity and mortality. Recently, endoscopic treatment options - up and foremost endoscopic vacuum therapy (EVT) - have become increasingly popular and have shown promising results in these patients.

METHODS: We performed an electronic systematic search of the MEDLINE databases (PubMed, EMBASE, and Cochrane) and searched for studies evaluating endoscopic options for the treatment of esophageal and colorectal leakages and/or perforations until March 2022.

RESULTS: The closure rate of both esophageal and colorectal defects by EVT is high and even exceeds the results of surgical revision in parts. Out of all endoscopic treatment options, EVT shows most evidence and appears to have the highest therapeutic success rates. Furthermore, EVT for both indications had a low rate of serious complications without relevant in-hospital mortality. In selected patients, EVT can be applied without fecal diversion and transferred to an outpatient setting.

CONCLUSION: Despite multiple endoscopic treatment options, EVT is increasingly becoming the new gold standard in endoscopic treatment of extraperitoneal defects of the upper and lower GI tract with localized peritonitis or mediastinitis and without close proximity to major blood vessels. However, further prospective, comparative studies are needed to strengthen the current evidence.}, } @article {pmid37969732, year = {2023}, author = {Zeng, X and Liao, Y and Qiao, X and Liang, K and Luo, Q and Deng, M and Liu, Y and Zhang, W and Hong, X and Xiao, Y}, title = {Novel NIR-II fluorescent probes for biliary atresia imaging.}, journal = {Acta pharmaceutica Sinica. B}, volume = {13}, number = {11}, pages = {4578-4590}, pmid = {37969732}, issn = {2211-3835}, abstract = {Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.}, } @article {pmid37967548, year = {2023}, author = {Naito, Y}, title = {Gut Frailty: Its Concept and Pathogenesis.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000534733}, pmid = {37967548}, issn = {1421-9867}, abstract = {BACKGROUND: There is still a considerable gap between average life expectancy and healthy life expectancy in Japan. Recent research has revealed that gut frailty may be a worsening factor for various diseases, a cause of chronic inflammation, and a precursor to frailty.

SUMMARY: Among self-reported symptoms, constipation is particularly significant as one of the key symptoms of gut frailty. Studies have demonstrated that individuals with constipation have significantly lower survival rates and are also at a higher risk of developing various diseases such as chronic kidney disease, cardiovascular diseases, and neurodegenerative disorders like Parkinson's disease. Various molecular mechanisms could contribute to gut frailty, and the decrease in mucus secretion is an extremely early-stage pathology. Dysbiosis of gut microbiota has a major impact on many conditions associated with gut frailty. Prebiotics, probiotics, post-biotics, and fecal microbiota transplantation are under investigation as a treatment option for gut frailty.

KEY MESSAGE: Although the concept of gut frailty has not yet gained widespread recognition, we hope to propose more practical screening methods, diagnostic approaches, and specific interventions in the future.}, } @article {pmid37966684, year = {2023}, author = {An, S and Zhen, Z and Wang, S and Sang, M and Zhang, S}, title = {Intestinal Microbiota Is a Key Target for Load Swimming to Improve Anxiety Behavior and Muscle Strength in Shank 3[-/-] Rats.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37966684}, issn = {1559-1182}, support = {7232239//Beijing Municipal Natural Science Foundation/ ; 21BTY023//National Social Science Fund of China/ ; 19YTA007//Key project of Beijing Social Science Foundation/ ; BNUXKJC2110//BNU Interdisciplinary Research Foundation for the First-Year Doctoral Candidates/ ; 20YJA890036//Research and planning fund for Humanities and social sciences of the Ministry of Education/ ; AEEA2020017//Priority topics of Beijing's 13th five year plan for Educational Science/ ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social disorder and stereotypical behavior, and its incidence rate is increasing yearly. It is considered that acritical period for the prognosis of young children with ASD exists, thus early treatment is crucial. Swimming, due to its comforting effect, is often used to induce enthusiasm in young children for completing activities and has a good effect in the treatment of ASD, but the effective path of swimming has yet to be reported. The intestinal microbiota of ASD patients and animal models has been reported to be different from that of healthy controls, and these changes may affect the brain environment. Therefore, whether the intestinal microbiota is involved in the treatment of ASD by early swimming is our concern. In this study, we used 8-day old Shank3 gene knockout rats with 8 weeks of early load swimming training and conducted behavioral, small intestine morphology, and intestinal content sequencing after training. The results showed that early load swimming significantly reduced the stereotyped and anxious behaviors of Shank3[-/-] rats, increased their muscle strength, increased the length of intestinal villi and the width of the muscular layer after Shank3 knockout, and affected the abundance of intestinal microorganisms. The abundances with statistical significance were Lactobacillus, Lachnospiraceae, and Alloprevotella. To further confirm the role of intestinal microorganisms in it, we designed a 14-day intestinal stool transplantation experiment. Fecal microbiota transplantation demonstrated that load swimming can significantly reduce the anxiety behavior of Shank3 rats, increase their muscle strength, change the structure of the small intestine, and affect the abundance of intestinal contents. The abundance of Epsilonbateraeota, Prevotella, and Bacteroides significantly changed after transplantation. Our findings confirm the possibility of early load swimming therapy for individuals with ASD and explain that the intestinal microbiota is a key pathway for early exercise therapy for patients with ASD.}, } @article {pmid37965266, year = {2023}, author = {Piazzesi, A and Pane, S and Russo, A and Del Chierico, F and Francalanci, P and Cotugno, N and Rossi, P and Locatelli, F and Palma, P and Putignani, L}, title = {Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1281440}, pmid = {37965266}, issn = {2235-2988}, abstract = {Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.}, } @article {pmid37962812, year = {2023}, author = {Lachmansingh, DA and Lavelle, A and Cryan, JF and Clarke, G}, title = {Microbiota-Gut-Brain Axis and Antidepressant Treatment.}, journal = {Current topics in behavioral neurosciences}, volume = {}, number = {}, pages = {}, pmid = {37962812}, issn = {1866-3370}, abstract = {In the treatment of depressive disorders, conventional antidepressant therapy has been the mainstay of clinical management, along with well-established nonpharmacological interventions such as various kinds of psychotherapy. Over the last 2 decades, there has been considerable interest in the role of the gastrointestinal system and its microbiota on brain function, behavior, and mental health. Components of what is referred to as the microbiota-gut-brain axis have been uncovered, and further research has elicited functional capabilities such as "gut-brain modules." Some studies have found associations with compositional alterations of gut microbiota in patients with depressive disorders and individuals experiencing symptoms of depression. Regarding the pathogenesis and neurobiology of depression itself, there appears to be a multifactorial contribution, in addition to the theories involving deficits in catecholaminergic and monoamine neurotransmission. Interestingly, there is evidence to suggest that antidepressants may play a role in modulating the gut microbiota, thereby possibly having an impact on the microbiota-gut-brain axis in this manner. The development of prebiotics, probiotics, and synbiotics has led to studies investigating not only their impact on the microbiota but also their therapeutic value in mental health. These psychobiotics have the potential to be used as therapeutic adjuncts in the treatment of depression. Regarding future directions, and in an attempt to further understand the role of the microbiota-gut-brain axis in depression, more studies such as those involving fecal microbiota transplantation will be required. In addition to recent findings, it is also suggested that more research will have to be undertaken to elicit whether specific strains of gut organisms are linked to depression. In terms of further investigation of the therapeutic potential of prebiotics, probiotics, and synbiotics as adjuncts to antidepressant treatment, we also expect there to be more research targeting specific microorganisms, as well as a strong focus on the effects of specific prebiotic fibers from an individualized (personalized) point of view.}, } @article {pmid37962207, year = {2023}, author = {Yang, T and Xie, S and Cao, L and Li, M and Ding, L and Wang, L and Pang, S and Wang, Z and Geng, L}, title = {Astragaloside IV modulates gut macrophages M1/M2 polarization by reshaping gut microbiota and SCFA in sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002262}, pmid = {37962207}, issn = {1540-0514}, abstract = {M1 macrophage-mediated inflammation is critical in sepsis. We previously found protective role of Astragaloside IV (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. Here, we aimed to investigate effects of AS-IV on gut macrophages polarization and potential roles of gut microbiota and short chain fatty acids (SCFA) in septic gut damage. Mice were pre-treated by AS-IV gavage for 7 days before cecal ligation and puncture (CLP). M1 polarization of gut lamina propria macrophages (LpMs) was promoted by CLP, accompanied by abnormal cytokines release and intestinal barrier dysfunction. NLRP3 inflammasome was activated in M1 LpMs. 16S rRNA sequencing demonstrated gut microbiota imbalance. The levels of acetate, propionate and butyrate in fecal samples decreased. Notably, AS-IV reversed LpMs M1/M2 polarization, lightened gut inflammation and barrier injury, reduced NLRP3 inflammasome expression in LpMs, restored the diversity of gut microbiome and increased butyrate levels. Similarly, these benefits were mimicked by fecal microbiota transplantation (FMT) or exogenous butyrate supplementation. In Caco-2 and THP-1 co-cultured model, lipopolysaccharide (LPS) and interferon-γ (IFN-γ) caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.}, } @article {pmid37961950, year = {2023}, author = {Guo, S and Shi, Y and Xu, A and Wang, Y and Xu, P}, title = {Liubao tea extract ameliorates ovalbumin-induced allergic asthma by regulating gut microbiota in mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo03470d}, pmid = {37961950}, issn = {2042-650X}, abstract = {Asthma, a chronic airway inflammatory disease, has a complicated pathogenesis and limited therapeutic treatment. Evidence shows that the intestinal microbiota exhibits crucial functional interaction with asthma syndrome. Liubao tea (LBT), a type of postfermented tea in China, positively modulates gut microbiota. However, the potential benefits of LBT extract (LBTE) for allergic asthma are still not understood. Herein, the anti-inflammatory effects of LBTE and its modulation of the gut microbiota of asthmatic mice induced by ovalbumin were explored. The results demonstrate that LBTE significantly inhibited airway hyper-responsiveness and restrained the proliferation of proinflammatory cytokines and inflammatory cells associated with allergic asthma. Additionally, LBTE suppressed inflammatory infiltration, mucus secretion, and excessive goblet cell production by downregulating the gene expression of inflammatory indicators. Interestingly, fecal microbiota transplantation results further implied that the modulation of LBTE on gut microbiota played an essential role in alleviating airway inflammatory symptoms of allergic asthma.}, } @article {pmid37961091, year = {2023}, author = {Dubey, H and Roychoudhury, R and Alex, A and Best, C and Liu, S and White, A and Carlson, A and Azcarate-Peril, MA and Mansfield, LS and Knickmeyer, R}, title = {Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.24.563309}, pmid = {37961091}, abstract = {UNLABELLED: The mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.

TEASER: Fecal transplants from human infants with highly abundant Bifidobacterium , an important inhabitant of the intestinal tract of breastfed newborns, may promote brain connectivity in mice.}, } @article {pmid37960284, year = {2023}, author = {Zheng, Y and Bonfili, L and Wei, T and Eleuteri, AM}, title = {Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, pmid = {37960284}, issn = {2072-6643}, support = {Fondi Studenti PhD//University of Camerino/ ; }, mesh = {Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy ; }, abstract = {The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.}, } @article {pmid37958637, year = {2023}, author = {Han, Z and Min, Y and Pang, K and Wu, D}, title = {Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, doi = {10.3390/ijms242115654}, pmid = {37958637}, issn = {1422-0067}, support = {2022-I2M-1-003//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Gastrointestinal Diseases/therapy ; Diarrhea ; Salmonella typhimurium ; }, abstract = {While emerging evidence highlights the significance of gut microbiome in gastrointestinal infectious diseases, treatments like Fecal Microbiota Transplantation (FMT) and probiotics are gaining popularity, especially for diarrhea patients. However, the specific role of the gut microbiome in different gastrointestinal infectious diseases remains uncertain. There is no consensus on whether gut modulation therapy is universally effective for all such infections. In this comprehensive review, we examine recent developments of the gut microbiome's involvement in several gastrointestinal infectious diseases, including infection of Helicobacter pylori, Clostridium difficile, Vibrio cholerae, enteric viruses, Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa Staphylococcus aureus, Candida albicans, and Giardia duodenalis. We have also incorporated information about fungi and engineered bacteria in gastrointestinal infectious diseases, aiming for a more comprehensive overview of the role of the gut microbiome. This review will provide insights into the pathogenic mechanisms of the gut microbiome while exploring the microbiome's potential in the prevention, diagnosis, prediction, and treatment of gastrointestinal infections.}, } @article {pmid37957893, year = {2023}, author = {Garner, W and Hamza, A and Haidar, G}, title = {Investigational non-antibiotic therapeutics for infections in hematopoietic cell transplant recipients and patients with hematologic malignancies receiving cellular therapies.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14193}, doi = {10.1111/tid.14193}, pmid = {37957893}, issn = {1399-3062}, abstract = {In the age of progressive antimicrobial resistance and increased difficulty combating infections in immunocompromised hosts, there has been renewed interest in the use of nontraditional therapeutics for infections. Herein, we review the use of investigational non-pharmaceutical anti-infective agents targeting fungal, bacterial, and viral infections in patients with hematologic malignancies, focusing on those receiving hematopoietic cell transplantation or cellular therapies. We discuss immune checkpoint inhibitors, granulocyte transfusions, bone marrow colony-stimulating factors, bacteriophages, fecal microbiota transplantation, and virus specific T-cell therapy. Although there is promising early experience with many of these treatments, further studies will be required to define their optimal role in the therapeutic armamentarium against infections in immunocompromised hosts.}, } @article {pmid37956701, year = {2023}, author = {Bornbusch, SL and Power, ML and Schulkin, J and Drea, CM and Maslanka, MT and Muletz-Wolz, CR}, title = {Integrating microbiome science and evolutionary medicine into animal health and conservation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.13030}, pmid = {37956701}, issn = {1469-185X}, support = {BCS 1749465//National Science Foundation/ ; IOS 2131060//National Science Foundation/ ; U4DMC39438//Pregnancy-Related Care Research Network (HRSA; HHS)/ ; //Smithsonian George E. Burch Fellowship in Theoretical Medicine and Affiliated Theoretical Science/ ; }, abstract = {Microbiome science has provided groundbreaking insights into human and animal health. Similarly, evolutionary medicine - the incorporation of eco-evolutionary concepts into primarily human medical theory and practice - is increasingly recognised for its novel perspectives on modern diseases. Studies of host-microbe relationships have been expanded beyond humans to include a wide range of animal taxa, adding new facets to our understanding of animal ecology, evolution, behaviour, and health. In this review, we propose that a broader application of evolutionary medicine, combined with microbiome science, can provide valuable and innovative perspectives on animal care and conservation. First, we draw on classic ecological principles, such as alternative stable states, to propose an eco-evolutionary framework for understanding variation in animal microbiomes and their role in animal health and wellbeing. With a focus on mammalian gut microbiomes, we apply this framework to populations of animals under human care, with particular relevance to the many animal species that suffer diseases linked to gut microbial dysfunction (e.g. gut distress and infection, autoimmune disorders, obesity). We discuss diet and microbial landscapes (i.e. the microbes in the animal's external environment), as two factors that are (i) proposed to represent evolutionary mismatches for captive animals, (ii) linked to gut microbiome structure and function, and (iii) potentially best understood from an evolutionary medicine perspective. Keeping within our evolutionary framework, we highlight the potential benefits - and pitfalls - of modern microbial therapies, such as pre- and probiotics, faecal microbiota transplants, and microbial rewilding. We discuss the limited, yet growing, empirical evidence for the use of microbial therapies to modulate animal gut microbiomes beneficially. Interspersed throughout, we propose 12 actionable steps, grounded in evolutionary medicine, that can be applied to practical animal care and management. We encourage that these actionable steps be paired with integration of eco-evolutionary perspectives into our definitions of appropriate animal care standards. The evolutionary perspectives proposed herein may be best appreciated when applied to the broad diversity of species under human care, rather than when solely focused on humans. We urge animal care professionals, veterinarians, nutritionists, scientists, and others to collaborate on these efforts, allowing for simultaneous care of animal patients and the generation of valuable empirical data.}, } @article {pmid37955340, year = {2023}, author = {Bibbò, S and Porcari, S and Del Vecchio, LE and Severino, A and Mullish, BH and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Gut microbiota and immunotherapy of renal cell carcinoma.}, journal = {Human vaccines & immunotherapeutics}, volume = {19}, number = {3}, pages = {2268982}, doi = {10.1080/21645515.2023.2268982}, pmid = {37955340}, issn = {2164-554X}, mesh = {Humans ; *Carcinoma, Renal Cell/therapy ; *Gastrointestinal Microbiome ; Immunotherapy ; *Kidney Neoplasms/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms ; }, abstract = {The gut microbiome has recently been proposed as a key player in cancer development and progression. Several studies have reported that the composition of the gut microbiome plays a role in the response to immune checkpoint inhibitors (ICIs). The gut microbiome modulation has been investigated as a potential therapeutic strategy for cancer, mainly in patients undergoing therapy with ICIs. In particular, modulation through probiotics, FMT or other microbiome-related approaches have proven effective to improve the response to ICIs. In this review, we examine the role of the gut microbiome in enhancing clinical responses to ICIs in the treatment of renal cancer.}, } @article {pmid37954280, year = {2023}, author = {Vasudevan, D and Ramakrishnan, A and Velmurugan, G}, title = {Exploring the diversity of blood microbiome during liver diseases: Unveiling Novel diagnostic and therapeutic Avenues.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21662}, pmid = {37954280}, issn = {2405-8440}, abstract = {Liver diseases are a group of major metabolic and immune or inflammation related diseases caused due to various reasons including infection, abnormalities in immune system, genetic defects, and lifestyle habits. However, the cause-effect relationship is not completely understood in liver disease. The role of microbiome, particularly, the role of gut and oral microbiome in liver diseases has been extensively studied in recent years. More interestingly, the presence of blood microbiome and tissue microbiome has been identified in many liver diseases. The translocation of microbes from the gut into the portal circulation has been attributed to be the major reason for the presence of blood microbial components and its clinical implications in liver disorders. Besides microbial translocation, Pathogen associated Molecular Patterns (PAMPs) derived from gut microbiota might also translocate. The presence of blood microbiome in liver disease has been reviewed earlier. However, the role of blood microbiome as a biomarker and therapeutic target in liver diseases has not been analysed earlier. In this review, we confabulate the origin and physiology of blood microbiome and blood microbial components in relation to the progression and pathogenesis of liver disease. In conclusion, we discuss the translational perspectives targeting the blood microbial components in the diagnosis and therapy of liver disease.}, } @article {pmid37953693, year = {2023}, author = {Lee, RB and Gasparetto, M}, title = {Novel pharmacological developments in the management of paediatric inflammatory bowel disease: Time for guideline update - A narrative review.}, journal = {Journal of paediatrics and child health}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpc.16519}, pmid = {37953693}, issn = {1440-1754}, abstract = {AIM: The incidence of paediatric inflammatory bowel disease (IBD) continues to increase in both adults and children across the globe, with more than one third of the patients not responding to anti-tumour necrosis factor biologics and immune modulators. This narrative review provides an overview of novel pharmacological developments in the management of paediatric IBD, including new biological therapies.

METHODS: A PubMed Medline search was performed to include randomised controlled trials, retrospective and prospective observational studies, and relevant case reports of children with IBD published between 2018 and January 2023. Guidelines and protocols from relevant paediatric and adult gastroenterology societies, such as the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation, were also included. Non-pharmacological treatments including therapeutic diets and faecal microbiota transplantation were outside the scope of this work.

RESULTS: Early real-world evidence suggests that newer biologics and small molecules, such as anti-integrins, interleukin-12 and/or interleukin-23 inhibitors, Janus kinase and signal transducer and activator of transcription proteins inhibitors, are safe and effective in adult patients with IBD, with promising growing evidence for paediatric IBD.

CONCLUSION: While many developments have been achieved with novel pharmacological treatments to manage IBD, ongoing research is required to confirm their effectiveness and safety in the paediatric age. Extending the licence of novel treatments to children will be crucial to tackle the increasing loss of response to conventional treatments. International guidelines will require timely updating to incorporate novel treatments within the existing protocols.}, } @article {pmid37951913, year = {2023}, author = {Mousavinasab, F and Karimi, R and Taheri, S and Ahmadvand, F and Sanaaee, S and Najafi, S and Halvaii, MS and Haghgoo, A and Zamany, M and Majidpoor, J and Khosravifar, M and Baniasadi, M and Talebi, M and Movafagh, A and Aghaei-Zarch, SM and Khorram, N and Farnia, P and Kalhor, K}, title = {Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.}, journal = {Cancer cell international}, volume = {23}, number = {1}, pages = {271}, pmid = {37951913}, issn = {1475-2867}, abstract = {Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.}, } @article {pmid37950332, year = {2023}, author = {Promsuwan, O and Malathum, K and Ingsathit, A}, title = {Epidemiology of extended-spectrum β-lactamase-producing Enterobacterales infection in kidney transplant recipients.}, journal = {Antimicrobial resistance and infection control}, volume = {12}, number = {1}, pages = {123}, pmid = {37950332}, issn = {2047-2994}, support = {ID 863//Faculty of Medicine Ramathibodi Hospital, Mahidol University/ ; }, mesh = {Humans ; Escherichia coli ; Prospective Studies ; *Kidney Transplantation/adverse effects ; beta-Lactamases ; *Bacteremia/epidemiology ; }, abstract = {BACKGROUND: Extended-spectrum b-lactamase (ESBL)-producing gram-negative bacilli (ESBL-GNB) are the most important pathogenic bacteria infecting kidney transplant patients. Kidney transplantation has been shown to be a risk factor for nosocomial ESBL-GNB bacteremia. The aims of this study were to describe the epidemiology of ESBL-GNB acquisition and to identify factors associated with ESBL-GNB infection in kidney transplant recipients, including pretransplant ESBL-GNB fecal carriage.

METHODS: A prospective study of patients undergoing kidney transplantation at Ramathibodi Hospital from March 1, 2019-November 30, 2020 was conducted. During this period, 66 patients who underwent kidney transplantation. Perianal swab cultures and urine cultures for ESBL-GNB were obtained from all subjects upon admission for transplantation and on Days 3, 7, 14 and 21 after surgery to determine the prevalence, incidence, and duration of admission before acquisition of the organisms.

RESULTS: Of the 66 patients undergoing kidney transplantation, 18 preoperative perianal swabs were detected to be positive for ESBL-GNB upon admission, representing 27.3% of the cases. The in-hospital perianal swab tests showed a significant increase to 96.8% positive ESBL-GNB cultures at the end of week 3. Approximately one-fourth (27.8%) of patients who acquired ESBL-GNB developed a postoperative symptomatic infection. The infection occurred in 13% of such patients who were not ESBL positive at first. These infections included urinary tract infections (20 cases, [30%], of which 55% were due to ESBL-GNB) and bloodstream infections (13 cases; of which 9 [69.2%] were due to ESBL-GNB). E. coli was the most common pathogen. Previous exposure to antibiotics, including surgical prophylaxis, underlying disease, duration of indwelling urinary catheters and ureteric stents, as well as other operative factors were not found to be significantly associated with the acquisition of ESBL-producing organisms in this dataset.

CONCLUSIONS: ESBL carriage may be a risk factor for the development of bacteremia and other serious infections among kidney transplant recipients, although a statistically significant difference could not be demonstrated owing to the small size of the sample. The high rate of ESBL acquisition suggests that more stringent infection prevention and control efforts are needed.}, } @article {pmid37948152, year = {2023}, author = {Song, W and Wang, Y and Li, G and Xue, S and Zhang, G and Dang, Y and Wang, H}, title = {Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276814}, doi = {10.1080/19490976.2023.2276814}, pmid = {37948152}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Molecular Weight ; Polysaccharides/pharmacology ; *Glycyrrhiza ; Immunity ; }, abstract = {Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4[+], CD8[+] T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.}, } @article {pmid37947218, year = {2023}, author = {Gudi, RR and Johnson, BM and Gaudreau, MC and Sun, W and Ball, L and Vasu, C}, title = {Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13713}, pmid = {37947218}, issn = {1365-2567}, support = {R21AI136339/NH/NIH HHS/United States ; R01AI138511/NH/NIH HHS/United States ; R01DK136094/NH/NIH HHS/United States ; }, abstract = {The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus-prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus-prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.}, } @article {pmid37944820, year = {2023}, author = {Zeng, K and Brewster, R and Kang, JB and Tkachenko, E and Brooks, E and Bhatt, AS and Fodor, AA and Andermann, TM}, title = {Acute steroid-refractory GI GVHD is not associated with significant differences in gut taxonomic composition compared to steroid-sensitive GI GVHD immediately prior to onset of disease: GI GVHD is not characterized by gut microbial differences preceding symptom onset.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2023.11.006}, pmid = {37944820}, issn = {2666-6367}, abstract = {BACKGROUND: Taxonomic composition of the gut microbiota at the time of neutrophil engraftment is associated with the development of acute gastrointestinal graft-versus-host disease (GI GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation. However, less is known about the relationship between the gut microbiota and development of steroid-refractory GI GVHD immediately prior to the onset of disease.

OBJECTIVES: Markers of steroid-refractory GI GVHD are needed in order to identify patients who may benefit from the early initiation of non-corticosteroid-based GVHD treatment. Our aim was to identify differences in taxonomic composition in stool samples from patients without GVHD, with steroid-responsive GVHD and with steroid-refractory GI GVHD in order to identify predictive microbiome biomarkers of steroid-refractory GI GVHD.

STUDY DESIGN: We conducted a retrospective case-control, single institution study, performing shotgun metagenomic sequencing on stool samples from patients with (n=36) and without GVHD (n=34) matched for time since transplant. We compared the taxonomic composition of the gut microbiome in those with steroid-sensitive GI GVHD (n=17) and steroid-refractory GI GVHD (n=19) to each other and to those without GVHD. We also performed associations between steroid-refractory GI GVHD, gut taxonomic composition, and fecal calprotectin, a marker of GI GVHD to develop composite fecal markers of steroid-refractory GVHD prior to the onset of GI disease.

RESULTS: We found that fecal samples within 30 days of GVHD onset from patients with and without GVHD or with and without steroid-refractory GI GVHD did not differ significantly in Shannon diversity (alpha-diversity) or in overall taxonomic composition (beta-diversity). While those patients without GVHD had higher relative abundance of Clostridium spp., those with and without steroid-refractory GI GVHD did not significantly differ in taxonomic composition between one another. In our study, fecal calprotectin prior to disease onset was significantly higher in patients with GVHD compared to those without GVHD and higher in patients with steroid-refractory GI GVHD compared to steroid-sensitive GI GVHD. No taxa were significantly associated with higher levels of calprotectin.}, } @article {pmid37944641, year = {2023}, author = {D, T and Venkatesh, MP}, title = {Fecal Microbiota Transplantation: History, Procedure and Regulatory Considerations.}, journal = {Presse medicale (Paris, France : 1983)}, volume = {}, number = {}, pages = {104204}, doi = {10.1016/j.lpm.2023.104204}, pmid = {37944641}, issn = {2213-0276}, abstract = {Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.}, } @article {pmid37942659, year = {2023}, author = {Normington, C and Chilton, CH and Buckley, AM}, title = {Clostridioides difficile infections; new treatments and future perspectives.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000000989}, pmid = {37942659}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.

RECENT FINDINGS: Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI.

SUMMARY: With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.}, } @article {pmid37942583, year = {2023}, author = {Wang, Q and Lin, H and Shen, C and Zhang, M and Wang, X and Yuan, M and Yuan, M and Jia, S and Cao, Z and Wu, C and Chen, B and Gao, A and Bi, Y and Ning, G and Wang, W and Wang, J and Liu, R}, title = {Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274124}, doi = {10.1080/19490976.2023.2274124}, pmid = {37942583}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Glucagon-Like Peptide 1/metabolism ; *Gastrointestinal Microbiome ; Signal Transduction ; Receptors, G-Protein-Coupled/genetics/metabolism ; Bile Acids and Salts ; Ileum ; }, abstract = {The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.}, } @article {pmid37939900, year = {2023}, author = {Bu, X and Pan, W and Liu, L and Wang, J and Yin, Z and Gao, Y and Ping, B}, title = {Human amniotic membrane-derived mesenchymal stem cells prevent acute graft-versus-host disease in an intestinal microbiome-dependent manner.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2023.11.005}, pmid = {37939900}, issn = {2666-6367}, abstract = {Acute graft-versus-host disease (aGVHD) represents a fatal severe complication following allogeneic hematopoietic stem cell transplantation. As a promising cell therapeutic strategy of aGVHD, the mechanism of mesenchymal stem cells (MSC) to ameliorate aGVHD has not been fully clarified, especially in the field of intestinal homeostasis including the intestinal microbiome involved in the pathogenesis of aGVHD. The present study aimed to explore the effect of MSC on intestinal homeostasis including the intestinal barrier and intestinal microbiome and its metabolites as well as the role of intestinal microbiome in the preventive process of hAMSCs ameliorating aGVHD. The preventive effects of human amniotic membrane-derived MSC (hAMSCs) was assessed in humanized aGVHD models. Immunohistochemistry and RT-qPCR were used to evaluate intestinal barrier function. 16S rRNA sequencing and targeted metabolomics assay were performed to observe the alternation of intestinal microbiome and the amounts of medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), respectively. Flow cytometer was performed to analyze the frequencies of T immune cells. Through animal experiments, we found that hAMSCs had the potential to prevent aGVHD. hAMSCs could repair the damage of intestinal barrier structure and function as well as improve the dysbiosis of intestinal microbiome induced by aGVHD, and meanwhile, upregulate the concentration of metabolites SCFAs, so as to reshape intestinal homeostasis. Gut microbiota depletion and fecal microbial transplantation confirmed the involvement of intestinal microbiome in the preventive process of hAMSCs on aGVHD. Our findings showed that hAMSCs prevented aGVHD in an intestinal microbiome-dependent manner, which might shed light on a new mechanism of hAMSCs inhibiting aGVHD and promote the development of new prophylaxis regimes for aGVHD prevention.}, } @article {pmid37938097, year = {2023}, author = {León-Janampa, N and Caballero-Posadas, I and Barc, C and Darrouzain, F and Moreau, A and Guinoiseau, T and Gatault, P and Fleurot, I and Riou, M and Pinard, A and Pezant, J and Rossignol, C and Gaudy-Graffin, C and Brand, D and Marlet, J}, title = {A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver.}, journal = {Hepatology communications}, volume = {7}, number = {11}, pages = {}, pmid = {37938097}, issn = {2471-254X}, mesh = {Humans ; Swine ; Animals ; *Hepatitis E ; Down-Regulation ; Viremia ; Tacrolimus ; Immunity, Innate/genetics ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is a zoonotic virus transmitted by pig meat and responsible for chronic hepatitis E in immunocompromised patients. It has proved challenging to reproduce this disease in its natural reservoir. We therefore aimed to develop a pig model of chronic hepatitis E to improve the characterization of this disease.

METHODS: Ten pigs were treated with a tacrolimus-based regimen and intravenously inoculated with HEV. Tacrolimus trough concentration, HEV viremia, viral diversity, innate immune responses, liver histology, clinical disease and biochemical markers were monitored for 11 weeks post-infection (p.i.).

RESULTS: HEV viremia persisted for 11 weeks p.i. HEV RNA was detected in the liver, small intestine, and colon at necropsy. Histological analysis revealed liver inflammation and fibrosis. Several mutations selected in the HEV genome were associated with compartmentalization in the feces and intestinal tissues, consistent with the hypothesis of extrahepatic replication in the digestive tract. Antiviral responses were characterized by a downregulation of IFN pathways in the liver, despite an upregulation of RIG-I and ISGs in the blood and liver.

CONCLUSIONS: We developed a pig model of chronic hepatitis E that reproduced the major hallmarks of this disease. This model revealed a compartmentalization of HEV genomes in the digestive tract and a downregulation of innate immune responses in the liver. These original features highlight the relevance of our model for studies of the pathogenesis of chronic hepatitis E and for validating future treatments.}, } @article {pmid37937304, year = {2023}, author = {Chen, Z and Guan, D and Wang, Z and Li, X and Dong, S and Huang, J and Zhou, W}, title = {Microbiota in cancer: molecular mechanisms and therapeutic interventions.}, journal = {MedComm}, volume = {4}, number = {6}, pages = {e417}, pmid = {37937304}, issn = {2688-2663}, abstract = {The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.}, } @article {pmid37937006, year = {2023}, author = {Secondo, D and Massaro, D and Verrienti, G and Perri, F and Biscaglia, G}, title = {Clostridioides difficile Infection in the Neurorehabilitation Setting: Importance of a Multidisciplinary Approach and Impact of the Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e46574}, pmid = {37937006}, issn = {2168-8184}, abstract = {Clostridioides difficile infection (CDI) is considered to be one of the most frequent causes of bacterial infectious diarrhea in nosocomial settings. The prolonged hospitalization in bed-ridden conditions and the frequent administration of antibiotic therapy are usually encountered among the risk factors for CDI. Therefore, it is not surprising that CDI rates among rehabilitation hospitals are higher in neurologic facilities. In the neurorehabilitation setting, CDIs, especially if they present with refractory or recurrent aspects, may interrupt the normal course of rehabilitation, influencing, subsequently, the neurological outcomes. CDI treatment depends on the severity of the disease and includes both conservative and surgical approaches, with the latter reserved for severe complicated CDI. Another emerging, highly effective therapeutic option is represented by fecal microbiota transplantation (FMT), which consists of the transfer of screened healthy donor stool to a recipient's gastrointestinal tract. In this paper, we report two cases of refractory CDI, affecting patients in the neurorehabilitation pathway; both cases were resolved through FMT. On the one hand, our cases provide more evidence of FMT efficacy in refractory CDIs; on the other hand, they emphasize the need for a multidisciplinary approach to grant the best care to CDI patients.}, } @article {pmid37936686, year = {2023}, author = {Reynolds, HM and Bettini, ML}, title = {Early-life microbiota-immune homeostasis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1266876}, pmid = {37936686}, issn = {1664-3224}, support = {T32 AI138945/AI/NIAID NIH HHS/United States ; R01 AI173406/AI/NIAID NIH HHS/United States ; R01 AI136963/AI/NIAID NIH HHS/United States ; }, mesh = {Infant, Newborn ; Humans ; *Probiotics/therapeutic use ; Dysbiosis ; *Microbiota ; *Gastrointestinal Microbiome ; Homeostasis ; }, abstract = {As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind microbiota-immune homeostasis has become critical for informing therapeutic interventions in cases of dysbiosis. Of particular importance, are alterations to intestinal microbiota occurring within the critical neonatal window, during which the immune system is highly vulnerable to environmental exposures. This review will highlight recent literature concerning mechanisms of early-life microbiota-immune homeostasis as well as discuss the potential for therapeutics in restoring dysbiosis in early life.}, } @article {pmid37936242, year = {2023}, author = {Pan, C and Zhang, H and Zhang, L and Chen, L and Xu, L and Xu, N and Liu, X and Meng, Q and Wang, X and Zhang, ZY}, title = {Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {248}, pmid = {37936242}, issn = {2049-2618}, support = {82201325//National Natural Science Foundation of China/ ; 82204382//National Natural Science Foundation of China/ ; 82071209//National Natural Science Foundation of China/ ; 21KJB310009//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; 22KJB310005//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, mesh = {Humans ; Aged ; Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/etiology ; RNA, Ribosomal, 16S ; *Cognitive Dysfunction ; Indoles/pharmacology ; Dexamethasone/pharmacology/therapeutic use ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.

METHODS: Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.

RESULTS: Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.

CONCLUSIONS: Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND. Video Abstract.}, } @article {pmid37935653, year = {2023}, author = {Pandey, H and Jain, D and Tang, DWT and Wong, SH and Lal, D}, title = {Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00080}, pmid = {37935653}, issn = {1598-9100}, abstract = {Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.}, } @article {pmid37935276, year = {2023}, author = {Ye, X and Sun, P and Lao, S and Wen, M and Zheng, R and Lin, Y and Gan, L and Fan, X and Wang, P and Li, Z and Yan, X and Zhao, L}, title = {Fgf21-Dubosiella axis mediates the protective effects of exercise against NAFLD development.}, journal = {Life sciences}, volume = {334}, number = {}, pages = {122231}, doi = {10.1016/j.lfs.2023.122231}, pmid = {37935276}, issn = {1879-0631}, abstract = {AIM: To explore the mechanism of gut microbiota mediates protective effects of exercise against non-alcoholic fatty liver disease (NAFLD) development.

MAIN METHODS: The male C57BL/6 mice were fed with high fat food (HFD) or normal diet (CON) respectively, and the obese mice were randomly divided into sedentariness (HFD) and exercise groups (HFD + Exe). The total intervention period was 18 weeks. Antibiotic treatment and fecal microbiota transplantation were applied to evaluate gut microbiota mediates the protective effects of exercise against NAFLD development. 16S rDNA profiling of gut microbiota and extracorporeal rehydration of Dubosiella newyorkensis were performed to identify the crucial role of Dubosiella in NAFLD improvement during exercise training. FGF21 knock-out mice were used to reveal the potential mechanism of exercise increased the abundance of Dubosiella. RT-PCR, Western blot, Histopathological examinations and Biochemical testing were performed to evaluate the lipid deposition and function in the liver.

KEY FINDINGS: Treadmill exercise significantly ameliorated hepatic function and mitigated lipid accumulation in NAFLD mice, and these hepatoprotective benefits were mostly mediated by the Dubosiella. In addition, the increased abundance of Dubosiella during exercise training was modulated by FGF21 specifically.

SIGNIFICANCE: In short, Dubosiella, chiefly regulated by FGF21 signaling during exercise training, has been discovered to govern the protective impacts of exercising counter to the development of NAFLD and exhibits a promising treatment target for NAFLD.}, } @article {pmid37934614, year = {2023}, author = {Zhang, T and Gao, G and Kwok, LY and Sun, Z}, title = {Gut microbiome-targeted therapies for Alzheimer's disease.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2271613}, pmid = {37934614}, issn = {1949-0984}, abstract = {The advent of high-throughput 'omics' technologies has improved our knowledge of gut microbiome in human health and disease, including Alzheimer's disease (AD), a neurodegenerative disorder. Frequent bidirectional communications and mutual regulation exist between the gastrointestinal tract and the central nervous system through the gut-brain axis. A large body of research has reported a close association between the gut microbiota and AD development, and restoring a healthy gut microbiota may curb or even improve AD symptoms and progression. Thus, modulation of the gut microbiota has become a novel paradigm for clinical management of AD, and emerging effort has focused on developing potential novel strategies for preventing and/or treating the disease. In this review, we provide an overview of the connection and causal relationship between gut dysbiosis and AD, the mechanisms of gut microbiota in driving AD progression, and the successes and challenges of implementing available gut microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) in preventive and/or therapeutic preclinical and clinical intervention studies of AD. Finally, we discuss the future directions in this field.}, } @article {pmid37934064, year = {2023}, author = {Cao, Y and Zhang, L and Xiong, F and Guo, X and Kan, X and Song, S and Liang, B and Liang, B and Yu, L and Zheng, C}, title = {Effect of probiotics and fecal microbiota transplantation in dirty rats with established primary liver cancer.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {}, doi = {10.2217/fmb-2022-0234}, pmid = {37934064}, issn = {1746-0921}, abstract = {Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials & methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of β-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.}, } @article {pmid37933950, year = {2023}, author = {Zhang, M and Mo, R and Wang, H and Liu, T and Zhang, G and Wu, Y}, title = {Grape seed proanthocyanidin improves intestinal inflammation in canine through regulating gut microbiota and bile acid compositions.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {12}, pages = {e23285}, doi = {10.1096/fj.202300819RR}, pmid = {37933950}, issn = {1530-6860}, mesh = {Dogs ; Animals ; *Gastrointestinal Microbiome ; Bile Acids and Salts ; *Inflammatory Bowel Diseases/microbiology ; Inflammation ; Polyphenols/pharmacology ; }, abstract = {Although certain progress has been made in treating canine inflammatory bowel disease (IBD), a large proportion of dogs have a poor prognosis and may develop resistance and side effects. Therefore, it is of great significance to prevent or alleviate canine IBD through nutritional intervention. Plant polyphenol can interact with intestinal bacteria and has important prospects in the intestinal health improvement. This study evaluated the effect of grape seed proanthocyanidin (GSP), a plant-derived natural polyphenol, on Labrador Retrievers with mild IBD. In Experiment 1 of this study, GSP alleviated persistent intestinal inflammation in canines by improving inflammatory indexes and reducing intestinal permeability. Moreover, GSP treatment increased the abundance of bacteria with potential anti-inflammatory properties and engaging bile acid metabolism, including Ruminococcaceae, Faecalibacterium, Ruminococcus_torques_group, and Lachnospiraceae_NK4A136_group. Notably, targeted metabolomic analysis identified elevated productions of fecal chenodeoxycholic acid and its microbial transformation product lithocholic acid, which might contribute to relieving canine intestinal inflammation. Further, in Experiment 2, fecal microbiota transplantation was used to determine whether gut microbiota is a potential mechanism for GSP efficacy. Dogs with mild IBD received the fecal microbiota from the group administered GSP and mirrored the improvement effects of GSP, which results verified that gut microbial alteration could be an underlying mechanism for GSP efficiency on canine IBD. Our findings highlight that the mechanism of the GSP function on canine IBD is mediated by altering gut microbial composition and improving bile acid metabolism. This study proposes a natural polyphenol-based dietary strategy for improving canine intestinal health.}, } @article {pmid37932511, year = {2023}, author = {Blake, SJ and Wolf, Y and Boursi, B and Lynn, DJ}, title = {Role of the microbiota in response to and recovery from cancer therapy.}, journal = {Nature reviews. Immunology}, volume = {}, number = {}, pages = {}, pmid = {37932511}, issn = {1474-1741}, abstract = {Our understanding of how the microbiota affects the balance between response to and failure of cancer treatment by modulating the tumour microenvironment and systemic immune system has advanced rapidly in recent years. Microbiota-targeting interventions in patients with cancer are an area of intensive investigation. Promisingly, phase I-II clinical trials have shown that interventions such as faecal microbiota transplantation can overcome resistance to immune checkpoint blockade in patients with melanoma, improve therapeutic outcomes in treatment-naive patients and reduce therapy-induced immunotoxicities. Here, we synthesize the evidence showing that the microbiota is an important determinant of both cancer treatment efficacy and treatment-induced acute and long-term toxicity, and we discuss the complex and inter-related mechanisms involved. We also assess the potential of microbiota-targeting interventions, including bacterial engineering and phage therapy, to optimize the response to and recovery from cancer therapy.}, } @article {pmid37928687, year = {2023}, author = {Okamura, T and Hasegawa, Y and Hamaguchi, M and Sasano, R and Fukui, M}, title = {The role of chicken eggs in modulating sarcopenic obesity and gut microbiota in db/db mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281217}, pmid = {37928687}, issn = {1664-302X}, abstract = {BACKGROUND: Sarcopenia obesity, in which loss of muscle mass and fat accumulation occur simultaneously, is the pathological basis of type 2 diabetes mellitus. The usefulness of chicken eggs in sarcopenia prevention has been reported in several previous studies. The purpose of this study was to determine the beneficial effects of chicken eggs in the prevention of sarcopenic obesity in db/db mice.

METHODS: We raised 8-week-old db/db male mice, a model of sarcopenia obesity, for 8 weeks and fed them a diet mixed with dried whole eggs. The fecal microbiota transplant (FMT) group was treated with antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age.

RESULTS: Eggs administered to db/db mice showed increased grip strength (p = 0.022) and muscle mass (p = 0.013), decreased visceral fat mass (p = 0.005), and significantly increased physical activity (p < 0.001). The FMT group of egg-fed mice showed a significant improvement in glucose intolerance and sarcopenic obesity. Sequencing of gene expression in the small intestine showed that the gene expression of amino acid transporters such as Slc6a18, Slc6a19, and Slc38a6 was increased in egg-fed mice. 16S rRNA sequencing of the gut microbiota showed an increase in the genus Vampirovibrio in both the egg-fed and FMT groups compared to that in egg-fed mice.

CONCLUSION: The results of this study indicate that egg consumption not only increases the intake of amino acids and other nutrients but also alters the intestinal microbiota and increases amino acid absorption from the intestinal tract, suggesting that eggs might contribute to the ameliorative mechanism of sarcopenic obesity.}, } @article {pmid37927130, year = {2023}, author = {Lee, J and Kim, EJ and Park, GS and Kim, J and Kim, TE and Lee, YJ and Park, J and Kang, J and Koo, JW and Choi, TY}, title = {Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.}, journal = {Experimental neurobiology}, volume = {32}, number = {5}, pages = {313-327}, pmid = {37927130}, issn = {1226-2560}, abstract = {Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.}, } @article {pmid37922956, year = {2023}, author = {Pilonis, N}, title = {Positive fecal immunochemical test but negative colonoscopy: what's next?.}, journal = {Endoscopy}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2182-6316}, pmid = {37922956}, issn = {1438-8812}, } @article {pmid37923839, year = {2023}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-023-02650-8}, pmid = {37923839}, issn = {1546-170X}, } @article {pmid37921501, year = {2023}, author = {Wang, H and Bi, H and Yang, M and Wang, X and Song, C and Yang, W and Wang, Y and Xie, D and Li, H and Zhou, Z}, title = {Intestinal flora altered and correlated with interleukin-2/4 in patients with primary immune thrombocytopenia.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {28}, number = {1}, pages = {2277501}, doi = {10.1080/16078454.2023.2277501}, pmid = {37921501}, issn = {1607-8454}, mesh = {Humans ; *Purpura, Thrombocytopenic, Idiopathic ; Interleukin-2 ; *Gastrointestinal Microbiome ; Interleukin-4 ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Little is known about the changes and mechanisms of intestinal flora in primary immune thrombocytopenia (ITP) patients.

AIM: To explore the structural and functional differences of intestinal flora between ITP patients and healthy controls, and clarify the correlation between intestinal flora and Th1/Th2 imbalance.

METHODS: Feces from ITP patients and healthy controls were studied by 16S rRNA and metagenomic techniques at phylum, genus, species or functional levels. Blood samples were collected for the detection of interleukin -2 (IL-2) and IL-4 concentrations.

RESULTS: The following changes in ITP patients were found: a decrease of Bacteroidetes phylum, an increase of Proteobacteria phylum and alterations of ten genera and 1045 species. IL-2 and IL-4 were significantly correlated with six and five genera, respectively. Species of C. freundii, C. rodentium, and C. youngae were negatively correlated with bleeding scores, and S. infantis was positively related to platelet counts. Functionally, the intestinal flora of ITP patients changed mainly in terms of motility, chemotaxis, membrane transport, and metabolism.

CONCLUSION: The mechanism underlying functional and structural changes of intestinal flora in ITP patients may be related to inflammation and immunity, providing possibilities of probiotics or fecal transplants for ITP.}, } @article {pmid37918500, year = {2023}, author = {Feng, W and Zhang, Y and Zhang, Y and Dong, Y and Wu, J and Chen, Q and Liu, M and Wang, D and Wu, Y and Wang, T}, title = {Anemoside B4 ameliorates dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome and modulating gut microbiota.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {176164}, doi = {10.1016/j.ejphar.2023.176164}, pmid = {37918500}, issn = {1879-0712}, abstract = {Ulcerative colitis (UC) has been recognized as a chronic and relapsing inflammatory disease of the gastrointestinal tract. Clinically, aminosalicylates, immunosuppressants and biological agents are commonly used to treat UC at different stages of the disease. However, these drugs often have side effects. Here, we investigated the anti-UC activity of Anemoside B4 (AB4) in mice with dextran sulfate sodium (DSS) induced colitis. Colon tissues, serum, and colonic contents were collected for assessment of intestinal barrier function, inflammatory cytokines production and microenvironment of intestinal microbiota. Results showed that AB4 alleviated colon shortening, weight lossing and histopathological damage in DSS-induced mice. In addition, we demonstrated both in vivo and in vitro that AB4 remarkably ameliorated colonic inflammation through suppressing NLRP3 pathway. Moreover, AB4 strengthened the intestinal epithelial barrier by regulating myosin light chain kinase (MLCK)-phosphorylated myosin light chain 2 (pMLC2) signaling pathway. Furthermore, we performed 16 S rRNA gene sequencing and fecal microbiome transplantation (FMT) experiments to demonstrate that AB4 alleviated colitis through regulating dysbiosis of intestinal microbiota. These results revealed that AB4 effectively ameliorate experimental UC mainly through regulating MLCK/pMLC2 pathway, NLRP3 pathway and dysbiosis of microbiota, provided new insights into the development of novel anti-UC drugs.}, } @article {pmid37918459, year = {2023}, author = {Ross, FC and Mayer, DE and Gupta, A and Richard Gill, CI and Del Rio, D and Cryan, JF and Lavelle, A and Ross, RP and Stanton, C and Mayer, EA}, title = {Existing and future strategies to manipulate the gut microbiota with diet as a potential adjuvant treatment for psychiatric disorders.}, journal = {Biological psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biopsych.2023.10.018}, pmid = {37918459}, issn = {1873-2402}, abstract = {Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and non-dietary interventions, particularly fecal microbial transplants. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.}, } @article {pmid37918425, year = {2023}, author = {Scharl, M and Rogler, G}, title = {[Microbiome: from pathophysiology to clinical application?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {148}, number = {22}, pages = {1419-1424}, doi = {10.1055/a-1951-0063}, pmid = {37918425}, issn = {1439-4413}, mesh = {Humans ; *Clostridium Infections/therapy ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Microbiota ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {The "microbiome" or the intestinal microbiota is currently in the focus of scientific interest. The number of publications on the topic of the microbiome is increasing every year. In particular, the role of the microbiome in the pathophysiology of various diseases has been studied. Currently it is impossible to have an overview on all new developments with over 25.000 publication in the field per year. However, some key news stand out from this large number of publications. The first microbiota compounds for the therapy of Clostridioides difficile colitis were approved by the FDA last year or are about to be approved. This means that, for the first time, standardized microbiome products are available in addition to fecal microbiota transplantation (FMT) and are finding their way into everyday clinical practice.}, } @article {pmid37916626, year = {2023}, author = {Zhang, L and Ma, XG}, title = {A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components.}, journal = {Combinatorial chemistry & high throughput screening}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113862073257733231011072004}, pmid = {37916626}, issn = {1875-5402}, abstract = {BACKGROUND: The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability.

METHODS: The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI.

RESULTS: This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people.

CONCLUSION: To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.}, } @article {pmid37915416, year = {2023}, author = {Zhang, D and Tang, Y and Bai, X and Li, D and Zhou, M and Yu, C and Wu, H}, title = {Efficacy and safety of fecal microbiota transplantation for the treatment of irritable bowel syndrome: an overview of overlapping systematic reviews.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1264779}, pmid = {37915416}, issn = {1663-9812}, abstract = {Aim: Evidence from overlapping systematic reviews (SRs) and meta-analyses (MAs) has yielded conflicting results on the treatment of irritable bowel syndrome (IBS) with fecal microbiota transplantation (FMT). To thoroughly gather, assess, and synthesize evidence on FMT for IBS, we carried out the present study. Methods: A comprehensive search was conducted in Cochrane Library, Web of Science, PubMed, and Embase from inception to May 2023. Tools for assessing the methodological quality, reporting quality, and confidence in outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Seven eligible SRs/MAs were finally included in this overview. By AMSTAR-2, the methodological quality of SRs/MAs included five that were very low quality, one that was low quality, and one that was high quality. According to PRISMA, limitations were associated with items 5 (Method: Protocol and Registration), 8 (Method: Search), and 27 (Funding). In GRADE, a total of 19 outcomes were included in the seven reviews, of which 12 outcomes were low quality and seven outcomes were moderate quality. Imprecision due to small sample size was the primary factor leading to evidence downgrading. Conclusion: We conclude that there is insufficient evidence to determine whether FMT has a more beneficial effect on patient with IBS than placebo treatment. Well-designed, larger trails are needed to provide evidence in this field. In addition, selection of donor, route of administration, dosage, and frequency still need to be determined.}, } @article {pmid37915336, year = {2023}, author = {Carrington, AE and Maloh, J and Nong, Y and Agbai, ON and Bodemer, AA and Sivamani, RK}, title = {The Gut and Skin Microbiome in Alopecia: Associations and Interventions.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {16}, number = {10}, pages = {59-64}, pmid = {37915336}, issn = {1941-2789}, abstract = {OBJECTIVE: This review examines the current literature on the gut-skin connection in alopecia and summarizes interventions that impact hair growth by modulation of the gut or skin microbiome.

METHODS: PubMed searches were done to assess studies of the gut and skin microbiome and forms of alopecia including, alopecia areata (AA), androgenic alopecia (AGA), alopecia universalis (AU), central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP). Filters were applied for human and animal studies. Articles not translated to English and studies assessing supplemental therapies on alopecia were excluded.

RESULTS: There is evidence that scalp, hair follicle, and gut microbiome alterations are associated with various types of alopecia. There is potential in the use of interventions targeting microbiome dysbiosis, including fecal transplants and probiotics.

LIMITATIONS: This field of study still requires more high-quality research and studies with larger participant populations.

CONCLUSION: Dysbiosis on the scalp, within the hair follicle and the gut seem to have a role in the pathophysiology of various forms of alopecia. There is evidence that interventions targeting dysbiosis may have potential in the treatment and management of hair loss. Further studies are needed to establish a direct connection and to clarify specific effects of these interventions.}, } @article {pmid37914662, year = {2023}, author = {Yu, Y and Wang, W and Zhang, F}, title = {The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2301097}, doi = {10.1002/advs.202301097}, pmid = {37914662}, issn = {2198-3844}, support = {2021YFA0717004//National Key Research and Development Program of China/ ; //Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for dysbiosis-related diseases. However, the clinical practice of crude fecal transplants presents limitations in terms of acceptability and reproductivity. Consequently, two alternative solutions to FMT are developed: transplanting bacteria communities or virome. Advanced methods for transplanting bacteria mainly include washed microbiota transplantation and bacteria spores treatment. Transplanting the virome is also explored, with the development of fecal virome transplantation, which involves filtering the virome from feces. These approaches provide more palatable options for patients and healthcare providers while minimizing research heterogeneity. In general, the evolution of the next generation of FMT in global trends is fecal microbiota components transplantation which mainly focuses on transplanting bacteria or virome.}, } @article {pmid37914097, year = {2023}, author = {He, H and He, H and Mo, L and You, Z and Zhang, J}, title = {Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {280-294}, doi = {10.1016/j.bbi.2023.10.031}, pmid = {37914097}, issn = {1090-2139}, abstract = {BACKGROUND: Mental disorders may be involved in neuroinflammatory processes that are triggered by gut microbiota. How gut microbiota influence microglia-mediated sensitivity to stress remains unclear. Here we explored in an animal model of depression whether disruption of the gut microbiome primes hippocampal microglia, thereby impairing neurogenesis and sensitizing to stress.

METHODS: Male C57BL/6J mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, and effects on gut microbiota were assessed using 16S rRNA sequencing. Fecal microbiota was transplanted from control or CUMS mice into naïve animals. The depression-like behaviors of recipients were evaluated in a forced swimming test and sucrose preference test. The morphology and phenotype of microglia in the hippocampus of recipients were examined using immunohistochemistry, quantitative PCR, and enzyme-linked immunosorbent assays. The recipients were treated with lipopolysaccharide or chronic stress exposure, and effects were evaluated on behavior, microglial responses and hippocampal neurogenesis. Finally, we explored the ability of minocycline to reverse the effects of CUMS on hippocampal neurogenesis and stress sensitivity in recipients.

RESULTS: CUMS altered the gut microbiome, leading to higher relative abundance of some bacteria (Helicobacter, Bacteroides, and Desulfovibrio) and lower relative abundance of some bacteria (Lactobacillus, Bifidobacterium, and Akkermansia). Fecal microbiota transplantation from CUMS mice to naïve animals induced microglial priming in the dentate gyrus of recipients. This microglia showed hyper-ramified morphology, and became more sensitive to LPS challenge or chronic stress, which characterized by more significant morphological changes and inflammatory responses, as well as impaired hippocampal neurogenesis and increased depressive-like behaviors. Giving minocycline to recipients reversed these effects of fecal transplantation.

CONCLUSIONS: These findings suggest that gut microbiota from stressed animals can induce microglial priming in the dentate gyrus, which is associated with a hyper-immune response to stress and impaired hippocampal neurogenesis. Remodeling the gut microbiome or inhibiting microglial priming may be strategies to reduce sensitivity to stress.}, } @article {pmid37910603, year = {2023}, author = {Woodworth, MH and Conrad, RE and Haldopoulos, M and Pouch, SM and Babiker, A and Mehta, AK and Sitchenko, KL and Wang, CH and Strudwick, A and Ingersoll, JM and Philippe, C and Lohsen, S and Kocaman, K and Lindner, BG and Hatt, JK and Jones, RM and Miller, C and Neish, AS and Friedman-Moraco, R and Karadkhele, G and Liu, KH and Jones, DP and Mehta, CC and Ziegler, TR and Weiss, DS and Larsen, CP and Konstantinidis, KT and Kraft, CS}, title = {Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.}, journal = {Science translational medicine}, volume = {15}, number = {720}, pages = {eabo2750}, doi = {10.1126/scitranslmed.abo2750}, pmid = {37910603}, issn = {1946-6242}, abstract = {Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.}, } @article {pmid37909786, year = {2023}, author = {Richie, TG and Heeren, L and Kamke, A and Monk, K and Pogranichniy, S and Summers, T and Wiechman, H and Ran, Q and Sarkar, S and Plattner, BL and Lee, STM}, title = {Limitation of amino acid availability by bacterial populations during enhanced colitis in IBD mouse model.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0070323}, doi = {10.1128/msystems.00703-23}, pmid = {37909786}, issn = {2379-5077}, abstract = {Members of the Enterobacteriaceae and Enterococcus are associated with persistent gut inflammation due to rapid colonization combined with pathogenic tendencies. Here, we investigated the functions of gut microbial populations resulting in persistent gut inflammation. In this study, we utilized the IL-10 knockout mouse model and induced colitis using dextran sulfate sodium (2%) after development. Dams during gestation were provided cefoperazone to induce vertically transmitted dysbiosis in the pups that were monitored in this study. We characterized the dysbiotic gut microbial community and potential crosstalk of these microbes, and host gene expression changes to identify bacterial populations and potential functions that were involved in gut inflammation. We isolated Enterobacteriaceae populations from mice to validate the utilization of sulfur-containing amino acids. Members of Enterobacteriaceae and Enterococcus were highly detected in inflamed mice. Enterobacteriaceae populations containing L-cysteine dioxygenase were strongly correlated with the upregulation of host gene CSAD, responsible for cysteine breakdown. We observed that bacterial isolates from dysbiotic mice displayed increased growth rates when supplemented with L-cysteine, highlighting the use of sulfur metabolism. Our results show that microbial populations use alternate metabolisms and sequester host nutrients for growth, associated with inflammation in the gut.IMPORTANCEInflammatory bowel disease is associated with an increase in Enterobacteriaceae and Enterococcus species; however, the specific mechanisms are unclear. Previous research has reported the associations between microbiota and inflammation, here we investigate potential pathways that specific bacteria populations use to drive gut inflammation. Richie et al. show that these bacterial populations utilize an alternate sulfur metabolism and are tolerant of host-derived immune-response products. These metabolic pathways drive host gut inflammation and fuel over colonization of these pathobionts in the dysbiotic colon. Cultured isolates from dysbiotic mice indicated faster growth supplemented with L-cysteine, showing these microbes can utilize essential host nutrients.}, } @article {pmid37906091, year = {2023}, author = {Zhou, H and Yu, B and Sun, J and Chen, H and Liu, Z and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect diarrhea: an investigation in the germ-free piglet model.}, journal = {Animal biotechnology}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/10495398.2023.2248200}, pmid = {37906091}, issn = {1532-2378}, abstract = {This experiment was conducted to explore the effects of gut microbiota on neonatal diarrhea in a germ-free (GF) pig model. Twelve hysterectomy-derived GF piglets were housed in six sterile isolators. Among them, six piglets were treated as the GF group, and the other six piglets were orally introduced with healthy sow fecal suspension and regarded as the fecal microbiota transplantation (FMT) group. Another six piglets from natural birth were considered as the conventional (CV) group. The GF and FMT piglets were hand-fed with sterile milk powder for 21 days, and the CV piglets were suckled for the same days. Then, all piglets were fed with sterile feed for another 21 days. Results exhibited that the GF group's fecal score and moisture level were higher than those in the CV and FMT groups (p < 0.05). Meanwhile, the abundances of colonic AQP1 and AQP8 in the GF group were the greatest among these treatments (p < 0.05). However, FMT piglets had a lower fecal score in d 22-28 and d 29-35 than that in the CV piglets (p < 0.05). Collectively, the absence of gut microbiota may cause diarrhea in the piglet model, and transplantation of maternal fecal microbiota may reverse it.}, } @article {pmid37905694, year = {2023}, author = {Tian, X and Wang, G and Teng, F and Xue, X and Pan, J and Mao, Q and Guo, D and Song, X and Ma, K}, title = {Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota-gut-brain axis in corticosterone combined with chronic restraint stress-induced mice.}, journal = {CNS neuroscience & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14519}, pmid = {37905694}, issn = {1755-5949}, support = {//National Natural Science Foundation of China/ ; //Natural Science Foundation of Shandong Province/ ; //Shandong Province Universities' Development Plan for Youth Innovation Teams/ ; }, abstract = {BACKGROUND: The microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.

MATERIALS AND METHODS: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.

RESULTS: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression.

CONCLUSIONS: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.}, } @article {pmid37902074, year = {2023}, author = {Balzano, T and Llansola, M and Arenas, YM and Izquierdo-Altarejos, P and Felipo, V}, title = {Hepatic encephalopathy: investigational drugs in preclinical and early phase development.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {}, doi = {10.1080/13543784.2023.2277386}, pmid = {37902074}, issn = {1744-7658}, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, in patients with liver disease, which affects life quality and span. Current treatments are lactulose or rifaximin, acting on gut microbiota. Treatments aiming ammonia levels reduction have been tested with little success.

AREAS COVERED: Pre-clinical research shows that the process inducing HE involves sequentially: liver failure, altered microbiome, hyperammonemia, peripheral inflammation, changes in immunophenotype and extracellular vesicles and neuroinflammation which alters neurotransmission impairing cognitive and motor function. HE may be reversed using drugs acting at any step: modulating microbiota with probiotics or fecal transplantation; reducing peripheral inflammation with anti-TNFα, autotaxin inhibitors or silymarin; reducing neuroinflammation with sulforaphane, p38 MAP kinase or phosphodiesteras 5, antagonists of sphingosine-1-phosphate receptor2, enhancing meningeal lymphatic drainage or with extracellular vesicles from mesenchymal stem cells; reducing GABAergic neurotransmission with indomethacin or golexanolone.

EXPERT OPINION: A factor limiting the progress of HE treatment is the lack of translation of research advances into clinical trials. Only drugs acting on microbiota or ammonia reduction have been tested in patients. t is urgent to change the mentality on how to approach HE treatment to develop clinical trials to assess drugs acting on the immune system/peripheral inflammation, neuroinflammation or neurotransmission to improve HE.}, } @article {pmid37896894, year = {2023}, author = {Louge Uriarte, EL and Badaracco, A and Spetter, MJ and Miño, S and Armendano, JI and Zeller, M and Heylen, E and Späth, E and Leunda, MR and Moreira, AR and Matthijnssens, J and Parreño, V and Odeón, AC}, title = {Molecular Epidemiology of Rotavirus A in Calves: Evolutionary Analysis of a Bovine G8P[11] Strain and Spatio-Temporal Dynamics of G6 Lineages in the Americas.}, journal = {Viruses}, volume = {15}, number = {10}, pages = {}, pmid = {37896894}, issn = {1999-4915}, support = {AESA 203971 and PNSA 1115053//Instituto Nacional de Tecnología Agropecuaria (INTA)/ ; PICT N 38308//Ministerio de Ciencia, Tecnología e Innovación (MINCyT)/ ; }, mesh = {Animals ; Cattle ; *Rotavirus/genetics ; Molecular Epidemiology ; Phylogeny ; *Rotavirus Infections/epidemiology/veterinary ; Diarrhea/epidemiology/veterinary ; Genotype ; Feces ; *Cattle Diseases/epidemiology ; }, abstract = {Rotavirus A (RVA) causes diarrhea in calves and frequently possesses the G6 and P[5]/P[11] genotypes, whereas G8 is less common. We aimed to compare RVA infections and G/P genotypes in beef and dairy calves from major livestock regions of Argentina, elucidate the evolutionary origin of a G8 strain and analyze the G8 lineages, infer the phylogenetic relationship of RVA field strains, and investigate the evolution and spatio-temporal dynamics of the main G6 lineages in American countries. Fecal samples (n = 422) from diarrheic (beef, 104; dairy, 137) and non-diarrheic (beef, 78; dairy, 103) calves were analyzed by ELISA and semi-nested multiplex RT-PCR. Sequencing, phylogenetic, phylodynamic, and phylogeographic analyses were performed. RVA infections were more frequent in beef (22.0%) than in dairy (14.2%) calves. Prevalent genotypes and G6 lineages were G6(IV)P[5] in beef (90.9%) and G6(III)P[11] (41.2%) or mixed genotypes (23.5%) in dairy calves. The only G8 strain was phylogenetically related to bovine and artiodactyl bovine-like strains. Re-analyses inside the G8 genotype identified G8(I) to G8(VIII) lineages. Of all G6 strains characterized, the G6(IV)P[5](I) strains from "Cuenca del Salado" (Argentina) and Uruguay clustered together. According to farm location, a clustering pattern for G6(IV)P[5] strains of beef farms was observed. Both G6 lineage strains together revealed an evolutionary rate of 1.24 × 10[-3] substitutions/site/year, and the time to the most recent common ancestor was dated in 1853. The most probable ancestral locations were Argentina in 1981 for G6(III) strains and the USA in 1940 for G6(IV) strains. The highest migration rates for both G6 lineages together were from Argentina to Brazil and Uruguay. Altogether, the epidemiology, genetic diversity, and phylogeny of RVA in calves can differ according to the production system and farm location. We provide novel knowledge about the evolutionary origin of a bovine G8P[11] strain. Finally, bovine G6 strains from American countries would have originated in the USA nearly a century before its first description.}, } @article {pmid37475479, year = {2023}, author = {Lawenius, L and Cowardin, C and Grahnemo, L and Scheffler, JM and Horkeby, K and Engdahl, C and Wu, J and Vandenput, L and Koskela, A and Tuukkanen, J and Coward, E and Hveem, K and Langhammer, A and Abrahamsson, S and Gordon, JI and Sjögren, K and Ohlsson, C}, title = {Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236755}, pmid = {37475479}, issn = {1949-0984}, mesh = {Young Adult ; Humans ; Mice ; Animals ; Aged ; Infant ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Aging ; Cecum ; }, abstract = {Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.}, } @article {pmid37895006, year = {2023}, author = {Kim, S and Noh, JH and Lee, MJ and Park, YJ and Kim, BM and Kim, YS and Hwang, S and Park, C and Kim, K}, title = {Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895006}, issn = {1422-0067}, support = {NRF- 2020R1A2C3004508//National Research Foundation of Korea/ ; }, mesh = {Rats ; Animals ; *Transcriptome ; Mitochondria/genetics/metabolism ; Gene Expression Profiling ; *Sepsis/genetics/metabolism ; }, abstract = {Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.}, } @article {pmid37894615, year = {2023}, author = {Ni, Z and Li, J and Qian, X and Yong, Y and Wu, M and Wang, Y and Lv, W and Zhang, S and Zhang, Y and Shao, Y and Chen, A}, title = {Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {20}, pages = {}, pmid = {37894615}, issn = {1420-3049}, support = {BY2022773//Jiangsu Province's industry university research cooperation project/ ; BY2022777//Jiangsu Province's industry university research cooperation project/ ; KC22477//Xuzhou Science and Technology Program/ ; }, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Dysbiosis/drug therapy/microbiology ; *Hyperglycemia/drug therapy ; Polysaccharides/pharmacology/therapeutic use ; }, abstract = {Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.}, } @article {pmid37894194, year = {2023}, author = {Lopetuso, LR and Laterza, L and Petito, V and Pecere, S and Quaranta, G and Del Chierico, F and Puca, P and Schiavoni, E and Napolitano, D and Poscia, A and Ianiro, G and Pugliese, D and Putignani, L and Sanguinetti, M and Armuzzi, A and Masucci, L and Gasbarrini, A and Cammarota, G and Scaldaferri, F}, title = {Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894194}, issn = {2076-2607}, abstract = {The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.}, } @article {pmid37894186, year = {2023}, author = {Beharry, KD and Latkowska, M and Valencia, AM and Allana, A and Soto, J and Cai, CL and Golombek, S and Hand, I and Aranda, JV}, title = {Factors Influencing Neonatal Gut Microbiome and Health with a Focus on Necrotizing Enterocolitis.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894186}, issn = {2076-2607}, abstract = {Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.}, } @article {pmid37894065, year = {2023}, author = {Martinelli, S and Nannini, G and Cianchi, F and Staderini, F and Coratti, F and Amedei, A}, title = {Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894065}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.}, } @article {pmid37894027, year = {2023}, author = {Napolitano, M and Fasulo, E and Ungaro, F and Massimino, L and Sinagra, E and Danese, S and Mandarino, FV}, title = {Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894027}, issn = {2076-2607}, abstract = {Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.}, } @article {pmid37892453, year = {2023}, author = {Wu, S and Wu, Z and Chen, Y}, title = {Effect of Cordyceps militaris Powder Prophylactic Supplementation on Intestinal Mucosal Barrier Impairment and Microbiota-Metabolites Axis in DSS-Injured Mice.}, journal = {Nutrients}, volume = {15}, number = {20}, pages = {}, pmid = {37892453}, issn = {2072-6643}, support = {82070543//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; 2021YFA0717001//National Key R&D Program of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Planning Project/ ; ZDSYS20220606100800002//Shenzhen Science and Technology Program/ ; }, mesh = {Humans ; Animals ; Mice ; *Cordyceps ; Powders ; *Microbiota ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/chemically induced/prevention & control ; *Food Ingredients ; Dietary Supplements ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; *Colitis ; Colon ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease with an unknown pathogenesis and increasing incidence. The objective of this study is to investigate the impact of prophylactic treatment with Cordyceps militaris on UC. The findings demonstrate that prophylactic supplementation of C. militaris powder effectively mitigates disease symptoms in DSS-injured mice, while also reducing the secretion of pro-inflammatory cytokines. Furthermore, C. militaris powder enhances the integrity of the intestinal mucosal barrier by up-regulating MUC2 protein expression and improving tight junction proteins (ZO-1, occludin, and claudin 1) in DSS-injured mice. Multiomics integration analyses revealed that C. militaris powder not only reshaped gut microbiota composition, with an increase in Lactobacillus, Odoribacter, and Mucispirillum, but also exerted regulatory effects on various metabolic pathways including amino acid, glyoxylates, dicarboxylates, glycerophospholipids, and arachidonic acid. Subsequent analysis further elucidated the intricate interplay of gut microbiota, the intestinal mucosal barrier, and metabolites, suggesting that the microbiota-metabolite axis may involve the effect of C. militaris on intestinal mucosal barrier repair in UC. Moreover, in vitro experiments demonstrated that peptides and polysaccharides, derived from C. militaris, exerted an ability to change the gut microbiota structure of UC patients' feces, particularly by promoting the growth of Lactobacillus. These findings suggest that regulatory properties of C. militaris on gut microbiota may underlie the potential mechanism responsible for the protective effect of C. militaris in UC. Consequently, our study will provide support for the utilization of C. militaris as a whole food-based ingredient against the occurrence and development of UC.}, } @article {pmid37885166, year = {2023}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Letter: A step forward towards a standard FMT protocol for IBS.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {10}, pages = {1115-1116}, doi = {10.1111/apt.17749}, pmid = {37885166}, issn = {1365-2036}, mesh = {Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome ; }, } @article {pmid37891616, year = {2023}, author = {Moreno, AF and Lavín-Alconero, L and de Ugarriza, PL and Blanco, LS and Hernández, SC and Burgués, JMB and de Miguel, MI and Huerta, AJG and Zarzuela, MP and Boluda, B and Humala, K and Calabuig, ML and Amigo, ML and Casas, MC and Del Mar García-Saiz, M and Verdugo, AF and Domínguez, JF and Bernal, T}, title = {FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety.}, journal = {Trials}, volume = {24}, number = {1}, pages = {694}, pmid = {37891616}, issn = {1745-6215}, support = {FIS PI21/01590//Instituto de Salud Carlos III/ ; }, abstract = {BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB.

METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed.

DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated.

TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 .

PROTOCOL VERSION: 3.0, dated 20 May 2022.}, } @article {pmid37888102, year = {2023}, author = {Kaltsas, A and Zachariou, A and Markou, E and Dimitriadis, F and Sofikitis, N and Pournaras, S}, title = {Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions.}, journal = {Journal of personalized medicine}, volume = {13}, number = {10}, pages = {}, pmid = {37888102}, issn = {2075-4426}, abstract = {The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors.}, } @article {pmid37887364, year = {2023}, author = {Jess, AT and Eskander, GH and Vu, MH and Michail, S}, title = {Short-Chain Fatty Acid Levels after Fecal Microbiota Transplantation in a Pediatric Cohort with Recurrent Clostridioides difficile Infection.}, journal = {Metabolites}, volume = {13}, number = {10}, pages = {}, pmid = {37887364}, issn = {2218-1989}, abstract = {Though antibiotics are the mainstay treatment for Clostridioides difficile, a large population of individuals infected will experience recurrence. In turn, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent C. difficile infection (rCDI). Mechanistically, by providing a healthy, diverse flora to the infected individual, FMT "resets" the underlying gut microbiome dysbiosis associated with rCDI. A proposed mechanism through which this occurs is via microbiome metabolites such as short-chain fatty acids (SCFAs); however, this has not been previously studied in pediatric patients. Using mass spectroscopy, we quantified pre- and post-transplant levels of acetate, isovalerate, butyrate, formate, and propionate in pediatric patients diagnosed with rCDI (n = 9). We compared pre- and post-transplant levels within the rCDI cohort at 1, 3, 6, and 12 months post-transplant and correlated these levels with healthy controls (n = 19). We witnessed a significant difference in the combined SCFA levels and the individual levels of acetate, butyrate, isovalerate, and propionate in the pre-treatment rCDI cohort compared to the healthy controls. In addition, there was a significant increase in combined SCFA levels at 12 months post-transplant within the rCDI group compared to that of their pre-transplant levels, and, more specifically, acetate, propionate, and isovalerate increased from pre-transplant to 12 months post-transplant. The longitudinal aspect of this study allowed us to identify mechanisms that contribute to the durability of responses to FMT, as well as characterize the unique patterns of short-chain fatty acid level recovery in rCDI pediatric patients.}, } @article {pmid37887204, year = {2023}, author = {Pang, J and Beyi, AF and Looft, T and Zhang, Q and Sahin, O}, title = {Fecal Microbiota Transplantation Reduces Campylobacter jejuni Colonization in Young Broiler Chickens Challenged by Oral Gavage but Not by Seeder Birds.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, doi = {10.3390/antibiotics12101503}, pmid = {37887204}, issn = {2079-6382}, support = {2018-67017-28117//United States Department of Agriculture/ ; }, abstract = {Campylobacter spp., particularly C. jejuni and C. coli, are major food safety concerns, transmitted to humans mainly via contaminated poultry meat. In a previous study, we found that some commercial broiler farms consistently produced Campylobacter-free flocks while others consistently reared Campylobacter-colonized flocks, and significant differences in the gut microbiota compositions between the two types of farm categories were revealed. Therefore, we hypothesized that gut microbiota influences Campylobacter colonization in poultry and that the microbiota from Campylobacter-free flocks may confer colonization resistance to Campylobacter in the chicken intestine. In this study, two fecal microbiota transplantation (FMT) trials were performed to test the hypothesis. Newly hatched chicks were given FMT via oral gavage of the cecal content of Campylobacter-free adult chickens (treatment groups) or PBS (control groups) before the feed consumption. Approximately two weeks after the FMT, the birds were challenged with C. jejuni either by oral gavage (trial 1) or by co-mingling with Campylobacter-colonized seeder birds (trial 2) to evaluate the potential protective effect of the FMT. Cecal contents were collected (3 times, 5 days apart) to determine the Campylobacter colonization levels via culture and microbiota compositions via 16S rRNA gene sequencing. FMT reduced cecal Campylobacter colonization significantly (log10 1.2-2.54 CFU/g) in trial 1 but not in trial 2, although FMT significantly impacted the diversity and compositions of the gut microbiota in both trials. Several genera, such as Butyricimonas, Parabacteroides, Parasutterella, Bilophila, Fournierella, Phascolarctobacterium, and Helicobacter, had increased abundance in the FMT-treated groups in both trials. Furthermore, Campylobacter abundance was found to be negatively correlated with the Escherichia and Ruminococcus_torques_group genera. These findings indicate that even though FMT with adult cecal microbiota can positively affect the subsequent development of the gut microbiota in young broilers, its inhibitory effect on Campylobacter colonization varies and appears to be influenced by the challenge models.}, } @article {pmid37879794, year = {2023}, author = {Liu, Y and Wu, H and Wang, T and Shi, X and He, H and Huang, H and Yang, Y and Dai, M}, title = {Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {759-774}, doi = {10.1016/S1875-5364(23)60506-0}, pmid = {37879794}, issn = {1875-5364}, mesh = {Mice ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Reactive Oxygen Species ; Endothelial Cells ; Inflammation/drug therapy ; *Atherosclerosis/drug therapy ; Mice, Inbred C57BL ; Diet, High-Fat ; }, abstract = {Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE[-/-] mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg[-1]) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.}, } @article {pmid37879793, year = {2023}, author = {Zhou, J and Fan, Q and Cai, X and Zhang, Y and Hou, Y and Cao, S and Li, Z and Feng, M and Wang, Q and Zhang, J and Wang, G and Zheng, X and Hao, H}, title = {Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {745-758}, doi = {10.1016/S1875-5364(23)60496-0}, pmid = {37879793}, issn = {1875-5364}, mesh = {Humans ; Mice ; Animals ; *Depression/drug therapy ; *Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba ; }, abstract = {Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.}, } @article {pmid37873265, year = {2023}, author = {Chang, D and Gupta, VK and Hur, B and Cobo-López, S and Cunningham, KY and Han, NS and Lee, I and Kronzer, VL and Teigen, LM and Karnatovskaia, LV and Longbrake, EE and Davis, JM and Nelson, H and Sung, J}, title = {Gut Microbiome Wellness Index 2 for Enhanced Health Status Prediction from Gut Microbiome Taxonomic Profiles.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.30.560294}, pmid = {37873265}, abstract = {Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level α-diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individual's unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.}, } @article {pmid37872499, year = {2023}, author = {Skjevling, LK and Hanssen, HM and Valle, PC and Goll, R and Juul, FE and Arlov, Ø and Johnsen, PH}, title = {Colonic distribution of FMT by different enema procedures compared to colonoscopy - proof of concept study using contrast fluid.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {363}, pmid = {37872499}, issn = {1471-230X}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Colon/diagnostic imaging ; Colonoscopy ; Cross-Over Studies ; Enema ; Fecal Microbiota Transplantation/methods ; Feces ; Proof of Concept Study ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent Clostridioides difficile infections and is under investigation as a treatment for several other diseases. FMT's mechanism of action is assumed to be through alterations of the colon microbiota. FMT can be delivered by several methods, but few studies have directly compared how FMT is distributed in the colon by different methods. Specifically, the proximal distribution of FMT delivered by enema is unknown.

METHODS: In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema ÷) and after (enema +) the positioning procedure.

CONCLUSION: Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema ÷). There were no adverse events.

INTERPRETATION: This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness.

TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021).}, } @article {pmid37872356, year = {2023}, author = {Jadhav, G and Dudhabhate, BB and Kokare, DM and Sakharkar, AJ}, title = {Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37872356}, issn = {1559-1182}, support = {RUSA-CBS-TH 4.5//Rashtriya Uchchatar Shiksha Abhiyan/ ; CRG/2020/004971//Science and Engineering Research Board (IN), SERB/ ; }, abstract = {Gut microbiota serves in the development and maintenance of phenotype. However, the underlying mechanisms are still in its infancy. The current study shows epigenetic remodelling in the brain as a causal mechanism in the gut microbiota-brain axis. Like in trauma patients, gut dysbiosis and anxiety were comorbid in adult male Wistar rats subjected to repeated mild traumatic brain injuries (rMTBI). rMTBI caused epigenetic dysregulation of brain-derived neurotrophic factor (Bdnf) expression in the amygdala, owing to the formation of transcriptional co-repressor complex due to dynamic interaction between histone deacetylase and DNA methylation modification at the Bdnf gene promoter. The probiosis after faecal microbiota transplantation (FMT) from healthy naïve rats or by administration of single strain probiotic (SSP), Lactobacillus rhamnosus GG (LGG), recuperated rMTBI-induced anxiety. Concurrently, LGG infusion or naïve FMT also dislodged rMTBI-induced co-repressor complex resulting in the normalization of Bdnf expression and neuronal plasticity as measured by Golgi-Cox staining. Furthermore, sodium butyrate, a short-chain fatty acid, produced neurobehavioural effects similar to naïve FMT or LGG administration. Interestingly, the gut microbiota from rMTBI-exposed rats per se was able to provoke anxiety in naïve rats in parallel with BDNF deficits. Therefore, gut microbiota seems to be causally linked with the chromatin remodelling necessary for neuroadaptations via neuronal plasticity which drives experience-dependent behavioural manifestations.}, } @article {pmid37871256, year = {2023}, author = {Peled, JU and van den Brink, MRM}, title = {Fecal Transplantation in Hematopoietic Transplantation.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2301169}, doi = {10.1200/JCO.23.01169}, pmid = {37871256}, issn = {1527-7755}, } @article {pmid37870235, year = {2023}, author = {Duan, R and von Ehrlich-Treuenstätt, VH and Kakoschke, SC and Schardey, J and Wirth, U and Albertsmeier, M and Renz, BW and Andrassy, J and Bazhin, AV and Hodin, R and Werner, J and Ilmer, M and Kühn, F}, title = {Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.}, journal = {Journal of the American College of Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1097/XCS.0000000000000879}, pmid = {37870235}, issn = {1879-1190}, abstract = {BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function, intestinal homeostasis, and prevents endotoxemia by detoxifying lipopolysaccharides (LPS). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significant stronger decrease in IAP than other major abdominal surgery.

STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD as well as other major surgical procedures without duodenectomy. Samples were analyzed using enzyme histochemistry, the para-nitrophenyl phosphate (pNPP) method for IAP, and limulus amebocyte lysate (LAL) assay for LPS.

RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p< 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p=0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP - also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p=0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p=0.0062) and more prominent in pancreatic cancer (p = 0.0009).

CONCLUSION: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.}, } @article {pmid37868345, year = {2023}, author = {Yuan, C and He, Y and Xie, K and Feng, L and Gao, S and Cai, L}, title = {Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1282431}, pmid = {37868345}, issn = {2235-2988}, abstract = {The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.}, } @article {pmid37867202, year = {2023}, author = {Ma, J and Wen, S and Dong, A and Fan, W and Kang, Y}, title = {Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2300566}, doi = {10.1002/mnfr.202300566}, pmid = {37867202}, issn = {1613-4133}, support = {202103021223240//Natural Science Foundation of Shanxi Province for Youths/ ; SD2009//Science Research Start-up Fund of Shanxi Province for Doctors/ ; XD2014//Science Research Start-up Fund of Shanxi Medical University for Doctor/ ; 2021L217//Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi/ ; }, abstract = {Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.}, } @article {pmid37865904, year = {2023}, author = {Clifford, T}, title = {Practice Corner: Fecal Microbiota Transplant.}, journal = {Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jopan.2023.08.011}, pmid = {37865904}, issn = {1532-8473}, } @article {pmid37865177, year = {2023}, author = {Guha, L and Agnihotri, TG and Jain, A and Kumar, H}, title = {Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches.}, journal = {Life sciences}, volume = {334}, number = {}, pages = {122193}, doi = {10.1016/j.lfs.2023.122193}, pmid = {37865177}, issn = {1879-0631}, abstract = {Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.}, } @article {pmid37863204, year = {2023}, author = {Guan, Y and Liu, T and Xu, F and Xie, S and Gu, W and Bie, Y}, title = {Integration of 16S rRNA gene sequencing and LC/MS-based metabolomic analysis of early biomarkers of acute stroke in Tibetan miniature pigs.}, journal = {Journal of microbiological methods}, volume = {}, number = {}, pages = {106846}, doi = {10.1016/j.mimet.2023.106846}, pmid = {37863204}, issn = {1872-8359}, abstract = {Acute ischaemic stroke (AIS) is a complex, systemic, pathological, and physiological process. Systemic inflammatory responses and disorders of the gut microbiome contribute to increased mortality and disability following AIS. We conducted 16S high-throughput sequencing and ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry-based non-targeted metabolomic analyses of the plasma from a Tibetan miniature pig middle cerebral artery occlusion (MCAO) model. A significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Actinobacteria were observed after the onset of AIS. Among the plasma metabolites, the levels of phospholipids and amino acids were considerably altered. Loading values and differential metabolite-bacterial group association analyses of the metabolome and microbiome indicated a correlation between the microbiome and metabolome of Tibetan miniature pigs after MCAO. Furthermore, significant changes were observed in the ABC transporter pathway and purine metabolism in the gut microbiome-plasma metabolome during the early stage of AIS. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis showed that arginine, proline, and cyanoamino acid metabolism was upregulated while ABC transporter metabolism pathway and carbohydrate digestion and absorption were substantially downregulated. The results of this study suggest that AIS affects the gut microbiota and plasma metabolites in Tibetan miniature pigs and that faecal microbiota transplantation could be a potential therapeutic approach for AIS.}, } @article {pmid37862466, year = {2023}, author = {Diaz, LA and Winder, GS and Leggio, L and Bajaj, JS and Bataller, R and Arab, JP}, title = {New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000645}, pmid = {37862466}, issn = {1527-3350}, abstract = {Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for AUD. In particular, a change in gut microbiota composition and function, especially bile acid homeostasis, and these changes can improve after alcohol cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors in turn promote liver and brain inflammation and progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, e.g.: the ghrelin system (ghrelin receptor blockade), incretin mimetics (GLP-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of AUD. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-related burden of disease.}, } @article {pmid37860535, year = {2023}, author = {Ma, L and Song, J and Chen, X and Dai, D and Chen, J and Zhang, L}, title = {Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.}, journal = {Heliyon}, volume = {9}, number = {10}, pages = {e20591}, pmid = {37860535}, issn = {2405-8440}, abstract = {OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH.

METHODS: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues.

RESULTS: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-β cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner.

CONCLUSION: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.}, } @article {pmid37858797, year = {2023}, author = {Yang, J and Wei, H and Lin, Y and Chu, ES and Zhou, Y and Gou, H and Guo, S and Lau, HC and Cheung, AH and Chen, H and To, KF and Sung, JJ and Wang, Y and Yu, J}, title = {High soluble fiber promotes colorectal tumorigenesis through modulating gut microbiota and metabolites in mice.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.10.012}, pmid = {37858797}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice.

METHODS: Apc[min/+] mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively.

RESULTS: Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apc[min/+] mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apc[min/+] mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied with increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice.

CONCLUSION: High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.}, } @article {pmid37858192, year = {2023}, author = {Zhong, HJ and Xie, X and Chen, WJ and Zhuang, YP and Hu, X and Cai, YL and Zeng, HL and Xiao, C and Li, Y and Ding, Y and Xue, L and Chen, M and Zhang, J and Wu, Q and He, XX}, title = {Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {740}, pmid = {37858192}, issn = {1479-5876}, support = {2022B1111070006//Guangdong Science and Technology Department/ ; 2021M700034//Postdoctoral Research Foundation of China/ ; 2021KCXTD025//Department of Education of Guangdong Province/ ; }, mesh = {Humans ; Retrospective Studies ; Kidney/metabolism ; *Renal Insufficiency, Chronic/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.

METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.

RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05).

CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.}, } @article {pmid37857731, year = {2023}, author = {Bahar Halpern, K and Korem Kohanim, Y and Biram, A and Harnik, Y and Egozi, A and Yakubovsky, O and Shulman, Z and Itzkovitz, S}, title = {The cellular states and fates of shed intestinal cells.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {37857731}, issn = {2522-5812}, abstract = {The intestinal epithelium is replaced every few days[1]. Enterocytes are shed into the gut lumen predominantly from the tips of villi[2,3] and have been believed to rapidly die upon their dissociation from the tissue[4,5]. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.}, } @article {pmid37857710, year = {2023}, author = {Riwes, MM and Golob, JL and Magenau, J and Shan, M and Dick, G and Braun, T and Schmidt, TM and Pawarode, A and Anand, S and Ghosh, M and Maciejewski, J and King, D and Choi, S and Yanik, G and Geer, M and Hillman, E and Lyssiotis, CA and Tewari, M and Reddy, P}, title = {Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {37857710}, issn = {1546-170X}, support = {P01 HL149633/HL/NHLBI NIH HHS/United States ; P01 HL149633/HL/NHLBI NIH HHS/United States ; P01 HL149633/HL/NHLBI NIH HHS/United States ; }, abstract = {Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day -7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they were not (P < 0.0001). An exploratory objective was to evaluate plasma metabolites. We observed longitudinal changes in plasma metabolites compared to baseline, which were independent of RPS (P < 0.0001). However, in recipients of RPS, the dominant plasma metabolites were more stable compared to historical controls with significant difference at engraftment (P < 0.05). These results indicate that RPS in recipients of allogeneic HCT is feasible; in this study, it was associated with significant alterations in intestinal and plasma metabolites. A phase 2 trial examining the effect of RPS on graft-versus-host disease in recipients of allogeneic HCT is underway. ClinicalTrials.gov registration: NCT02763033 .}, } @article {pmid37857552, year = {2023}, author = {Chen, Z and Lv, M and Liang, J and Yang, K and Li, F and Zhou, Z and Qiu, M and Chen, H and Cai, Z and Cui, W and Li, Z}, title = {Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2303015}, doi = {10.1002/advs.202303015}, pmid = {37857552}, issn = {2198-3844}, support = {81871090//National Natural Science Foundation of China/ ; 32171340//National Natural Science Foundation of China/ ; 32101104//National Natural Science Foundation of China/ ; 2020YFA0908200//National Key Research and Development Program of China/ ; 202140127//Shanghai Municipal Health Planning Commission/ ; }, abstract = {Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.}, } @article {pmid37856155, year = {2023}, author = {Cheng, J and Liu, D and Huang, Y and Chen, L and Li, Y and Yang, Z and Fu, S and Hu, G}, title = {Phlorizin Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota and Inhibiting Ferroptosis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c01497}, pmid = {37856155}, issn = {1520-5118}, abstract = {Phlorizin (PHZ) is the main active component of apple peel and presents a potential application value. In the past few years, some reports have suggested that PHZ may have antioxidant and anti-inflammatory effects. Herein, we have attempted to assess the protective effects of PHZ on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the underlying molecular mechanisms. Our results suggested that early intervention with PHZ (20, 40, and 80 mg/kg) significantly reduced the severity of DSS-induced colitis in mice, as presented by a longer colon, improved tight junction protein, decreased disease activity index, and attenuated inflammatory factors. Additionally, early intervention with + (20, 40, and 80 mg/kg) significantly inhibited ferroptosis by decreasing the surrogate ferroptosis marker levels (MDA and Iron Content). Additionally, PHZ (80 mg/kg) increased the diversity of intestinal flora in colitic mice by elevating the levels of beneficial bacteria (Lactobacillaceae and Muribaculaceae) and reducing the levels of harmful bacteria (Lachnospiraceae). This indirectly led to an increase in the amount of short-chain fatty acids. A fecal microbial transplantation (FMT) test was conducted to show that PHZ (80 mg/kg) ameliorated ulcerative colitis (UC) by regulating gut dysbiosis. In conclusion, early intervention with PHZ decreased DSS-induced colitis in mice by preserving their intestinal barrier and regulating their intestinal flora.}, } @article {pmid37854336, year = {2023}, author = {Guo, C and Zhang, P and Li, J and Zhou, C and Yang, Z and Zhang, Y and Luo, Y and Zhou, J and Cai, Y and Ming, Y}, title = {The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1276404}, pmid = {37854336}, issn = {1664-302X}, abstract = {BACKGROUND: The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis.

METHODS: A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, α and β diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis.

RESULTS: Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the α and β diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection.

CONCLUSION: The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.}, } @article {pmid37852131, year = {2023}, author = {Fang, G and Wang, S and Chen, Q and Luo, H and Lian, X and Shi, D}, title = {Time-restricted feeding affects the fecal microbiome metabolome and its diurnal oscillations in lung cancer mice.}, journal = {Neoplasia (New York, N.Y.)}, volume = {45}, number = {}, pages = {100943}, doi = {10.1016/j.neo.2023.100943}, pmid = {37852131}, issn = {1476-5586}, abstract = {The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.}, } @article {pmid37851840, year = {2023}, author = {Zhang, Z and Cheng, N and Liang, J and Deng, Y and Xiang, P and Hei, Z and Li, X}, title = {Gut microbiota changes in animal models of spinal cord injury: a preclinical systematic review and meta-analysis.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2269379}, pmid = {37851840}, issn = {1365-2060}, abstract = {BACKGROUND: An increasing number of studies show that the intestinal flora is closely related to spinal cord injury. Many researchers are exploring the changes in the richness, diversity, and evenness of intestinal flora in spinal cord injury animal models to identify the characteristic bacteria.

METHODS: A comprehensive literature search was conducted using three databases: PubMed, Embase, and Web of Science. A meta-analysis was performed using R 4.3.1 to evaluate the comparison of microbiota diversity, richness, and evenness and the relative abundance of intestinal microbiota in animals with spinal cord injury and blank controls.

RESULTS: Fifteen studies were included in the meta-analysis, of which 12 involved gut microbiota distribution indicators and 11 included intestinal microflora relative abundance indicators. Meta-analysis of high-dimensional indicators describing the distribution of the gut microbiota identified a substantial decline in the evenness and richness of the intestinal flora. In addition, the Actinobacteria phylum and Erysipelotrichales and Clostridiales orders were significantly different between the spinal cord injury and sham groups; therefore, they may be the characteristic bacteria in spinal cord injury models.

CONCLUSION: Our meta-analysis suggested that the gut microbiota in the spinal cord injury animal model group was altered compared with that in the control group, with varying degrees of changes in richness and evenness and potentially pathogenic characteristic flora. More rigorous methodological studies are needed because of the high heterogeneity and limited sample size. Further research is needed to clinically apply intestinal microbiota and potentially guide fecal microbiota transplantation therapy.}, } @article {pmid37851313, year = {2023}, author = {Pan, I and Issac, PK and Rahman, MM and Guru, A and Arockiaraj, J}, title = {Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37851313}, issn = {1559-1182}, abstract = {Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.}, } @article {pmid37849493, year = {2023}, author = {Lan, KY and Le, PH and Chiu, CT and Chen, CC and Yeh, YM and Cheng, HT and Kuo, CJ and Chen, CL and Chen, YC and Yeh, PJ and Chiu, CH and Chang, CJ}, title = {Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1229148}, pmid = {37849493}, issn = {2296-858X}, abstract = {BACKGROUND: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD.

METHODS: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan.

RESULTS: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI.

CONCLUSION: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.}, } @article {pmid37849266, year = {2023}, author = {Cui, JQ and Tian, HL and Wang, XJ and Wang, L and Liu, YK and Ye, C and Ding, LF and Li, N and Chen, QY}, title = {[Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {26}, number = {10}, pages = {955-962}, doi = {10.3760/cma.j.cn441530-20230816-00052}, pmid = {37849266}, issn = {1671-0274}, support = {202240177//Shanghai Health Commission's Surface Project/ ; }, mesh = {Female ; Humans ; Male ; Middle Aged ; Abdominal Pain/complications ; China ; Diarrhea ; *Enteritis/etiology/therapy ; *Fecal Microbiota Transplantation/methods ; Flatulence/complications ; Hemoglobins ; *Intestinal Obstruction/etiology/surgery ; *Nutritional Support ; Postoperative Complications ; Prealbumin ; Prospective Studies ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Adult ; *Radiotherapy/adverse effects ; }, abstract = {Objective: To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction. Methods: The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42-65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien-Dindo classification of surgical complications (I-V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0-144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results: Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups (P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant (P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values (F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points (P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation (F=5.514, P=0.002), but not in the conventional, group (F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion: Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.}, } @article {pmid37849234, year = {2023}, author = {Grabrucker, S and Marizzoni, M and Silajdžić, E and Lopizzo, N and Mombelli, E and Nicolas, S and Dohm-Hansen, S and Scassellati, C and Moretti, DV and Rosa, M and Hoffmann, K and Cryan, JF and O'Leary, OF and English, JA and Lavelle, A and O'Neill, C and Thuret, S and Cattaneo, A and Nolan, YM}, title = {Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awad303}, pmid = {37849234}, issn = {1460-2156}, support = {MR/S00484X/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.}, } @article {pmid37846600, year = {2023}, author = {Li, Y and Liu, Q and Zhang, L and Zou, J and He, R and Zhou, Y and Qian, C and Zhu, Y and Chen, R and Zhang, Y and Cai, P and Wang, M and Shao, W and Ji, M and Wu, H and Zhang, F and Liu, Z and Liu, Y}, title = {Washed microbiota transplantation reduces glycemic variability in unstable diabetes.}, journal = {Journal of diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1111/1753-0407.13485}, pmid = {37846600}, issn = {1753-0407}, support = {2022YFA0806103//National Key R&D Program of China/ ; 81770778//National Natural Science Foundation of China/ ; 81800724//National Natural Science Foundation of China/ ; 81800735//National Natural Science Foundation of China/ ; 82070849//National Natural Science Foundation of China/ ; 82270871//National Natural Science Foundation of China/ ; BK20180672//Natural Science Foundation of Jiangsu Province/ ; 18KJB310005//Natural Science Foundation of the Jiangsu Higher Education Institutions/ ; BE2022794//the Jiangsu Provincial Key Research Development Program/ ; }, abstract = {BACKGROUND: Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes.

METHODS: Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms.

RESULTS: Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide.

CONCLUSIONS: WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.}, } @article {pmid37842639, year = {2023}, author = {Patra, D and Banerjee, D and Ramprasad, P and Roy, S and Pal, D and Dasgupta, S}, title = {Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1224982}, pmid = {37842639}, issn = {2296-889X}, abstract = {An imbalance in microbial homeostasis, referred to as dysbiosis, is critically associated with the progression of obesity-induced metabolic disorders including type 2 diabetes (T2D). Alteration in gut microbial diversity and the abundance of pathogenic bacteria disrupt metabolic homeostasis and potentiate chronic inflammation, due to intestinal leakage or release of a diverse range of microbial metabolites. The obesity-associated shifts in gut microbial diversity worsen the triglyceride and cholesterol level that regulates adipogenesis, lipolysis, and fatty acid oxidation. Moreover, an intricate interaction of the gut-brain axis coupled with the altered microbiome profile and microbiome-derived metabolites disrupt bidirectional communication for instigating insulin resistance. Furthermore, a distinct microbial community within visceral adipose tissue is associated with its dysfunction in obese T2D individuals. The specific bacterial signature was found in the mesenteric adipose tissue of T2D patients. Recently, it has been shown that in Crohn's disease, the gut-derived bacterium Clostridium innocuum translocated to the mesenteric adipose tissue and modulates its function by inducing M2 macrophage polarization, increasing adipogenesis, and promoting microbial surveillance. Considering these facts, modulation of microbiota in the gut and adipose tissue could serve as one of the contemporary approaches to manage T2D by using prebiotics, probiotics, or faecal microbial transplantation. Altogether, this review consolidates the current knowledge on gut and adipose tissue dysbiosis and its role in the development and progression of obesity-induced T2D. It emphasizes the significance of the gut microbiota and its metabolites as well as the alteration of adipose tissue microbiome profile for promoting adipose tissue dysfunction, and identifying novel therapeutic strategies, providing valuable insights and directions for future research and potential clinical interventions.}, } @article {pmid37842346, year = {2023}, author = {Warraich, F and Sohail, SH and Knee, A and Smith, J and Schlecht, H and Skiest, D}, title = {Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45118}, pmid = {37842346}, issn = {2168-8184}, abstract = {Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI. Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018. We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.}, } @article {pmid37842104, year = {2023}, author = {Quattrini, C and Bozorgmanesh, R and Egli, P and Magdesian, KG}, title = {Fecal microbiota transplant for treatment of diarrhea in adult hospitalized horses-111 cases (2013-2018).}, journal = {Open veterinary journal}, volume = {13}, number = {9}, pages = {1135-1140}, pmid = {37842104}, issn = {2218-6050}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is increasingly administered as part of the treatment of colitis in horses, yet there is little data as to its effectiveness.

AIM: Retrospective evaluation of the effects of FMT on discharge status, fecal consistency, length of hospitalization, and improvement in clinical signs in horses hospitalized for diarrhea.

METHODS: Retrospective case-control study. Medical records of adult horses (>1 year old) that received at least one transfaunation treatment (2013-2018) in two referral hospitals were identified through a medical records database search. Medical records of contemporary adult horses with diarrhea who did not receive FMT at the same study centers were used as controls.

RESULTS: Control horses had statistically significant shorter hospitalization [7 (1-21)] as compared to the transfaunation group [12 (3-31)] (p = 0.0006). There were no significant differences between groups in the number of days to the improvement of feces (p = 0.38), or in days to normalization of fecal consistency (p = 0.43), respiratory rate (p = 0.42), heart rate (p = 0.27), body temperature (p = 0.12), peripheral white blood cell count (p = 0.37), improvement in appetite (p = 0.81), or attitude (p = 0.06). There was also no significant difference in survival to discharge (transfaunation 28/37, 75.7%; control 56/74, 75.7%, p = 1.0).

CONCLUSION: There were no significant advantages of performing FMTs in horses with diarrhea in this retrospective study. This highlights the need for prospective, randomized studies to evaluate the efficacy of FMT, as well as different formulations, in horses with colitis before this can become standard practice.}, } @article {pmid37841750, year = {2023}, author = {Huang, J and Gong, C and Zhou, A}, title = {Modulation of gut microbiota: a novel approach to enhancing the effects of immune checkpoint inhibitors.}, journal = {Therapeutic advances in medical oncology}, volume = {15}, number = {}, pages = {17588359231204854}, pmid = {37841750}, issn = {1758-8340}, abstract = {Although immune checkpoint inhibitors (ICIs) have greatly improved the prognosis of some cancer patients, the majority still fail to respond adequately, and the available biomarkers cannot reliably predict drug efficacy. The gut microbiota has received widespread attention among the various intrinsic and extrinsic factors contributing to drug resistance. As an essential regulator of physiological function, the impact of gut microbiota on host immunity and response to cancer therapy is increasingly recognized. Several studies have demonstrated significant differences in gut microbiota between responders and nonresponders. The gut microbiota associated with better clinical outcomes is called 'favorable gut microbiota'. Significantly, interventions can alter the gut microbiota. By shifting the gut microbiota to the 'favorable' one through various modifications, preclinical and clinical studies have yielded more pronounced responses and better clinical outcomes when combined with ICIs treatment, providing novel approaches to improve the efficacy of cancer immunotherapy. These findings may be attributed to the effects of gut microbiota and its metabolites on the immune microenvironment and the systemic immune system, but the underlying mechanisms remain to be discovered. In this review, we summarize the clinical evidence that the gut microbiota is strongly associated with the outcomes of ICI treatment and describe the gut microbiota characteristics associated with better clinical outcomes. We then expand on the current prevalent modalities of gut microbiota regulation, provide a comprehensive overview of preclinical and clinical research advances in improving the therapeutic efficacy and prognosis of ICIs by modulating gut microbiota, and suggest fundamental questions we need to address and potential directions for future research expansion.}, } @article {pmid37841685, year = {2023}, author = {Fagan, MM and Welch, CB and Scheulin, KM and Sneed, SE and Jeon, JH and Golan, ME and Cheek, SR and Barany, DA and Oeltzschner, G and Callaway, TR and Zhao, Q and Park, HJ and Lourenco, JM and Duberstein, KJ and West, FD}, title = {Fecal microbial transplantation limits neural injury severity and functional deficits in a pediatric piglet traumatic brain injury model.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1249539}, pmid = {37841685}, issn = {1662-4548}, abstract = {Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Due to bidirectional communication between the brain and gut microbial population, introduction of key gut bacteria may mitigate critical TBI-induced secondary injury cascades, thus lessening neural damage and improving functional outcomes. The objective of this study was to determine the efficacy of a daily fecal microbial transplant (FMT) to alleviate neural injury severity, prevent gut dysbiosis, and improve functional recovery post TBI in a translational pediatric piglet model. Male piglets at 4-weeks of age were randomly assigned to Sham + saline, TBI + saline, or TBI + FMT treatment groups. A moderate/severe TBI was induced by controlled cortical impact and Sham pigs underwent craniectomy surgery only. FMT or saline were administered by oral gavage daily for 7 days. MRI was performed 1 day (1D) and 7 days (7D) post TBI. Fecal and cecal samples were collected for 16S rRNA gene sequencing. Ipsilateral brain and ileum tissue samples were collected for histological assessment. Gait and behavior testing were conducted at multiple timepoints. MRI showed that FMT treated animals demonstrated decreased lesion volume and hemorrhage volume at 7D post TBI as compared to 1D post TBI. Histological analysis revealed improved neuron and oligodendrocyte survival and restored ileum tissue morphology at 7D post TBI in FMT treated animals. Microbiome analysis indicated decreased dysbiosis in FMT treated animals with an increase in multiple probiotic Lactobacilli species, associated with anti-inflammatory therapeutic effects, in the cecum of the FMT treated animals, while non-treated TBI animals showed an increase in pathogenic bacteria, associated with inflammation and disease such in feces. FMT mediated enhanced cellular and tissue recovery resulted in improved motor function including stride and step length and voluntary motor activity in FMT treated animals. Here we report for the first time in a highly translatable pediatric piglet TBI model, the potential of FMT treatment to significantly limit cellular and tissue damage leading to improved functional outcomes following a TBI.}, } @article {pmid37841431, year = {2023}, author = {Wang, Y and Han, W and Wang, N and Han, M and Ban, M and Dai, J and Dong, Y and Sun, T and Xu, J}, title = {The role of microbiota in the development and treatment of gastric cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1224669}, pmid = {37841431}, issn = {2234-943X}, abstract = {The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.}, } @article {pmid37841129, year = {2023}, author = {Li, MY and Duan, JQ and Wang, XH and Liu, M and Yang, QY and Li, Y and Cheng, K and Liu, HQ and Wang, F}, title = {Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora.}, journal = {ACS omega}, volume = {8}, number = {40}, pages = {36729-36743}, pmid = {37841129}, issn = {2470-1343}, abstract = {Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase β/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.}, } @article {pmid37840733, year = {2023}, author = {Hua, F and Cui, E and Lv, L and Wang, B and Li, L and Lu, H and Chen, N and Chen, W}, title = {Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1243102}, pmid = {37840733}, issn = {1664-302X}, abstract = {INTRODUCTION: Acute lung injury (ALI) is a severe respiratory tract disorder facilitated by dysregulated inflammation, oxidative stress and intestinal ecosystem. Fecal microbiota transplantation (FMT) is a rapid method for gut microbiota (GM) reconstruction. Furthermore, our previous studies have confirmed that human umbilical cord mesenchymal stromal cells (HUC-MSCs) can alleviate ALI by improving GM composition. Therefore, we aimed to explore the efficacy and mechanism of FMT from HUC-MSCs-treated mice on ALI.

METHODS: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-κB pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution.

RESULTS: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-κB pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group.

CONCLUSION: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-κB and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.}, } @article {pmid37840104, year = {2023}, author = {Jayachandran, M and Qu, S}, title = {Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies.}, journal = {Reviews in endocrine & metabolic disorders}, volume = {}, number = {}, pages = {}, pmid = {37840104}, issn = {1573-2606}, support = {2018YFC1314101//The National Key R&D Program of China/ ; 2016YFC1305600//The National Key R&D Program of China/ ; 81970677//National Natural Science Foundation of China/ ; 82170861//National Natural Science Foundation of China/ ; 22120190210//Fundamental Research Funds for the Central Universities of Tongji University/ ; SHDC2020CR1017B//Clinical Research Plan of SHDC/ ; 19DZ1910200//Shanghai Committee of Science and Technology, China/ ; 17DZ1910603//Shanghai Committee of Science and Technology, China/ ; 18411951803//Shanghai Committee of Science and Technology, China/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It's also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world's population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota's potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.}, } @article {pmid37839834, year = {2023}, author = {Yang, Y and Lv, L and Shi, S and Cai, G and Yu, L and Xu, S and Zhu, T and Su, X and Mao, N and Zhang, Y and Peng, S and He, J and Liu, Z and Wang, D}, title = {Polysaccharide from walnut green husk alleviates liver inflammation and gluconeogenesis dysfunction by altering gut microbiota in ochratoxin A-induced mice.}, journal = {Carbohydrate polymers}, volume = {322}, number = {}, pages = {121362}, doi = {10.1016/j.carbpol.2023.121362}, pmid = {37839834}, issn = {1879-1344}, abstract = {Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Galp-(1→, α-D-Galp (1→, and →2)-α-L-Rhap-(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota.}, } @article {pmid37839771, year = {2023}, author = {Wang, C and Jiang, S and Zheng, H and An, Y and Zheng, W and Zhang, J and Liu, J and Lin, H and Wang, G and Wang, F}, title = {Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {117294}, doi = {10.1016/j.jep.2023.117294}, pmid = {37839771}, issn = {1872-7573}, abstract = {Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined.

AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism.

MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease.

RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats.

CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.}, } @article {pmid37839469, year = {2023}, author = {Tao, Y and Zhou, H and Li, Z and Wu, H and Wu, F and Miao, Z and Shi, H and Huang, F and Wu, X}, title = {TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis.}, journal = {Journal of affective disorders}, volume = {344}, number = {}, pages = {219-232}, doi = {10.1016/j.jad.2023.10.072}, pmid = {37839469}, issn = {1573-2517}, abstract = {BACKGROUND AND PURPOSE: Anxiety and depression have been associated with imbalances in the gut microbiota and bile acid metabolism. Takeda G protein-coupled receptor 5 (TGR5), a bile acid receptor involved in metabolism, is influenced by the gut microbiota. This study aimed to investigate the relationship between anxiety, depression, and microbiota using TGR5 knockout mice.

METHODS: We employed the following methods: (1) Assessment of behavioral changes, (2) Measurement of 5-HT levels and protein expression, (3) Analysis of stool samples, (4) Utilization of gene sequencing and statistical analysis to identify microbial signatures, (5) Examination of correlations between microbial signatures and 5-HT levels, and (6) Fecal microbiota transplantation experiments of TGR5[-/-] mice.

RESULTS: The deletion of TGR5 was found to result in increased anxiety- and depression-like behaviors in mice. TGR5 knockout mice exhibited significant reductions in 5-hydroxytryptamine (5-HT) levels in both serum and hippocampus, accompanied by a decrease in the expression of 5-HT1A receptor in the hippocampus. Moreover, TGR5 deficiency was associated with a decrease in the species richness of the gut microbiota. Specifically, the gut microbiota compositions of TGR5 knockout mice displayed distinct differences compared to their littermates, characterized by higher abundances of Anaeroplasma, Prevotella, Staphylococcus, Jeotgalicoccus, and Helicobacter, and a lower abundance of Bifidobacterium. Notably, a strong association between Jeotgalicoccus as well as Staphylococcus and serum 5-HT levels was observed in co-occurrence network. Furthermore, mice that received fecal microbiota transplants from TGR5[-/-] mice displayed anxiety and depression -like behaviors, accompanied by alterations in 5-HT levels in the hippocampus and serum.

LIMITATIONS: Study limitations for gut bacteria were analyzed at the genus level only.

CONCLUSION: TGR5 deletion in mice induces anxiety and depression-like behaviors, linked to reduced 5-HT levels in serum and the hippocampus. Gut microbiota changes play a direct role in these behaviors and serotonin alterations. This implicates TGR5 and gut bacteria in mood regulation, with potential therapeutic implications.}, } @article {pmid37834066, year = {2023}, author = {Zhou, Y and Bi, Z and Hamilton, MJ and Zhang, L and Su, R and Sadowsky, MJ and Roy, S and Khoruts, A and Chen, C}, title = {p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834066}, issn = {1422-0067}, support = {R21AI091907//National Institute of Health/ ; R01DA043252//National Institute of Health/ ; MIN-18-125//National Institute of Food and Agriculture/ ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.}, } @article {pmid37834010, year = {2023}, author = {Jamshidi, P and Farsi, Y and Nariman, Z and Hatamnejad, MR and Mohammadzadeh, B and Akbarialiabad, H and Nasiri, MJ and Sechi, LA}, title = {Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834010}, issn = {1422-0067}, abstract = {Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.}, } @article {pmid37833682, year = {2023}, author = {Diwan, B and Yadav, R and Singh, A and Kumar, D and Sharma, R}, title = {Murine sterile fecal filtrate is a potent pharmacological agent that exerts age-independent immunomodulatory effects in RAW264.7 macrophages.}, journal = {BMC complementary medicine and therapies}, volume = {23}, number = {1}, pages = {362}, pmid = {37833682}, issn = {2662-7671}, support = {IFA17-LSPA79//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, abstract = {BACKGROUND: Sterile fecal filtrate (SFF) is being considered a safer alternative to fecal microbiota transplantation (FMT) therapy; however, its bioactive potency is very little understood. The present study thus assessed the age-dependent immunostimulatory and immunomodulatory attributes of murine SFF in vitro.

METHODS: SFF from young (Y-SFF) and old (O-SFF) Swiss albino mice were prepared. Immunostimulatory and immunomodulatory effects of SFF were evaluated in resting and lipopolysaccharide (LPS) stimulated macrophage cells by measuring intracellular reactive oxygen species (ROS), nitric oxide (NO) production, inflammatory cytokines profile, as well as gene expression of oxidative and inflammatory transcription factors. SFF were also evaluated for native antioxidant capacity by measuring DPPH and ABTS free radical scavenging activity. Bioactive components present in SFF were also determined by GC/MS analysis.

RESULTS: Both Y-SFF and O-SFF induced potent immunostimulatory effects characterized by changes in cell morphology, a significant increase in NO production, ROS levels, and an increased ratio of pro-inflammatory (IL-6, TNF-α, IL-1β) to anti-inflammatory (IL-10) secretory proteins although no significant aggravation in the transcription of NF-κB and Nrf-2 could be observed. Application of LPS to cells significantly augmented a pro-oxidative and pro-inflammatory response which was much higher in comparison to Y-SFF or O-SFF application alone and mediated by strong suppression of Nrf-2 gene expression. Pre-treatment of macrophages with both Y-SFF and O-SFF robustly attenuated cellular hyperresponsiveness to LPS characterized by significantly decreased levels of NO, ROS, and inflammatory cytokines while a concomitant increase in anti-inflammatory protein (IL-10) was observed. Further, both Y-SFF and O-SFF strongly resisted LPS-induced downregulation of Nrf-2 expression although O-SFF appeared to protect cells slightly better from the overall LPS threat. Neat SFF samples exhibited moderate antioxidant capacity and GC/MS analysis of SFF revealed diverse volatile organic compounds characterized by alkanes, organosulphur compounds, furans, amides, amino acids, and antimicrobial elements.

CONCLUSION: Our results indicate that SFF is a potent stimulant of macrophages and confers strong anti-inflammatory effects regardless of donor age thereby suggesting its therapeutic efficacy in lieu of FMT therapy.}, } @article {pmid37831533, year = {2023}, author = {Keller, JJ and Terveer, EM}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {946-947}, doi = {10.1111/apt.17694}, pmid = {37831533}, issn = {1365-2036}, } @article {pmid37831529, year = {2023}, author = {Lesmana, E and Grover, M}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success?.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {950-951}, doi = {10.1111/apt.17724}, pmid = {37831529}, issn = {1365-2036}, } @article {pmid37831526, year = {2023}, author = {Su, Q and Yau, YK and Ng, SC}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success? Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {952-953}, doi = {10.1111/apt.17729}, pmid = {37831526}, issn = {1365-2036}, support = {//InnoHK/ ; //Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; }, } @article {pmid37831525, year = {2023}, author = {Baunwall, SMD and Hansen, MM and Andreasen, SE and Eriksen, MK and Rågård, N and Kelsen, J and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {948-949}, doi = {10.1111/apt.17721}, pmid = {37831525}, issn = {1365-2036}, support = {8056-00006B//Innovationsfonden/ ; R373-2021-1202//Lundbeck Foundation/ ; NNF22OC0074080//Novo Nordisk Fonden/ ; }, } @article {pmid37830929, year = {2023}, author = {Qian, X and Jiang, H and Wu, Y and Shao, H and He, W and He, Y and Bao, X and He, L and Jia, Y and Xu, Z}, title = {Fecal microbiota transplantation combined with prebiotics ameliorates ulcerative colitis in mice.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {}, doi = {10.2217/fmb-2023-0001}, pmid = {37830929}, issn = {1746-0921}, abstract = {Aim: To investigate the effect of treatment with fecal microbiota transplantation (FMT) and galacto- and fructo-oligosaccharides on ulcerative colitis (UC) in mice. Materials & methods: A total of 90 mice, divided into nine groups, were administered FMT or prebiotics or combined treatment. The disease activity index scores, gut microbiota and inflammation factors were evaluated. Results: The treatment using FMT combined with galacto- and fructo-oligosaccharides in a 9:1 ratio significantly reduced intestinal barrier damage and alleviated symptoms of UC. Lactobacillus and Bifidobacterium and short-chain fatty acids were significantly increased after the combined treatment. Conclusion: The results demonstrate that FMT with prebiotics is a new method for UC treatment.}, } @article {pmid37828613, year = {2023}, author = {Guo, C and Kong, L and Xiao, L and Liu, K and Cui, H and Xin, Q and Gu, X and Jiang, C and Wu, J}, title = {The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.}, journal = {Cell & bioscience}, volume = {13}, number = {1}, pages = {188}, pmid = {37828613}, issn = {2045-3701}, support = {82272819//National Natural Science Foundation of China/ ; 81972888//National Natural Science Foundation of China/ ; JNL202204A//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL202219B//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL-2023017D//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; BE2022840//the Primary Research & Development Plan of Jiangsu Province/ ; SYS202202//Shandong Provincial Laboratory Project/ ; 2020YLXK007//the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine/ ; }, abstract = {Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In the last few decades, with the development of next-generation sequencing (NGS) techniques and in-depth research, the view that the gut microbiota intervenes in antitumor immunotherapy through the immune system has been gradually confirmed. Here, we review important studies published in recent years focusing on the influences of microbiota on immune system and the progression of malignancy. Furthermore, we discuss the mechanism by which microbiota affect tumor immunotherapy, including immune checkpoint blockade (ICB) and adoptive T-cell therapy (ACT), and strategies for modulating the microbial composition to facilitate the antitumor immune response. Finally, opportunity and some challenges are mentioned to enable a more systematic understanding of tumor treatment in the future and promote basic research and clinical application in related fields.}, } @article {pmid37824034, year = {2023}, author = {Zhou, J and Qiu, X and Chen, X and Ma, S and Chen, Z and Wang, R and Tian, Y and Jiang, Y and Fan, L and Wang, J}, title = {Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {37824034}, issn = {1976-3794}, support = {WJ2023M169//Scientific research Project of Hubei Provincial Health Commission/ ; No. 22Y26//Scientific and Technological Project of Shiyan City of Hubei Province/ ; S202110929010//National Undergraduate Training Program for Innovation and Entrepreneurship/ ; 2016QDJZR17//Cultivating Project for Young Scholar at Hubei University of Medicine/ ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.}, } @article {pmid37823985, year = {2023}, author = {Jothimani, D and Paramasivam, R and Manoharan, M and Ramachandran, H and Muthusamy, S and Simon, E and Ravichandran, J and Rela, M}, title = {Fecal calprotectin in patients with liver cirrhosis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {37823985}, issn = {0975-0711}, abstract = {BACKGROUND AND OBJECTIVES: Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis.

METHODS: A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48 hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population.

RESULTS: The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: - 53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200 µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) μg/g,p = 0.005.

CONCLUSIONS: FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200 µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.}, } @article {pmid37823635, year = {2023}, author = {Li, J and Zhang, Q and Li, X and Liu, J and Wang, F and Zhang, W and Liu, X and Li, T and Wang, S and Wang, Y and Zhang, X and Meng, Y and Ma, Y and Wang, H}, title = {QingXiaoWuWei decoction alleviates methicillin-resistant Staphylococcus aureus-induced pneumonia in mice by regulating metabolic remodeling and macrophage gene expression network via the microbiota-short-chain fatty acids axis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0034423}, doi = {10.1128/spectrum.00344-23}, pmid = {37823635}, issn = {2165-0497}, abstract = {QingXiaoWuWei decoction (QXWWD) exerts a prominent therapeutic effect on the methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia model in mice; however, its pharmacological mechanisms remain unclear. This study aimed to investigate the underlying pharmacological mechanisms of QXWWD in MRSA-induced pneumonia. In the present study, 62 compounds were identified using high-resolution mass spectrometry. Network analysis, leveraging mass spectrometry, pinpointed the infection-linked, immunity-associated, and inflammation-related pathways as predominant targets. QXWWD significantly alleviated MRSA-induced pneumonia in mice and decreased the levels of pro-inflammatory cytokines and chemokines. 16S ribosomal RNA (16S rRNA) sequencing revealed that QXWWD regulated gut microbiota composition in mice with MRSA-induced pneumonia, which correlated with the enrichment of certain short-chain fatty acids (SCFAs)-producing strains. Further analysis with targeted metabolomics confirmed that the acetic, propionic, and butyric acid levels in the mice's serum were elevated significantly after QXWWD treatment. The fecal microbiota transplantation experiment suggested that gut microbiota from QXWWD-treated mice and SCFAs treatment may alleviate MRSA-induced pneumonia. Additionally, the untargeted metabolomic analysis further demonstrated that metabolic remodeling is significantly regulated by the QXWWD, particularly by the enhancement of the citrate cycle. In the case of QXWWD treatment, global transcriptome profiling revealed that genes, such as NLRP12 and CYP1A1, associated with macrophage antibacterial and immune activity, were downregulated. The results revealed that QXWWD regulated metabolic remodeling and macrophage gene expression network via the microbiota-SCFAs axis and thus alleviated MRSA-induced pneumonia in mice.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.}, } @article {pmid37823111, year = {2023}, author = {He, G and Chen, T and Huang, L and Zhang, Y and Feng, Y and Liu, Q and Yin, X and Qu, S and Yang, C and Wan, J and Liang, L and Yan, J and Liu, W}, title = {Tibetan tea reduces obesity brought on by a high-fat diet and modulates gut flora in mice.}, journal = {Food science & nutrition}, volume = {11}, number = {10}, pages = {6582-6595}, pmid = {37823111}, issn = {2048-7177}, abstract = {It has been shown that Tibetan tea (TT) inhibits obesity and controls lipid metabolism. The fundamental processes by which TT prevents obesity are yet entirely unknown. Consequently, this research aimed to ascertain if TT may prevent obesity by modifying the gut flora. Our research demonstrated that TT prevented mice from gaining weight and accumulating fat due to the high-fat diet (HFD), decreased levels of blood total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and raised levels of high-density lipoprotein cholesterol (HDL-C). Adipogenesis-related genes such as acetyl-Coenzyme A carboxylase 1 (ACC1, LOC107476), fatty acid synthase (Fas, LOC14104), sterol regulatory element-binding protein-1c (SREBP-1c, LOC20787), CCAAT/enhancer-binding protein α (C/EBPα, LOC12606), stearoyl-CoA desaturase 1 (SCD1, LOC20249), and peroxisome proliferator-activated receptor γ (PPARγ, LOC19016) had their expression downregulated by lowering the Firmicutes/Bacteroidetes (F/B) ratio and controlling the number of certain gut bacteria. TT also alleviated HFD-induced abnormalities of the gut microbiota. The Muribaculaceae, Lachnospiraceae NK4A136_group, Alistipes, and Odoribacter families were identified as the major beneficial gut microorganisms using Spearman's correlation analysis. Fecal microbiota transplantation (FMT) demonstrated that TT's anti-obesity and gut microbiota-modulating benefits might be transmitted to mice on an HFD, demonstrating that one of TT's targets for preventing obesity is the gut microbiota. TT also increased the amount of short-chain fatty acids (SCFAs) in the feces, including acetic, propionic, and butyric acids. These results indicate the possible development of TT as a prebiotic to combat obesity and associated disorders. These results suggest that TT may act as a prebiotic against obesity and its associated diseases.}, } @article {pmid37822750, year = {2023}, author = {Zhu, J and Lyu, J and Zhao, R and Liu, G and Wang, S}, title = {Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1272479}, pmid = {37822750}, issn = {1664-302X}, abstract = {Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.}, } @article {pmid37822139, year = {2023}, author = {Tie, Y and Huang, Y and Chen, R and Li, L and Chen, M and Zhang, S}, title = {Current insights on the roles of gut microbiota in inflammatory bowel disease-associated extra-intestinal manifestations: pathophysiology and therapeutic targets.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2265028}, doi = {10.1080/19490976.2023.2265028}, pmid = {37822139}, issn = {1949-0984}, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal tract. In addition to digestive symptoms, patients with IBD may also develop extra-intestinal manifestations (EIMs), the etiology of which remains undefined. The gut microbiota has been reported to exert a critical role in the pathogenesis of IBD, with a similar pattern of gut dysbiosis observed between patients with IBD and those with EIMs. Therefore, it is hypothesized that the gut microbiota is also involved in the pathogenesis of EIMs. The potential mechanisms are presented in this review, including: 1) impaired gut barrier: dysbiosis induces pore formation in the intestinal epithelium, and activates pattern recognition receptors to promote local inflammation; 2) microbial translocation: intestinal pathogens, antigens, and toxins translocate via the impaired gut barrier into extra-intestinal sites; 3) molecular mimicry: certain microbial antigens share similar epitopes with self-antigens, inducing inflammatory responses targeting extra-intestinal tissues; 4) microbiota-related metabolites: dysbiosis results in the dysregulation of microbiota-related metabolites, which could modulate the differentiation of lymphocytes and cytokine production; 5) immunocytes and cytokines: immunocytes are over-activated and pro-inflammatory cytokines are excessively released. Additionally, we summarize microbiota-related therapies, including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation, to promote better clinical management of IBD-associated EIMs.}, } @article {pmid37821652, year = {2023}, author = {Yost, RT and Fowler, AE and Adler, LS}, title = {Gut Transplants from Bees Fed an Antipathogenic Pollen Diet Do Not Confer Pathogen Resistance to Recipients.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, pmid = {37821652}, issn = {1432-184X}, support = {2128221//National Science Foundation/ ; NE2001//U.S. Department of Agriculture/ ; }, abstract = {Pollinators are threatened by diverse stressors, including microbial pathogens such as Crithidia bombi. Consuming sunflower pollen dramatically reduces C. bombi infection in the bumble bee Bombus impatiens, but the mechanism behind this medicinal effect is unclear. We asked whether diet mediates resistance to C. bombi through changes in the gut microbiome. We hypothesized that sunflower pollen changes the gut microbiome, which in turn reduces Crithidia infection. To test this, we performed a gut transplant experiment. We fed donor bees either a sunflower pollen treatment or buckwheat pollen as a control treatment and then inoculated recipient bees with homogenized guts from either sunflower-fed or buckwheat-fed donor bees. All recipient bees were then fed a wildflower pollen diet. Two days after the transplant, we infected recipients with C. bombi, and 2 days later, we provided another donor gut transplant. To quantify infection, we performed both fecal screens and dissections of the recipient bees. We found no significant differences in C. bombi infection intensity or presence between bees that received sunflower-fed microbiomes versus buckwheat-fed microbiomes. This suggests that sunflower pollen's effects on pathogen resistance are not mediated by gut microbiota.}, } @article {pmid37820424, year = {2023}, author = {Xu, C and Zhao, L and Zhou, W and Li, Y and Hu, H and Wang, Z}, title = {Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.}, journal = {International immunopharmacology}, volume = {124}, number = {Pt B}, pages = {111009}, doi = {10.1016/j.intimp.2023.111009}, pmid = {37820424}, issn = {1878-1705}, abstract = {Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.}, } @article {pmid37820064, year = {2023}, author = {Liu, Y and Tu, J and Shi, L and Fang, Z and Fan, M and Zhang, J and Ding, L and Chen, Y and Wang, Y and Zhang, E and Xu, S and Sharma, N and Gillece, JD and Reining, LJ and Jin, L and Huang, W}, title = {CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000627}, pmid = {37820064}, issn = {1527-3350}, abstract = {BACKGROUND AIMS: Although the benefits of vertical sleeve gastrectomy surgery (VSG) are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine a role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG.

APPROACH RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout (KO), we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, shRNA mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation (FMT) from wild type (WT)-VSG mice (vs. FMT from WT-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received FMT from KO-sham and KO-VSG mice.

CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and GM profile by targeting CYP8B1 may provide novel insight into the development of therapies that non-invasively mimic bariatric surgery to treat obesity and its complications.}, } @article {pmid37819130, year = {2023}, author = {Van Den Ham, KM and Little, MR and Bednarski, OJ and Fusco, EM and Mandal, RK and Mitra, R and Li, S and Doumbo, S and Doumtabe, D and Kayentao, K and Ongoiba, A and Traore, B and Crompton, PD and Schmidt, NW}, title = {Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0155423}, doi = {10.1128/spectrum.01554-23}, pmid = {37819130}, issn = {2165-0497}, abstract = {Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. IMPORTANCE There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.}, } @article {pmid37818040, year = {2023}, author = {Zhan, X and Zuo, Q and Huang, G and Qi, Z and Wang, Y and Zhu, S and Zhong, Y and Xiong, Y and Chen, T and Tan, B}, title = {Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1236272}, pmid = {37818040}, issn = {2235-2988}, abstract = {Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.}, } @article {pmid37815701, year = {2023}, author = {Emile, SH and Horesh, N and Freund, MR and Garoufalia, Z and Gefen, R and Khan, SM and Silva-Alvarenga, E and Wexner, SD}, title = {A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {}, pmid = {37815701}, issn = {1873-4626}, abstract = {BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).

METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.

RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I[2] = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I[2] = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.

CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.}, } @article {pmid37814565, year = {2023}, author = {Korpak, K and Defourny, L and Lali, S and Delvallée, M and Demeester, R and Toussaint, E}, title = {Treatment of recurrent Clostridioides difficile infections with faecal microbiota transplantation: peri-procedural methods in a consecutive case series.}, journal = {Acta gastro-enterologica Belgica}, volume = {86}, number = {3}, pages = {486-489}, doi = {10.51821/86.3.11795}, pmid = {37814565}, issn = {1784-3227}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has high efficacy against recurrent Clostridioides difficile infection (CDI). Despite the increasing use of this therapy, the delay between diagnosis and treatment is excessive. Furthermore, donor selection is an important and time-consuming process.

METHODS: We reviewed patients who underwent FMT for recurrent CDI at the CHU Charleroi Hospital between 2015 and 2022. The general context, type of administration, adverse events, and donor selection were reported. FMT was conducted using gastroduodenoscopy, colonoscopy, and enema with either fresh or frozen material.

RESULTS: Ten patients with multiple comorbidities were treated by FMT. Seven patients were cured after one procedure. One patient was successfully cured after a change to an unrelated donor, and preliminary efficacy was established.

CONCLUSIONS: FMT is an effective treatment that should be considered during the earlier phases of treatment. Stool donors should be thoroughly screened for infectious diseases and other criteria related to microbiota composition.}, } @article {pmid37814439, year = {2023}, author = {Zhang, J and Zhang, C and Zhang, T and Zhang, L and Duan, L}, title = {Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.}, journal = {Journal of neurogastroenterology and motility}, volume = {29}, number = {4}, pages = {520-531}, doi = {10.5056/jnm22182}, pmid = {37814439}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients.

METHODS: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days' colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation.

RESULTS: Visceral hypersensitivity induced by IBS-fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations.

CONCLUSIONS: Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.}, } @article {pmid37813835, year = {2023}, author = {Han, D and Wu, Y and Lu, D and Pang, J and Hu, J and Zhang, X and Wang, Z and Zhang, G and Wang, J}, title = {Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation.}, journal = {Cell death & disease}, volume = {14}, number = {10}, pages = {656}, pmid = {37813835}, issn = {2041-4889}, support = {32125036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32172750//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31902170//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Polyphenols/pharmacology/metabolism ; Neutrophils/metabolism ; Ellagic Acid/metabolism/pharmacology ; *Colitis/metabolism ; Inflammation/pathology ; Diet ; Macrophages/metabolism ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/pathology ; }, abstract = {Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.}, } @article {pmid37809261, year = {2023}, author = {Masood, L and Müller, A and Ali, NZ and Mummadisetty, A and Yahya, A and Burugu, SS and Sajid, R and Lakkimsetti, M and Sagireddy, S and Abdin, ZU and Nazir, Z}, title = {A Narrative Literature Review on Sepsis: A Primary Manifestation of Colorectal Neoplasm.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44803}, pmid = {37809261}, issn = {2168-8184}, abstract = {Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.}, } @article {pmid37807005, year = {2023}, author = {Arjomand Fard, N and Bording-Jorgensen, M and Wine, E}, title = {A Potential Role for Gut Microbes in Mediating Effects of Omega-3 Fatty Acids in Inflammatory Bowel Diseases: A Comprehensive Review.}, journal = {Current microbiology}, volume = {80}, number = {11}, pages = {363}, pmid = {37807005}, issn = {1432-0991}, abstract = {Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.}, } @article {pmid37806386, year = {2023}, author = {Kumbhare, SV and Pedroso, I and Ugalde, JA and Márquez-Miranda, V and Sinha, R and Almonacid, DE}, title = {Drug and gut microbe relationships: Moving beyond antibiotics.}, journal = {Drug discovery today}, volume = {}, number = {}, pages = {103797}, doi = {10.1016/j.drudis.2023.103797}, pmid = {37806386}, issn = {1878-5832}, abstract = {Our understanding of drug-microbe relationships has evolved from viewing microbes as mere drug producers to a dynamic, modifiable system where they can serve as drugs or targets of precision pharmacology. This review highlights recent findings on the gut microbiome, particularly focusing on four aspects of research: (i) drugs for bugs, covering recent strategies for targeting gut pathogens; (ii) bugs as drugs, including probiotics; (iii) drugs from bugs, including postbiotics; and (iv) bugs and drugs, discussing additional types of drug-microbe interactions. This review provides a perspective on future translational research, including efficient companion diagnostics in pharmaceutical interventions. Teaser This review highlights the dynamic relationship between drugs and bugs in the human gut microbiome, providing insights into potential strategies for novel therapies and companion diagnostics for precision pharmacology.}, } @article {pmid37806074, year = {2023}, author = {Pötgens, SA and Lecop, S and Havelange, V and Li, F and Neyrinck, AM and Neveux, N and Maertens, J and Walter, J and Schoemans, H and Delzenne, NM and Bindels, LB}, title = {Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {42}, number = {11}, pages = {2214-2228}, doi = {10.1016/j.clnu.2023.09.021}, pmid = {37806074}, issn = {1532-1983}, abstract = {BACKGROUND & AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.

METHODS: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.

RESULTS: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.

CONCLUSION: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.

TRIAL REGISTRATION: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.}, } @article {pmid37805634, year = {2023}, author = {Peña-Cearra, A and Song, D and Castelo, J and Palacios, A and Lavín, JL and Azkargorta, M and Elortza, F and Fuertes, M and Pascual-Itoiz, MA and Barriales, D and Martín-Ruiz, I and Fullaondo, A and Aransay, AM and Rodríguez, H and Palm, NW and Anguita, J and Abecia, L}, title = {Mitochondrial dysfunction promotes microbial composition that negatively impacts on ulcerative colitis development and progression.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {74}, pmid = {37805634}, issn = {2055-5008}, support = {PID2021-124328OB-100//Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)/ ; }, abstract = {Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ[-/-] associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.}, } @article {pmid37802720, year = {2023}, author = {Portincasa, P and Khalil, M and Graziani, A and Frühbeck, G and Baffy, G and Garruti, G and Di Ciaula, A and Bonfrate, L}, title = {Gut microbes in metabolic disturbances. Promising role for therapeutic manipulations?.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2023.10.002}, pmid = {37802720}, issn = {1879-0828}, abstract = {The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.}, } @article {pmid37802272, year = {2023}, author = {Jangi, S and Hsia, K and Zhao, N and Kumamoto, CA and Friedman, S and Singh, S and Michaud, DS}, title = {Dynamics of the Gut Mycobiome in Patients with Ulcerative Colitis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2023.09.023}, pmid = {37802272}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC), however it remains unclear if fungal composition is altered during active vs quiescent disease.

METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n=52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity vs remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data.

RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (p-adj < 1 x 10[-4]) compared to during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (p<0.05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii and Bacteroides dorei relative abundance (p<0.05) during remission, however these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (AUC ∼0.80), with Candida relative abundance critical to the success of the model.

CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.}, } @article {pmid37800288, year = {2023}, author = {Hosonuma, M and Murayama, M and Yoshimura, K}, title = {[The Gut Microbiota Metabolite A Enhances the Anti-Tumor Effects of Anti-PD-1 Antibody Therapy through Immune Modulation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {9}, pages = {960-964}, pmid = {37800288}, issn = {0385-0684}, abstract = {The gut microbiota is an important partner in humans, and its dysregulation is associated with the development of inflammatory bowel diseases and cancer. Furthermore, the gut microbiota is involved in the therapeutic effects of immune checkpoint inhibitors, and controlling the gut microbiota may enhance the efficacy of cancer immunotherapy. Currently, the development of therapies to control the gut microbiota includes fecal transplantation, probiotics, prebiotics, and postbiotics. In this article, we introduce SCFA-A, a type of short-chain fatty acid(SCFA)and a metabolite of gut microbiota, which is involved in the activation of T cells and induction of M1 macrophages, thereby enhancing the anti-tumor effects of anti- PD-1 antibody therapy. SCFA-A holds promise as a novel treatment approach in cancer immunotherapy as a postbiotic.}, } @article {pmid37798771, year = {2023}, author = {Zhou, C and Li, J and Guo, C and Zhou, Z and Yang, Z and Zhang, Y and Jiang, J and Cai, Y and Zhou, J and Xia, M and Ming, Y}, title = {Alterations in gut microbiome and metabolite profile of patients with Schistosoma japonicum infection.}, journal = {Parasites & vectors}, volume = {16}, number = {1}, pages = {346}, pmid = {37798771}, issn = {1756-3305}, support = {81771722//National Natural Science Foundation of China/ ; 2021SK2032//Key Research and Development Plan of Hunan Province/ ; }, abstract = {BACKGROUND: Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection.

METHODS: This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis.

RESULTS: The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum.

CONCLUSIONS: This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.}, } @article {pmid37798034, year = {2023}, author = {Vendrik, KE and Chernova, VO and Kuijper, EJ and Terveer, EM and van Hilten, JJ and Contarino, MF and , }, title = {Safety and feasibility of faecal microbiota transplantation for patients with Parkinson's disease: a protocol for a self-controlled interventional donor-FMT pilot study.}, journal = {BMJ open}, volume = {13}, number = {10}, pages = {e071766}, doi = {10.1136/bmjopen-2023-071766}, pmid = {37798034}, issn = {2044-6055}, abstract = {INTRODUCTION: Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.

METHODS AND ANALYSIS: We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.

ETHICS AND DISSEMINATION: This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.

TRIAL REGISTRATION NUMBER: International Clinical Trial Registry Platform: NL9438.}, } @article {pmid37797200, year = {2023}, author = {Han, Q and Liu, R and Wang, H and Zhang, R and Liu, H and Li, J and Bao, J}, title = {Gut Microbiota-Derived 5-Hydroxyindoleacetic Acid Alleviates Diarrhea in Piglets via the Aryl Hydrocarbon Receptor Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c04658}, pmid = {37797200}, issn = {1520-5118}, abstract = {With the improvement in sow prolificacy, formula feeding has been increasingly used in the pig industry. Diarrhea remains a serious health concern in formula-fed (FF) piglets. Fecal microbiota transplantation (FMT) is an efficacious strategy to reshape gut microbiota and the metabolic profile for treating diarrhea. This study aims to investigate whether FMT from breast-fed piglets could alleviate diarrhea in FF piglets. The piglets were randomly assigned to the control (CON) group, FF group, and FMT group. Our results showed that FF piglets exhibited a higher diarrhea incidence, damaged colonic morphology, and disrupted barrier function. In contrast, FMT treatment normalized the morphology and barrier function. FMT suppressed the JNK/MAPK pathway and production of proinflammatory cytokines. Additionally, FF piglets had a lower abundance of the beneficial bacterial genus Bifidobacterium compared to CON piglets. Following FMT administration, Bifidobacterium was restored. Meanwhile, 5-HIAA, a metabolite of tryptophan, and AHR-responsive CYP1A1 and CYP1B1 were upregulated. Importantly, integrated multiomics analysis revealed a strong positive correlation between Bifidobacterium and 5-HIAA. In vitro, 5-HIAA supplementation reversed the LPS-induced disruption of tight junctions and production of proinflammatory cytokines in IPEC-J2 cells. In conclusion, FMT reduced diarrhea incidence and improved growth performance. The alleviative effect of FMT on diarrhea was associated with Bifidobacterium and 5-HIAA.}, } @article {pmid37796494, year = {2023}, author = {Stewart, AK and Foley, MH and Dougherty, MK and McGill, SK and Gulati, AS and Gentry, EC and Hagey, LR and Dorrestein, PC and Theriot, CM and Dodds, JN and Baker, ES}, title = {Using Multidimensional Separations to Distinguish Isomeric Amino Acid-Bile Acid Conjugates and Assess Their Presence and Perturbations in Model Systems.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.3c03057}, pmid = {37796494}, issn = {1520-6882}, abstract = {Bile acids play key roles in nutrient uptake, inflammation, signaling, and microbiome composition. While previous bile acid analyses have primarily focused on profiling 5 canonical primary and secondary bile acids and their glycine and taurine amino acid-bile acid (AA-BA) conjugates, recent studies suggest that many other microbial conjugated bile acids (or MCBAs) exist. MCBAs are produced by the gut microbiota and serve as biomarkers, providing information about early disease onset and gut health. Here we analyzed 8 core bile acids synthetically conjugated with 22 proteinogenic and nonproteogenic amino acids totaling 176 MCBAs. Since many of the conjugates were isomeric and only 42 different m/z values resulted from the 176 MCBAs, a platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) was used for their separation. Their molecular characteristics were then used to create an in-house extended bile acid library for a combined total of 182 unique compounds. Additionally, ∼250 rare bile acid extracts were also assessed to provide additional resources for bile acid profiling and identification. This library was then applied to healthy mice dosed with antibiotics and humans having fecal microbiota transplantation (FMT) to assess the MCBA presence and changes in the gut before and after each perturbation.}, } @article {pmid37796016, year = {2023}, author = {Kamer, O and Rinott, E and Tsaban, G and Kaplan, A and Yaskolka Meir, A and Zelicha, H and Knights, D and Tuohy, K and Fava, F and Uwe Scholz, M and Ziv, O and Rubin, E and Blüher, M and Stumvoll, M and Ceglarek, U and Clément, K and Koren, O and Hu, FB and Stampfer, MJ and Wang, DD and Youngster, I and Shai, I}, title = {Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2264457}, doi = {10.1080/19490976.2023.2264457}, pmid = {37796016}, issn = {1949-0984}, abstract = {We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.}, } @article {pmid37795613, year = {2023}, author = {Wang, C and Liu, XL and Sun, Q and Zhao, FY and Dai, PQ and Li, LX and Hu, DG}, title = {Apple consumption affects cecal health by regulating 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) levels through modifying the microbiota in rats.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo03207h}, pmid = {37795613}, issn = {2042-650X}, abstract = {Apples are rich in many nutrients and functional components. However, the mechanism of the effect of fresh apple consumption on rats remains unclear. In the present study, fresh apples (10 g kg[-1]) were added to the diet of Wistar rats, and changes in the microbiota and metabolite content of the cecum were analyzed after 28 days of feeding, and changes in the 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) content and indicators related to inflammation, oxidative stress, and apoptosis were detected. Subsequently, a fecal microbiota transplantation (FMT) protocol was designed and carried out to verify the relationship between the microbiota and 12(S)-HETE, the cecal structure, and inflammatory factors. The results show that apple consumption significantly reduced the serum levels of alanine aminotransferase (ALT) and immunoglobulin G (IgG), altered the cecal histomorphology, and significantly upregulated the gene expression of claudin-1 and zonula occludens-1 (ZO-1), which encode tight junction proteins. Apple consumption also changed the structure of the cecal microbiota, increasing the abundance of some species (such as Shuttleworthia) and decreasing the abundance of others (such as Alphaproteobacteria). Metabolomic screening identified 64 significantly different metabolites. The FMT results showed that apple consumption reduced 12(S)-HETE metabolite levels in the cecal contents, improved the intestinal structure, and reduced the levels of proinflammatory factor expression by altering the cecal microbiota. In conclusion, this study provides further insight into the effects of apples on animals using rats as experimental animals. It provides basic data for future exploration of the mechanisms of the effect of apple consumption on humans.}, } @article {pmid37795305, year = {2023}, author = {Yang, Y and Cui, B and Lv, Y and Lu, X and Shen, W and Feng, M and Ding, X and Dong, P and Wang, Y}, title = {Plateau pika fecal microbiota transplantation ameliorates inflammatory bowel disease manifestations in a mouse model of colitis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1228778}, pmid = {37795305}, issn = {1664-302X}, abstract = {Inflammatory bowel disease (IBD) is a serious global public health concern. Although the pathogenesis of the disease is currently unknown, it has been reported to be associated with both intestinal microbiota and inflammatory mediators. There is evidence suggesting that the feces of the Plateau pika is useful for treating gastrointestinal injuries and pain. Although fecal microbiota transplantation is highly efficacious intervention for IBD prevention, however, potential the transfer of pathogenic microbes or toxic substances is potentially hazardous. Fortunately, micropore filtering of the donor feces can minimize the risk of bacterial infection allowing retention of the therapeutic effects of the residual bacteriophages. Here, we demonstrated that Plateau pika feces not only alleviated the IBD symptoms but also promoted optimal structure and composition of the intestinal microbiota. Additionally, Plateau pika feces transfer also enhanced phenotypic features, such as, body-weight, disease activity index, and histological scores. In conclusion, Plateau pika feces was found to protect mice against colitis induced by dextran sodium sulfate by reducing inflammation and regulating microbial dysbiosis. These findings suggest the potential of Plateau pika feces as an alternative therapy for IBD.}, } @article {pmid37794047, year = {2023}, author = {Li, G and Liu, L and Lu, T and Sui, Y and Zhang, C and Wang, Y and Zhang, T and Xie, Y and Xiao, P and Zhao, Z and Cheng, C and Hu, J and Chen, H and Xue, D and Chen, H and Wang, G and Kong, R and Tan, H and Bai, X and Li, Z and McAllister, F and Li, L and Sun, B}, title = {Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {6179}, pmid = {37794047}, issn = {2041-1723}, support = {82270665//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82070658//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.}, } @article {pmid37793354, year = {2023}, author = {Shi, X and Li, Z and Lin, W and Shi, W and Hu, R and Chen, G and Li, X and Li, X and Zhang, S}, title = {Altered intestinal microbial flora and metabolism in patients with idiopathic membranous nephropathy.}, journal = {American journal of nephrology}, volume = {}, number = {}, pages = {}, doi = {10.1159/000533537}, pmid = {37793354}, issn = {1421-9670}, abstract = {INTRODUCTION: Dysbiosis of the intestinal microbiome and related metabolites have been observed in chronic kidney disease (CKD), yet their roles in idiopathic membranous nephropathy (IMN) is poorly understood.

METHODS: In this study, we describe the variation of intestinal bacteria and fecal metabolites in patients with IMN in Chinese population. Stool samples are collected from 41 IMN patients at the beginning of diagnosis confirmation and 41 gender and age matched healthy control (HC). Microbial communities are investigated by sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun, and the correlation between intestinal bacteria and IMN clinical characteristics is also analyzed. Untargeted metabolomic analysis is performed to explore the relationship between colon's microbiota and fecal metabolites.

RESULTS: IMN gastrointestinal microbiota demonstrates lower richness and diversity compared to HC, and exhibits a marked taxonomic and inferred functional dysbiosis when compared to HC. Some genera are closely related to the clinical parameters, such as Citrobacter and Akkermansia. 20 characteristic microbial biomarkers are selected to establish a disease prediction model with a diagnostic accuracy of 93.53%. Fecal metabolomics shows that tryptophan metabolism is reduced in IMN patients but uremic toxin accumulation in feces is not noticeable. Fecal microbiota transplantation demonstrates that gut dysbiosis impairs gut permeability in microbiota-depleted mice and induces NOD-like receptor activation in kidneys.

DISCUSSION/CONCLUSIONS: Clarifying the changes in intestinal microbiota in IMN patients will help further know the pathogenesis of this disease, and microbiota-targeted biomarkers will provide a potentially powerful tool for diagnosing and treating IMN.}, } @article {pmid37793163, year = {2023}, author = {Zhang, S and Zhao, X and Wang, X and Jin, H and Chen, L and Ma, Y and Chi, Y and Zhang, J and Zhang, J and Gao, Y}, title = {Gut microecology may be involved in pathogenesis of Hashimoto's thyroiditis by reducing production of hydrogen sulfide.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgad588}, pmid = {37793163}, issn = {1945-7197}, abstract = {CONTEXT: Hashimoto's thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis.

OBJECTIVE: To illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels.

METHODS: We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomized into four groups: experimental autoimmune thyroiditis (EAT) group, EAT + Health group, EAT + HT group, and EAT + HT + H2S group. 16S rRNA sequencing was performed to examine gut microbiota alterations and H2S production pathway. Serum TgAb and H2S levels were assayed by ELISA and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry.

RESULTS: The gut microbiota was different after FMT among the EAT, EAT + Health and EAT + HT groups. The thyroiditis score assessed by H&E staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Th1 and Th17 cell differentiation ratios were increased in EAT + HT group compared to the other three groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Health group.

CONCLUSIONS: H2S alleviated thyroiditis severity and related immune disorders, which was aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.}, } @article {pmid37791342, year = {2023}, author = {Kamiya, S}, title = {Microbial ecology between Clostridioides difficile and gut microbiota.}, journal = {Bioscience of microbiota, food and health}, volume = {42}, number = {4}, pages = {229-235}, pmid = {37791342}, issn = {2186-6953}, abstract = {Clostridioides difficile colonizes a polymicrobial environment in the intestine and is a causative agent for antibiotic-associated diarrhea (AAD) and pseudomembranous colitis (PMC). The most important virulence factors of C. difficile are bacterial toxins, and three toxins (toxin A, toxin B, and binary toxin) are produced by toxigenic strains. Other virulence factors include spores, flagella, capsules, biofilms, hydrolytic enzymes and adhesins. C. difficile infection (CDI) is specifically diagnosed by anaerobic culture and toxin detection by either nucleic acid amplification test (NAAT) or enzyme-linked immunosorbent assay (ELISA). For treatment of CDI, metronidazole, vancomycin and fidaxomicin are used based on the severity of CDI. Mutual interaction between C. difficile and gut microbiota is associated with pathogenesis of CDI, and decreased microbial diversity with altered gut microbiome was detected in CDI patients. Restoration of certain gut microbiota is considered to be potentially effective for the prevention and treatment of CDI, and an ideal goal for CDI patients is restoration of the gut microbiota to a healthy state. Fecal microbiota transplantation (FMT) is a highly successful method of microbiome restoration and has been reported to be effective for the prevention of recurrent CDI. In addition, approaches to restoring the gut microbiota by using probioitcs and live biotherapeutic products (LBPs) are currently being studied to examine the effect on CDI. Further microbial ecological research on C. difficile and gut microbiota could lead to a better understanding of the pathogenesis and treatment of CDI.}, } @article {pmid37789073, year = {2023}, author = {Battipaglia, G and Mooyaart, JE and Meyer, R and Mohty, M and Sadowska-Klasa, A and Goloshchapov, O and Locatelli, F and Styczynski, J and Pavlu, J and Dybko, J and Bronin, G and Salmenniemi, U and Jindra, P and Hoogenboom, JD and Kuball, J and Ruggeri, A and Malard, F}, title = {Current use of fecal microbiota transfer in patients with hematologic diseases: a survey on behalf of the Cellular Therapy and Immunobiology Working Party of the EBMT.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {37789073}, issn = {1476-5365}, } @article {pmid37788279, year = {2023}, author = {Wang, J and Liu, X and Sun, R and Mao, H and Liu, M and Jin, X}, title = {Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2.}, journal = {PLoS pathogens}, volume = {19}, number = {10}, pages = {e1011683}, pmid = {37788279}, issn = {1553-7374}, mesh = {Animals ; Humans ; Mice ; Fibrosis ; RNA, Ribosomal, 16S/genetics ; *Toll-Like Receptor 2/genetics ; *Verrucomicrobia/genetics ; Trichinella spiralis ; *Trichinellosis/immunology ; }, abstract = {Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.}, } @article {pmid37787998, 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 = {Potential of fecal microbiota transplantation to prevent acute graft-versus-host disease: Analysis from a phase 2 trial.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {}, number = {}, pages = {}, doi = {10.1158/1078-0432.CCR-23-2369}, pmid = {37787998}, issn = {1557-3265}, abstract = {PURPOSE: Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute graft-versus-host disease (aGVHD). In our recent randomized phase 2 trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against acute GVHD.

PATIENTS AND METHODS: We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a pre-planned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).

RESULTS: dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%, range 1.6-74.3%) than those who developed grade II-IV aGVHD (median 25.3%, range 2.2-34.8%) (P = 0.006). The cumulative incidence of grade II-IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf (14.3% [95%CI, 2.1-37.5%] vs. 76.9% [95% CI, 39.7-92.8%], P = 0.008). The only determinant of dMf in cross-validated LASSO-regularized regression was the patient's pre-FMT microbiota diversity (Pearson's correlation coefficient -0.82, P = 1.6x10-9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.

CONCLUSIONS: FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.}, } @article {pmid37787835, year = {2023}, author = {Li, S and Zhao, L and Xiao, J and Guo, Y and Fu, R and Zhang, Y and Xu, S}, title = {The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {37787835}, issn = {1573-4919}, support = {No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; }, abstract = {There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.}, } @article {pmid37787395, year = {2023}, author = {Lo Porto, D and Mularoni, A and Castagnola, E and Saffioti, C}, title = {Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14159}, doi = {10.1111/tid.14159}, pmid = {37787395}, issn = {1399-3062}, support = {Ricerca Corrente: RC 2022 Linea 1//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.}, } @article {pmid37787118, year = {2023}, author = {Shou, D and Luo, Q and Tang, W and Cao, C and Huang, H and Chen, H and Zhou, Y}, title = {Hepatobiliary and pancreatic: Multi-donor fecal microbiota transplantation attenuated high-fat diet-induced hepatic steatosis in mice by remodeling the gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16359}, pmid = {37787118}, issn = {1440-1746}, support = {81970507//Natural Science Foundation of China/ ; 82170585//Natural Science Foundation of China/ ; 2023A0505010007//Science and Technology Planning Project of Guangdong Province/ ; 2021A1515011290//Natural Science Foundation of Guangdong Province/ ; 2023A03J0955//Guangzhou Municipal Science and Technology Project/ ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms.

METHODS: Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3 weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12 weeks.

RESULTS: Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1β, IL-6, TNF-α, IFN-γ, and IL-1β mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia.

CONCLUSION: NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.}, } @article {pmid37781523, year = {2023}, author = {Shao, X and Liu, L and Zhou, Y and Zhong, K and Gu, J and Hu, T and Yao, Y and Zhou, C and Chen, W}, title = {High-fat diet promotes colitis-associated tumorigenesis by altering gut microbial butyrate metabolism.}, journal = {International journal of biological sciences}, volume = {19}, number = {15}, pages = {5004-5019}, pmid = {37781523}, issn = {1449-2288}, abstract = {Background: Dietary fat intake is associated with an increased risk of colitis associated cancer (CAC). A high-fat diet (HFD) leads to systemic low-grade inflammation. The colon is believed to be the first organ suffering from inflammation caused by the infiltration of pro-inflammatory macrophages, and promotes CAC progression. We explored the role of HFD in driving CAC by altering gut microbial butyrate metabolism. Methods: Changes in the gut microbiota caused by HFD were investigated via HFD treatment or fecal microbiota transplantation (FMT). The underlying mechanisms were further explored by analyzing the role of gut microbiota, microbial butyrate metabolism, and NLRP3 inflammasome in colon tissues in a CAC mouse model. Results: HFD accelerated CAC progression in mice, and it could be reversed by broad-spectrum antibiotics (ABX). 16S-rRNA sequencing revealed that HFD inhibited the abundance of butyrate-producing bacteria in the gut. The level of short-chain fatty acids (SCFAs), especially butyrate, in the gut of mice treated with HFD was significantly reduced. In addition, treatment with exogenous butyrate reversed the M1 polarization of proinflammatory macrophages, aggravation of intestinal inflammation, and accelerated tumor growth induced by HFD; the NLRP3/Caspase-1 pathway activated by HFD in the colon was also significantly inhibited. In vitro, macrophages were treated with lipopolysaccharide combined with butyrate to detect the M1 polarization level and NLRP3/Caspase-1 pathway expression, and the results were consistent with those of the in vivo experiments. Conclusion: HFD drives colitis-associated tumorigenesis by inducing gut microbial dysbiosis and inhibiting butyrate metabolism to skew macrophage polarization. Exogenous butyrate is a feasible new treatment strategy for CAC, and has good prospect for clinical application.}, } @article {pmid37781044, year = {2023}, author = {Zhang, L and Ji, Q and Chen, Q and Wei, Z and Liu, S and Zhang, L and Zhang, Y and Li, Z and Liu, H and Sui, H}, title = {Akkermansia muciniphila inhibits tryptophan metabolism via the AhR/β-catenin signaling pathway to counter the progression of colorectal cancer.}, journal = {International journal of biological sciences}, volume = {19}, number = {14}, pages = {4393-4410}, pmid = {37781044}, issn = {1449-2288}, mesh = {Humans ; Mice ; Animals ; beta Catenin/metabolism ; Tryptophan/adverse effects ; Receptors, Aryl Hydrocarbon/genetics/metabolism ; Base Composition ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; *Colorectal Neoplasms/metabolism ; *Colonic Neoplasms ; Wnt Signaling Pathway ; Mice, Inbred C57BL ; }, abstract = {Akkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism in CRC development remains inconclusive. In this study, we first confirmed the inhibitory effect of A. muciniphila on CRC formation and analyzed the metabolic role of intestinal flora in human Polyps, A-CRA (advanced colorectal adenoma) and CRC samples. To better clarify the role of A. muciniphila in CRC development, a pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection with or without A. muciniphila. Metabolomic analysis and RNA-seq analysis showed tryptophan-mediated aryl hydrocarbon receptor (AhR) was significantly down-regulated in A. muciniphila-infected CRC mice. Then, mice with intestinal specific AhR deficiency (AhR[fl/fl] Cre) were generated and were used in 2 murine models: AOM/DSS treatment as a model of carcinogen-induced colon cancer and a genetically induced model using Apc[Min/+] mice. Notably, AhR deficiency inhibited CRC growth in the AOM/DSS and Apc[Min/+] mouse model. Moreover, AhR deficiency inhibited, rather than enhanced, tumor formation and tumor-derived organoids in Apc-deficient cells both in vivo and in vitro by activating Wnt/β-catenin signaling and TCF4/LEF1-dependent transcription. Furthermore, the antitumor effectiveness of A. muciniphila was abolished either in a human colon cancer tumor model induced by subcutaneous transplantation of AhR-silenced CRC cells, or AhR-deficienty spontaneous colorectal cancer model. In conclusion, supplementation with A. muciniphila. protected mice from CRC development by specifically inhibiting tryptophan-mediated AhR/β-catenin signaling.}, } @article {pmid37780282, year = {2023}, author = {Li, W and Zhang, W and Fan, X and Xu, H and Yuan, H and Wang, Y and Yang, R and Tian, H and Wu, Y and Yang, H}, title = {Fructo-oligosaccharide enhanced bioavailability of polyglycosylated anthocyanins from red radish via regulating gut microbiota in mice.}, journal = {Food chemistry: X}, volume = {19}, number = {}, pages = {100765}, pmid = {37780282}, issn = {2590-1575}, abstract = {The anthocyanins from red radish (ARR) rich in polyglycosylated pelargonidin glucosides were used as pigment. However, bioavailability of anthocyanins was considered at low level. This work examined the intensive effects of fructo-oligosaccharide (FOS) on ARR bioavailability. Pelargonidin, cyanidin and pelargonidin-3-glucoside showed higher level in serum of mice fed with FOS together with ARR for 8 weeks than that fed with only ARR. Co-ingestion of FOS and ARR more effectively elevated the hepatic antioxidant activity by increase in total antioxidant capacity and activities of superoxide dismutase and glutathione peroxidase when compared with intake of ARR. FOS also markedly increased pelargonidin level in cecum of mice. 16S RNA sequencing found that Bacteroides genus play an important role in FOS elevating bioavailability of ARR. Fecal bacteria transplantation verified the positive effects of FOS on ARR bioavailability. These results suggested that combined ingestion of FOS and ARR is effective strategy for bioactivity of ARR.}, } @article {pmid37779873, year = {2023}, author = {Machado, AP and Shatila, M and De Toni, EN and Török, HP and Philpott, J and Zhao, D and Zhou, Y and Varatharajalu, K and Shafi, MA and Zhang, HC and Thomas, AS and Wang, Y}, title = {Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.}, journal = {Journal of Cancer}, volume = {14}, number = {14}, pages = {2686-2693}, pmid = {37779873}, issn = {1837-9664}, abstract = {Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.}, } @article {pmid37778924, year = {2023}, author = {Custer, GF and Bresciani, L and Dini-Andreote, F}, title = {Toward an integrative framework for microbial community coalescence.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2023.09.001}, pmid = {37778924}, issn = {1878-4380}, abstract = {Community coalescence is defined as the mixing of intact ecological communities. From river confluences to fecal microbiota transplantation, community coalescence constitutes a common ecological occurrence affecting natural and engineered microbial systems. In this opinion article, we propose an integrative framework for microbial community coalescence to guide advances in our understanding of this important - yet underexplored - ecological phenomenon. We start by aligning community coalescence with the unified framework of biological invasion and enumerate commonalities and idiosyncrasies between these two analogous processes. Then, we discuss how organismal interactions and cohesive establishment affect coalescence outcomes with direct implications for community functioning. Last, we propose the use of ecological null modeling to study the interplay of ecological processes structuring community reassembly following coalescence.}, } @article {pmid37777765, year = {2023}, author = {Wen, Y and Yang, L and Wang, Z and Liu, X and Gao, M and Zhang, Y and Wang, J and He, P}, title = {Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {218}, pmid = {37777765}, issn = {2049-2618}, support = {2017YFC1600306//National Key Research and Development Program of China/ ; 2017YFC1600306//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear.

OBJECTIVE: Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon.

RESULTS: High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group.

CONCLUSIONS: For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract.}, } @article {pmid37775582, year = {2023}, author = {Samaey, A and Vázquez-Castellanos, JF and Caenepeel, C and Evenepoel, P and Vermeire, S and Raes, J and Knops, N}, title = {Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {37775582}, issn = {1432-198X}, support = {1236321N//FWO Vlaanderen/ ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels.

METHODS: We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively.

RESULTS: CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT.

CONCLUSION: FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT. A higher resolution version of the Graphical abstract is available as Supplementary information.}, } @article {pmid37774733, year = {2023}, author = {Mandal, S and Simmons, R and Ireland, G and Charlett, A and Desai, M and Coughlan, L and Powell, A and Leeman, D and Williams, C and Neill, C and O'Leary, MC and Sawyer, C and Rowley, F and Harris, C and Houlihan, C and Gordon, C and Rampling, T and Callaby, H and Hoschler, K and Cogdale, J and Renz, E and Sebastianpilli, P and Thompson, C and Talts, T and Celma, C and Davies, EA and Ahmad, S and Machin, N and Gifford, L and Moore, C and Dickson, EM and Divala, TH and Henderson, D and Li, K and Broadbent, P and Ushiro-Lumb, I and Humphreys, C and Grammatikopoulos, T and Hartley, J and Kelgeri, C and Rajwal, S and Okike, I and Kelly, DA and Guiver, M and Borrow, R and Bindra, R and Demirjian, A and Brown, KE and Ladhani, SN and Ramsay, ME and Bradley, DT and Gjini, A and Roy, K and Chand, M and Zambon, M and Watson, CH}, title = {Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.}, journal = {The Lancet. Child & adolescent health}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2352-4642(23)00215-8}, pmid = {37774733}, issn = {2352-4650}, abstract = {BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes.

METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups.

FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (β 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity.

INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation.

FUNDING: None.}, } @article {pmid37771706, year = {2023}, author = {Feng, E and Yang, X and Zhao, K and Li, Y and Zhu, H and Wang, Z and Zhang, Z}, title = {Gut microbiota is associated with spatial memory and seed-hoarding behavior of South China field mice (Apodemus draco).}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1236359}, pmid = {37771706}, issn = {1664-302X}, abstract = {BACKGROUND: Scatter-hoarding animals store food in multiple locations within their home range and rely on spatial memory for subsequent localization and retrieval. The relationship between memory and scatter-hoarding behavior has been widely demonstrated, but the association of gut microbiota with spatial memory and seed-hoarding behavior of animals remains unclear.

METHODS: In this study, by using enclosure behavior tests, memory tests including an object location test (OLT) and a novel object recognition test (NORT), and fecal microbiota transplantation (FMT) experiment, we evaluated the role of gut microbiota in affecting the memory and seed-hoarding behavior of rodents. According to their scatter-hoarding intensity, South China field mice (Apodemus draco) were divided into scatter-hoarding group (SG) and non-scatter-hoarding group (NG).

RESULTS: We found that the SG performed better than the NG in the NORT. FMT from SG donor mice altered the NG recipient mice's gut microbiota structure. Further tests demonstrated FMT from SG donor mice increased memory of NG recipient mice in laboratory tests and seed larder hoarding intensity of NG recipient mice in enclosures.

CONCLUSION: Our results suggest gut microbiota could modulate the memory and seed-hoarding behavior of animals.}, } @article {pmid37771694, year = {2023}, author = {Tang, J and Zhang, H and Yin, L and Zhou, Q and Zhang, H}, title = {The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1225991}, pmid = {37771694}, issn = {2235-2988}, mesh = {Humans ; Mice ; Animals ; *Sarcopenia/etiology ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation ; *Muscular Diseases ; Muscles ; }, abstract = {BACKGROUND: Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association.

METHODS: Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses.

RESULTS: Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota.

CONCLUSION: This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.}, } @article {pmid37771199, year = {2023}, author = {Horvath, A and Zukauskaite, K and Hazia, O and Balazs, I and Stadlbauer, V}, title = {Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?.}, journal = {Endocrinology, diabetes & metabolism}, volume = {}, number = {}, pages = {e436}, doi = {10.1002/edm2.436}, pmid = {37771199}, issn = {2398-9238}, support = {KLI741//Austrian Science Fund/ ; }, abstract = {Shifts in gut microbiome composition and metabolic disorders are associated with one another. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Diet, intake of probiotics or prebiotics and faecal microbiome transplantation (FMT) are methods to alter a person's microbiome composition. Although FMT may allow establishing a proof of concept to use microbiome modulation to treat metabolic disorders, studies show mixed results regarding the effects on metabolic parameters as well as on the composition of the microbiome. This review summarizes the current knowledge on diet, probiotics, prebiotics and FMT to treat metabolic diseases, focusing on studies that also report alterations in microbiome composition. Furthermore, clinical trial results on the effects of common drugs used to treat metabolic diseases are synopsized to highlight the bidirectional relationship between the microbiome and metabolic diseases. In conclusion, there is clear evidence that microbiome modulation has the potential to influence metabolic diseases; however, it is not possible to distinguish which intervention is the most successful. In addition, a clear commitment from all stakeholders is necessary to move forward in the direction of developing targeted interventions for microbiome modulation.}, } @article {pmid37770953, year = {2023}, author = {Zhang, M and Liu, J and Xia, Q}, title = {Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target.}, journal = {Experimental hematology & oncology}, volume = {12}, number = {1}, pages = {84}, pmid = {37770953}, issn = {2162-3619}, support = {2022ZZ01016//Shanghai Organ Transplantation Research Center/ ; 92059205//National Natural Science Foundation of China/ ; }, abstract = {Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients' response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy response and immune-related adverse events (irAEs). Unlike other -omics, the gut microbiome can serve as not only biomarkers but also potential targets for enhancing the efficacy of immunotherapy. Approaches for modulating the gut microbiome include probiotics/prebiotics supplementation, dietary interventions, fecal microbiota transplantation (FMT), and antibiotic administration. This review primarily focuses on elucidating the potential role of the gut microbiome in predicting the response to cancer immunotherapy and improving its efficacy. Notably, we explore reasons behind inconsistent findings observed in different studies, and highlight the underlying benefits of antibiotics in liver cancer immunotherapy.}, } @article {pmid37769622, year = {2023}, author = {Rossier, L and Matter, C and Burri, E and Galperine, T and Hrúz, P and Juillerat, P and Schoepfer, A and Vavricka, SR and Zahnd, N and Décosterd, N and Seibold, F}, title = {Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice.}, journal = {Swiss medical weekly}, volume = {153}, number = {}, pages = {40100}, doi = {10.57187/smw.2023.40100}, pmid = {37769622}, issn = {1424-3997}, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT.

METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre).

RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.}, } @article {pmid37764957, year = {2023}, author = {Boicean, A and Bratu, D and Fleaca, SR and Vasile, G and Shelly, L and Birsan, S and Bacila, C and Hasegan, A}, title = {Exploring the Potential of Fecal Microbiota Transplantation as a Therapy in Tuberculosis and Inflammatory Bowel Disease.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37764957}, issn = {2076-0817}, support = {contract no. 28PFE/30.12.2021//Ministerul Cercetării și Inovării/ ; }, abstract = {This review explores the potential benefits of fecal microbiota transplantation (FMT) as an adjunct treatment in tuberculosis (TB), drawing parallels from its efficacy in inflammatory bowel disease (IBD). FMT has shown promise in restoring the gut microbial balance and modulating immune responses in IBD patients. Considering the similarities in immunomodulation and dysbiosis between IBD and TB, this review hypothesizes that FMT may offer therapeutic benefits as an adjunct therapy in TB. Methods: We conducted a systematic review of the existing literature on FMT in IBD and TB, highlighting the mechanisms and potential implications of FMT in the therapeutic management of both conditions. The findings contribute to understanding FMT's potential role in TB treatment and underscore the necessity for future research in this direction to fully leverage its clinical applications. Conclusion: The integration of FMT into the comprehensive management of TB could potentially enhance treatment outcomes, reduce drug resistance, and mitigate the side effects of conventional therapies. Future research endeavors should focus on well-designed clinical trials to develop guidelines concerning the safety and short- and long-term benefits of FMT in TB patients, as well as to assess potential risks.}, } @article {pmid37764783, year = {2023}, author = {Li, L and Wu, L and Jiang, T and Liang, T and Yang, L and Li, Y and Gao, H and Zhang, J and Xie, X and Wu, Q}, title = {Lactiplantibacillus plantarum 124 Modulates Sleep Deprivation-Associated Markers of Intestinal Barrier Dysfunction in Mice in Conjunction with the Regulation of Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {18}, pages = {}, pmid = {37764783}, issn = {2072-6643}, support = {(2022B1111070006)//the Key Research and Development Program of Guangdong Province/ ; 2019QN01N107//the Department of Science and Technology of Guangdong Province/ ; 2020GDASYL-20200102003//GDAS' Project of Science and Technology Development/ ; }, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; Sleep Deprivation ; *Gastrointestinal Diseases ; *Intestinal Diseases ; Firmicutes ; Cytokines ; }, abstract = {Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.}, } @article {pmid37764082, year = {2023}, author = {Bénard, MV and Arretxe, I and Wortelboer, K and Harmsen, HJM and Davids, M and de Bruijn, CMA and Benninga, MA and Hugenholtz, F and Herrema, H and Ponsioen, CY}, title = {Anaerobic Feces Processing for Fecal Microbiota Transplantation Improves Viability of Obligate Anaerobes.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764082}, issn = {2076-2607}, support = {innovation grant 2021 - Amsterdam Gastroenterology Endocrinology Metabolism (AGEM)//University of Amsterdam/ ; }, abstract = {Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials.}, } @article {pmid37764025, year = {2023}, author = {Metafuni, E and Di Marino, L and Giammarco, S and Bellesi, S and Limongiello, MA and Sorà, F and Frioni, F and Maggi, R and Chiusolo, P and Sica, S}, title = {The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764025}, issn = {2076-2607}, abstract = {Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy.}, } @article {pmid37764005, year = {2023}, author = {Dicks, LMT}, title = {Biofilm Formation of Clostridioides difficile, Toxin Production and Alternatives to Conventional Antibiotics in the Treatment of CDI.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764005}, issn = {2076-2607}, abstract = {Clostridioides difficile is considered a nosocomial pathogen that flares up in patients exposed to antibiotic treatment. However, four out of ten patients diagnosed with C. difficile infection (CDI) acquired the infection from non-hospitalized individuals, many of whom have not been treated with antibiotics. Treatment of recurrent CDI (rCDI) with antibiotics, especially vancomycin (VAN) and metronidazole (MNZ), increases the risk of experiencing a relapse by as much as 70%. Fidaxomicin, on the other hand, proved more effective than VAN and MNZ by preventing the initial transcription of RNA toxin genes. Alternative forms of treatment include quorum quenching (QQ) that blocks toxin synthesis, binding of small anion molecules such as tolevamer to toxins, monoclonal antibodies, such as bezlotoxumab and actoxumab, bacteriophage therapy, probiotics, and fecal microbial transplants (FMTs). This review summarizes factors that affect the colonization of C. difficile and the pathogenicity of toxins TcdA and TcdB. The different approaches experimented with in the destruction of C. difficile and treatment of CDI are evaluated.}, } @article {pmid37762509, year = {2023}, author = {Zabolotneva, AA and Gaponov, AM and Roumiantsev, SA and Vasiliev, IY and Grigoryeva, TV and Kit, OI and Zlatnik, EY and Maksimov, AY and Goncharova, AS and Novikova, IA and Appolonova, SA and Markin, PA and Shestopalov, AV}, title = {Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, doi = {10.3390/ijms241814206}, pmid = {37762509}, issn = {1422-0067}, abstract = {Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.}, } @article {pmid37761817, year = {2023}, author = {Carapeto, S and Cunha, E and Serrano, I and Pascoal, P and Pereira, M and Abreu, R and Neto, S and Antunes, B and Dias, R and Tavares, L and Oliveira, M}, title = {Effect of the Administration of a Lyophilised Faecal Capsules on the Intestinal Microbiome of Dogs: A Pilot Study.}, journal = {Genes}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/genes14091676}, pmid = {37761817}, issn = {2073-4425}, support = {UIDB/00276/2020//Fundação para a Ciência e Tecnologia/ ; LA/P/0059/2020//AL4AnimalS/ ; }, abstract = {Faecal Microbiota Transplantation (FMT) is a promising strategy for modulating the gut microbiome. We aimed to assess the effect of the oral administration of capsules containing lyophilised faeces on dogs with diarrhoea for 2 months as well as evaluate their long-term influence on animals' faecal consistency and intestinal microbiome. This pilot study included five dogs: two used as controls and three with diarrhoea. Animals were evaluated for four months by performing a monthly faecal samples collection and physical examination, which included faecal consistency determination using the Bristol scale. The total number of viable bacteria present in the capsules was quantified and their bacterial composition was determined by 16S rRNA gene sequencing, which was also applied to the faecal samples. During the assay, no side effects were reported. Animals' faecal consistency improved and, after ending capsules administration, Bristol scale values remained stable in two of the three animals. The animals' microbiome gradually changed toward a composition associated with a balanced microbiota. After FMT, a slight shift was observed in its composition, but the capsules' influence remained evident during the 4-month period. Capsules administration seems to have a positive effect on the microbiota modulation; however, studies with more animals should be performed to confirm our observations.}, } @article {pmid37761327, year = {2023}, author = {Stojic, J and Kukla, M and Grgurevic, I}, title = {The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, doi = {10.3390/diagnostics13182960}, pmid = {37761327}, issn = {2075-4418}, abstract = {Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.}, } @article {pmid37760856, year = {2023}, author = {Wu, L and Lin, ZH and Lu, XJ and Hu, X and Zhong, HJ and Lin, DJ and Liu, T and Xu, JT and Lin, WY and Wu, QP and He, XX}, title = {Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/biomedicines11092415}, pmid = {37760856}, issn = {2227-9059}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; 2021KCXTD025//Guangdong Innovation Research Team for Higher Education/ ; }, abstract = {BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients.

METHODS: The changes in body mass index (BMI = weight (kg)/height (m)[2]), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics.

RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism.

CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.}, } @article {pmid37756370, year = {2023}, author = {Zhou, J and Hao, J and Zhong, Z and Yang, J and Lv, T and Zhao, B and Lin, H and Chi, J and Guo, H}, title = {Fecal microbiota transplantation in mice exerts a protective effect against doxorubicin-induced cardiac toxicity by regulating Nrf2-mediated cardiac mitochondrial fission and fusion.}, journal = {Antioxidants & redox signaling}, volume = {}, number = {}, pages = {}, doi = {10.1089/ars.2023.0355}, pmid = {37756370}, issn = {1557-7716}, abstract = {AIMS: The relationship between gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combatting doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood.

RESULTS: During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite Indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieves this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing ROS production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress.

INNOVATION: FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart.

CONCLUSION: FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.}, } @article {pmid37756322, year = {2023}, author = {Stefansson, M and Bladh, O and Flink, O and Skolling, O and Ekre, HP and Rombo, L and Engstrand, L and Ursing, J}, title = {Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0292132}, pmid = {37756322}, issn = {1932-6203}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking.

AIMS: To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics.

METHOD: Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed.

RESULTS: Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8).

CONCLUSION: Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo.

TRIAL REGISTRATION: EudraCT 2017-002418-30.}, } @article {pmid37756083, year = {2023}, author = {Rojas, CA and Entrolezo, Z and Jarett, JK and Jospin, G and Kingsbury, DD and Martin, A and Eisen, JA and Ganz, HH}, title = {Microbiome Responses to Fecal Microbiota Transplantation in Cats with Chronic Digestive Issues.}, journal = {Veterinary sciences}, volume = {10}, number = {9}, pages = {}, doi = {10.3390/vetsci10090561}, pmid = {37756083}, issn = {2306-7381}, support = {AB-1001//AnimalBiome/ ; }, abstract = {There is growing interest in the application of fecal microbiota transplants (FMTs) in small animal medicine, but there are few published studies that have tested their effects in the domestic cat (Felis catus). Here we use 16S rRNA gene sequencing to examine fecal microbiome changes in 46 domestic cats with chronic digestive issues that received FMTs using lyophilized stool that was delivered in oral capsules. Fecal samples were collected from FMT recipients before and two weeks after the end of the full course of 50 capsules, as well as from their stool donors (N = 10), and other healthy cats (N = 113). The fecal microbiomes of FMT recipients varied with host clinical signs and dry kibble consumption, and shifts in the relative abundances of Clostridium, Collinsella, Megamonas, Desulfovibrio and Escherichia were observed after FMT. Overall, donors shared 13% of their bacterial amplicon sequence variants (ASVs) with FMT recipients and the most commonly shared ASVs were classified as Prevotella 9, Peptoclostridium, Bacteroides, and Collinsella. Lastly, the fecal microbiomes of cats with diarrhea became more similar to the microbiomes of age-matched and diet-matched healthy cats compared to cats with constipation. Overall, our results suggest that microbiome responses to FMT may be modulated by the FMT recipient's initial presenting clinical signs, diet, and their donor's microbiome.}, } @article {pmid37754772, year = {2023}, author = {Liu, X and Yang, M and Liu, R and Zhou, F and Zhu, H and Wang, X}, title = {The impact of Parkinson's disease-associated gut microbiota on the transcriptome in Drosophila.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0017623}, doi = {10.1128/spectrum.00176-23}, pmid = {37754772}, issn = {2165-0497}, abstract = {Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and many studies have confirmed that the disorder of gut microbiota is involved in the pathophysiological process of PD. However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation (FMT) in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We first constructed rotenone-induced PD models in Drosophila followed by FMT in different groups. Microbial analysis by 16S rDNA sequencing showed that gut microbiota from PD Drosophila could affect bacterial structure of normal Drosophila, and gut microbiota from normal Drosophila could affect bacterial structure of PD Drosophila. Transcriptome analysis revealed that PD-associated gut microbiota influenced expression patterns of genes enriched in neuroactive ligand-receptor interaction, lysosome, and diverse metabolic pathways. Importantly, to verify our findings, we transplanted Drosophila with fecal samples from clinical PD patients. Compared to the control, Drosophila transplanted with fecal samples from PD patients had reduced microbiota Acetobacter and Lactobacillus, and differentially expressed genes enriched in diverse metabolic pathways. In summary, our results reveal the influence of PD-associated gut microbiota on host gene expression, and this study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis. IMPORTANCE Gut microbiota plays important roles in regulating host gene expression and physiology through complex mechanisms. Recently, it has been suggested that disorder of gut microbiota is involved in the pathophysiological process of Parkinson's disease (PD). However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We also verified our findings by transplanting Drosophila with fecal samples from clinical PD patients. Our results demonstrated that PD-associated gut microbiota can induce differentially expressed genes enriched in diverse metabolic pathways. This study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis.}, } @article {pmid37754239, year = {2023}, author = {Malnick, SDH and Ohayon Michael, S}, title = {The Intestinal Microbiome and the Metabolic Syndrome-How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD).}, journal = {Current issues in molecular biology}, volume = {45}, number = {9}, pages = {7197-7211}, pmid = {37754239}, issn = {1467-3045}, abstract = {Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.}, } @article {pmid37753568, year = {2023}, author = {Liu, Y and Zhang, P and Sheng, H and Xu, D and Li, D and An, L}, title = {16S rRNA gene sequencing and machine learning reveal correlation between drug abuse and human host gut microbiota.}, journal = {Addiction biology}, volume = {28}, number = {10}, pages = {e13311}, doi = {10.1111/adb.13311}, pmid = {37753568}, issn = {1369-1600}, support = {41830321//Key Program National Natural Science Foundation of China/ ; 17ZD2WA017//National Science and Technology Major Project in Gansu/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; China ; *Substance-Related Disorders ; Citrates ; }, abstract = {Over the past few years, there has been increasing evidence highlighting the strong connection between gut microbiota and overall well-being of the host. This has led to a renewed emphasis on studying and addressing substance use disorder from the perspective of brain-gut axis. Previous studies have suggested that alcohol, food, and cigarette addictions are strongly linked to gut microbiota and faecal microbiota transplantation or the use of probiotics achieved significant efficacy. Unfortunately, little is known about the relationship between drug abuse and gut microbiota. This paper aims to reveal the potential correlation between gut microbiota and drug abuse and to develop an accurate identification model for drug-related faeces samples by machine learning. Faecal samples were collected from 476 participants from three regions in China (Shanghai, Yunnan, and Shandong). Their gut microbiota information was obtained using 16S rRNA gene sequencing, and a substance use disorder identification model was developed by machine learning. Analysis revealed a lower diversity and a more homogeneous gut microbiota community structure among participants with substance use disorder. Bacteroides, Prevotella_9, Faecalibacterium, and Blautia were identified as important biomarkers associated with substance use disorder. The function prediction analysis revealed that the citrate and reductive citrate cycles were significantly upregulated in the substance use disorder group, while the shikimate pathway was downregulated. In addition, the machine learning model could distinguish faecal samples between substance users and nonsubstance users with an AUC = 0.9, indicating its potential use in predicting and screening individuals with substance use disorder within the community in the future.}, } @article {pmid37753524, year = {2023}, author = {Ejtahed, HS and Parsa, M and Larijani, B}, title = {Ethical challenges in conducting and the clinical application of human microbiome research.}, journal = {Journal of medical ethics and history of medicine}, volume = {16}, number = {}, pages = {5}, pmid = {37753524}, issn = {2008-0387}, } @article {pmid37753364, year = {2023}, author = {Gulumbe, BH and Abdulrahim, A}, title = {Pushing the frontiers in the fight against antimicrobial resistance: the potential of fecal and maggot therapies.}, journal = {Future science OA}, volume = {9}, number = {10}, pages = {FSO899}, pmid = {37753364}, issn = {2056-5623}, abstract = {The escalating crisis of antimicrobial resistance (AMR) warrants innovative therapeutic strategies. Fecal microbiota transplantation (FMT) and maggot debridement therapy (MDT) represent paradigm-shifting approaches, leveraging biological systems to mitigate AMR. FMT restores a healthy gut microbiome, providing a biotherapeutic counter to pathogenic bacteria, thereby reducing reliance on traditional antibiotics. Conversely, MDT, a form of bio-debridement, utilizes the antimicrobial secretions of maggots to cleanse wounds and eliminate resistant bacteria. Despite the promise these therapies hold, their broader clinical adoption faces multifaceted challenges including the need for rigorous scientific substantiation, standardized protocols, deepened understanding of mechanisms of action, and surmounting regulatory and public acceptance barriers. However, their potential integration with precision medicine could revolutionize disease management, particularly with antibiotic-resistant infections.}, } @article {pmid37752615, year = {2023}, author = {Jin, Z and Yang, Y and Cao, Y and Wen, Q and Xi, Y and Cheng, J and Zhao, Q and Weng, J and Hong, K and Jiang, H and Hang, J and Zhang, Z}, title = {The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {212}, pmid = {37752615}, issn = {2049-2618}, support = {2022YFC2702600//National Key Research and Development Program of China/ ; 20220484160//Beijing Nova Program/ ; 7222208//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: Aging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored.

RESULTS: Here, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression.

CONCLUSIONS: Our results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice. Video Abstract.}, } @article {pmid37752426, year = {2023}, author = {Lapauw, L and Dupont, J and Amini, N and Vercauteren, L and Verschueren, S and Tournoy, J and Raes, J and Gielen, E}, title = {Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.}, journal = {BMC geriatrics}, volume = {23}, number = {1}, pages = {599}, pmid = {37752426}, issn = {1471-2318}, abstract = {BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia.

METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1β and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM.

DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM.

TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.}, } @article {pmid37752225, year = {2023}, author = {Luo, Y and Liu, C and Luo, Y and Zhang, X and Li, J and Hu, C and Yang, S}, title = {Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis.}, journal = {Cellular & molecular immunology}, volume = {}, number = {}, pages = {}, pmid = {37752225}, issn = {2042-0226}, support = {81802460//National Natural Science Foundation of China (National Science Foundation of China)/ ; CSTB2022NSCQ-MSX0184//Natural Science Foundation of Chongqing (Natural Science Foundation of Chongqing Municipality)/ ; }, abstract = {Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4[+] T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for the treatment of IBD.}, } @article {pmid37750481, year = {2023}, author = {Gryschek, RCB and Corral, MA and Sitta, RB and Gottardi, M and Pierrotti, LC and Costa, SF and Abdala, E and Chieffi, PP and de Paula, FM}, title = {Strongyloides infection screening in transplant candidates: What is the best strategy?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14153}, doi = {10.1111/tid.14153}, pmid = {37750481}, issn = {1399-3062}, support = {2010/51110-2//Fundação de Amparo à Pesquisa do EStado de São Paulo (FAPESP)/ ; 2013/04236-9//Fundação de Amparo à Pesquisa do EStado de São Paulo (FAPESP)/ ; }, abstract = {BACKGROUND: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern.

METHODS: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates.

RESULTS: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR).

CONCLUSION: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.}, } @article {pmid37749611, year = {2023}, author = {Liu, A and Liang, X and Wang, W and Wang, C and Song, J and Guo, J and Sun, D and Wang, D and Song, M and Qian, J and Zhang, X}, title = {Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis.}, journal = {Stem cell research & therapy}, volume = {14}, number = {1}, pages = {271}, pmid = {37749611}, issn = {1757-6512}, support = {82270545//National Natural Science Foundation of China/ ; 82070563//National Natural Science Foundation of China/ ; H2020206497//Natural Science Foundation of Hebei Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; *Colitis/chemically induced/therapy ; *Inflammatory Bowel Diseases ; *Mesenchymal Stem Cells ; Fatty Acids, Volatile ; Inflammation ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.

METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4[+]T homeostasis.

RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.

CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.}, } @article {pmid37746903, year = {2023}, author = {Verhoef, JI and Klont, E and van Overveld, FJ and Rijkers, GT}, title = {The long and winding road of faecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy.}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/14737140.2023.2262765}, pmid = {37746903}, issn = {1744-8328}, abstract = {INTRODUCTION: Immune checkpoint inhibition (ICI) therapy has revolutionized the treatment of cancer. Inhibitory molecules, either on the tumor or on cells of the immune system, are blocked, allowing the immune system of the patient to attack and eradicate the tumor. Not all patients respond to ICI therapy, and response or non-response has been associated with composition of gut microbiota.

AREA COVERED: Fecal microbiota transplantation (FMT) is used as adjunctive therapy in order to improve the outcome of ICI. ClinicalTrials.gov, and other databases were searched (October 2022) for studies dealing with gut microbiota modification and the outcome of ICI.

EXPERT OPINION: There is ample evidence for the beneficial effect of FMT on the outcome of ICI therapy for cancer, especially melanoma. Progress is being made in the unraveling of the mechanisms by which microbiota and their metabolites (butyrate and the tryptophan metabolite indole-3-aldehyde) interact with the mucosal immune system of the host. A better understanding of the mechanisms involved will allow the identification of key bacterial species which mediate the effect of FMT. Promising species are Faecalibacterium prausnitzii, Eubacterium rectale, Bifidobacterium adolescentis, B. bifidum, and B. longum, because they are important direct and indirect butyrate producers.}, } @article {pmid37743861, year = {2023}, author = {Hu, X and Jin, H and Yuan, S and Ye, T and Chen, Z and Kong, Y and Liu, J and Xu, K and Sun, J}, title = {Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1254610}, pmid = {37743861}, issn = {2235-2988}, mesh = {Animals ; Mice ; *Brain-Gut Axis ; Neuroinflammatory Diseases ; Fecal Microbiota Transplantation ; *Brain Injuries, Traumatic/therapy ; Cytokines ; Disease Models, Animal ; }, abstract = {INTRODUCTION: Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota-gut-brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota-gut-brain axis.

METHODS: The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured.

RESULTS: Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice.

CONCLUSION: These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota-gut-brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.}, } @article {pmid37742728, year = {2023}, author = {Ciernikova, S and Sevcikova, A and Drgona, L and Mego, M}, title = {Modulating the gut microbiota by probiotics, prebiotics, postbiotics, and fecal microbiota transplantation: An emerging trend in cancer patient care.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {}, number = {}, pages = {188990}, doi = {10.1016/j.bbcan.2023.188990}, pmid = {37742728}, issn = {1879-2561}, abstract = {Treatment resistance, together with acute and late adverse effects, represents critical issues in the management of cancer patients. Promising results from preclinical and clinical research underline the emerging trend of a microbiome-based approach in oncology. Favorable bacterial species and higher gut diversity are associated with increased treatment efficacy, mainly in chemo- and immunotherapy. On the other hand, alterations in the composition and activity of gut microbial communities are linked to intestinal dysbiosis and contribute to high treatment-induced toxicity. In this Review, we provide an overview of studies concerning gut microbiota modulation in patients with solid and hematologic malignancies with a focus on probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Targeting the gut microbiome might bring clinical benefits and improve patient outcomes. However, a deeper understanding of mechanisms and large clinical trials concerning microbiome and immunological profiling is warranted to identify safe and effective ways to incorporate microbiota-based interventions in routine clinical practice.}, } @article {pmid37741298, year = {2023}, author = {Liu, Z and Sun, M and Jin, C and Sun, X and Feng, F and Niu, X and Wang, B and Zhang, Y and Wang, J}, title = {Naringenin confers protection against experimental autoimmune encephalomyelitis through modulating the gut-brain axis: A multi-omics analysis.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109448}, doi = {10.1016/j.jnutbio.2023.109448}, pmid = {37741298}, issn = {1873-4847}, abstract = {Multiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequence to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.}, } @article {pmid37741061, year = {2023}, author = {Yue, C and Luan, W and Gu, H and Qiu, D and Ding, X and Liu, P and Wang, X and Hashimoto, K and Yang, JJ}, title = {The role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in chronic inflammatory pain and comorbid spatial working memory impairment in complete Freund's adjuvant mice.}, journal = {Journal of psychiatric research}, volume = {166}, number = {}, pages = {61-73}, doi = {10.1016/j.jpsychires.2023.09.003}, pmid = {37741061}, issn = {1879-1379}, abstract = {Chronic inflammatory pain (CIP) is a common public medical problem, often accompanied by memory impairment. However, the mechanisms underlying CIP and comorbid memory impairment remain elusive. This study aimed to examine the role of the gut-microbiota-brain axis in CIP and comorbid memory impairment in mice treated with complete Freund's adjuvant (CFA). 16S rRNA analysis showed the altered diversity of gut microbiota from day 1 to day 14 after CFA injection. Interestingly, fecal microbiota transplantation (FMT) from healthy naive mice ameliorated comorbidities, such as mechanical allodynia, thermal hyperalgesia, spatial working memory impairment, neuroinflammation, and abnormal composition of gut microbiota in the CFA mice. Additionally, subdiaphragmatic vagotomy (SDV) blocked the onset of these comorbidities. Interestingly, the relative abundance of the bacterial genus or species was also correlated with these comorbidities after FMT or SDV. Therefore, our results suggest that the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve is crucial for the development of CIP and comorbid spatial working memory impairment in CFA mice.}, } @article {pmid37736702, year = {2023}, author = {Kragsnaes, MS and Miguens Blanco, J and Mullish, BH and Contreras-Serrano, JI and Kjeldsen, J and Horn, HC and Pedersen, JK and Munk, HL and Nilsson, AC and Salam, A and Lewis, MR and Chekmeneva, E and Kristiansen, K and Marchesi, JR and Ellingsen, T}, title = {Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.}, journal = {ACR open rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acr2.11604}, pmid = {37736702}, issn = {2578-5745}, support = {21228/VAC_/Versus Arthritis/United Kingdom ; }, abstract = {OBJECTIVE: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).

METHODS: This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using [1] H Nuclear Magnetic Resonance.

RESULTS: Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).

CONCLUSION: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.}, } @article {pmid37734581, year = {2023}, author = {Yau, YK and Lau, LHS and Lui, RNS and Wong, SH and Guo, CL and Mak, JWY and Ching, JYL and Ip, M and Kamm, MA and Rubin, DT and Chan, PKS and Chan, FKL and Ng, SC}, title = {Long-term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data over Eight Years from the Hong Kong FMT Registry.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2023.09.001}, pmid = {37734581}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong.

METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short-to-long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics.

RESULTS: Overall, 123 subjects (median age 53 years; range 13-90; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 months (range, 1-57.9). The most common indication for FMT was type 2 diabetes mellitus (DM). The most common short-term adverse events within one month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, DM or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched controls.

CONCLUSION: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.}, } @article {pmid37733476, year = {2023}, author = {Kashyap, Y and Wang, ZJ}, title = {Gut microbiota dysbiosis alters chronic pain behaviors in a humanized transgenic mouse model of sickle cell disease.}, journal = {Pain}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.pain.0000000000003034}, pmid = {37733476}, issn = {1872-6623}, support = {R35 HL140021/HL/NHLBI NIH HHS/United States ; }, abstract = {Pain is the most common symptom experienced by patients with sickle cell disease (SCD) throughout their lives and is the main cause of hospitalization. Despite the progress that has been made towards understanding the disease pathophysiology, major gaps remain in the knowledge of SCD pain, the transition to chronic pain, and effective pain management. Recent evidence has demonstrated a vital role of gut microbiota in pathophysiological features of SCD. However, the role of gut microbiota in SCD pain is yet to be explored. We sought to evaluate the compositional differences in the gut microbiota of transgenic mice with SCD and nonsickle control mice and investigate the role of gut microbiota in SCD pain by using antibiotic-mediated gut microbiota depletion and fecal material transplantation (FMT). The antibiotic-mediated gut microbiota depletion did not affect evoked pain but significantly attenuated ongoing spontaneous pain in mice with SCD. Fecal material transplantation from mice with SCD to wild-type mice resulted in tactile allodynia (0.95 ± 0.17 g vs 0.08 ± 0.02 g, von Frey test, P < 0.001), heat hyperalgesia (15.10 ± 0.79 seconds vs 8.68 ± 1.17 seconds, radiant heat, P < 0.01), cold allodynia (2.75 ± 0.26 seconds vs 1.68 ± 0.08 seconds, dry ice test, P < 0.01), and anxiety-like behaviors (Elevated Plus Maze Test, Open Field Test). On the contrary, reshaping gut microbiota of mice with SCD with FMT from WT mice resulted in reduced tactile allodynia (0.05 ± 0.01 g vs 0.25 ± 0.03 g, P < 0.001), heat hyperalgesia (5.89 ± 0.67 seconds vs 12.25 ± 0.76 seconds, P < 0.001), and anxiety-like behaviors. These findings provide insights into the relationship between gut microbiota dysbiosis and pain in SCD, highlighting the importance of gut microbial communities that may serve as potential targets for novel pain interventions.}, } @article {pmid37731574, year = {2023}, author = {Zyoud, SH and Shakhshir, M and Abushanab, AS and Koni, A and Shahwan, M and Jairoun, AA and Abu Taha, A and Al-Jabi, SW}, title = {Unveiling the hidden world of gut health: Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota.}, journal = {World journal of clinical cases}, volume = {11}, number = {26}, pages = {6132-6146}, pmid = {37731574}, issn = {2307-8960}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in gastrointestinal and overall health. Randomized clinical trials (RCTs) play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.

AIM: To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.

METHODS: Using bibliometric tools, a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota, spanning the years 2003 to 2022. The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications. The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.

RESULTS: A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022. The number of publications showed a notable increase over time, with a positive correlation (R[2] = 0.978, P < 0.001). China (n = 276, 26.01%), the United States (n = 254, 23.94%), and the United Kingdom (n = 97, 9.14%) were the leading contributing countries. Københavns Universitet (n = 38, 3.58%) and Dankook University (n = 35, 3.30%) were the top active institutions. The co-occurrence analysis shows current gut microbiota research trends and important topics, such as obesity interventions targeting the gut microbiota, the efficacy and safety of fecal microbiota transplantation, and the effects of dietary interventions on humans.

CONCLUSION: The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota. This study provides valuable insight into research trends, identifies key players, and outlines potential future directions in this field. Additionally, the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.}, } @article {pmid37730588, year = {2023}, author = {Wang, H and Liu, S and Xie, L and Wang, J}, title = {Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms.}, journal = {BMC pediatrics}, volume = {23}, number = {1}, pages = {476}, pmid = {37730588}, issn = {1471-2431}, mesh = {Female ; Male ; Child ; Humans ; Child, Preschool ; *Gastrointestinal Microbiome ; *Autism Spectrum Disorder ; *Microbiota ; Anxiety ; Constipation ; }, abstract = {BACKGROUND: Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it's essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.

METHODS: In this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.

RESULTS: The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.

CONCLUSIONS: Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.}, } @article {pmid37727718, year = {2023}, author = {Del Giglio, A and Atui, FC}, title = {Fecal transplantation in patient with metastatic melanoma refractory to immunotherapy: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {24}, pages = {5830-5834}, pmid = {37727718}, issn = {2307-8960}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of metastatic melanoma, but a significant proportion of patients still experience treatment resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.

CASE SUMMARY: We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with anti-programmed death-ligand 1 (PD-L1) immunotherapy (pembrolizumab). After failing multiple lines of treatment, the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy. Following FMT, the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease. Despite a subsequent recurrence in the small bowel that was resected, the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.

CONCLUSION: The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.}, } @article {pmid37727287, year = {2023}, author = {Li, Y and Li, X and Nie, C and Wu, Y and Luo, R and Chen, C and Niu, J and Zhang, W}, title = {Effects of two strains of Lactobacillus isolated from the feces of calves after fecal microbiota transplantation on growth performance, immune capacity, and intestinal barrier function of weaned calves.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1249628}, pmid = {37727287}, issn = {1664-302X}, abstract = {INTRODUCTION: Weaning stress seriously affects the welfare of calves and causes huge economic losses to the cattle breeding industry. Probiotics play an important role in improving animal growth performance, enhancing immune function, and improving gut microbiota. The newly isolated strains of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 have shown potential as probiotics. Here, we studied the probiotic properties of these two strains on weaned calves.

METHODS: Forty calves were randomly assigned to four groups before weaning, with 10 calves in each group, control group (Ctrl group), L. reuteri L81 supplementation group (2 g per day per calf), L. johnsonii L29 supplementation group (2 g per day per calf), L. reuteri L81 and L. johnsonii L29 composite group (2 g per day per calf), and the effects of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 supplementation on growth performance, immune status, antioxidant capacity, and intestinal barrier function of weaned calves were evaluated.

RESULTS: The results showed that probiotics supplementation increased the average daily weight gain of calves after weaning, reduced weaning diarrhea index (p < 0.05), and increased serum IgA, IgM, and IgG levels (p < 0.05). L. reuteri L81 supplementation significantly decreased IL-6, increased IL-10 and superoxide dismutase (SOD) levels at 21 d after weaning (p < 0.05). Moreover, probiotics supplementation significantly decreased serum endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) levels at different time points (p < 0.05). In addition, supplementation with L. reuteri L81 significantly reduced the crypt depth and increased the ratio of villus height to crypt depth (p < 0.05) in the ileum, increased gene expression of tight junction protein ZO-1, Claudin-1 and Occludin in jejunum and ileum mucosa, reduced the gene expression of INF- γ in ileum mucosa and IL-8 in jejunum mucosa, and increased the abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, Oscillospira, etc.

DISCUSSION: verall, these results showed that the two strains isolated from cattle feces after low concentration fecal microbiota transplantation improved the growth performance, immune performance, antioxidant capacity, and intestinal barrier function of weaned calves, indicating their potential as supplements to alleviate weaning diarrhea in calves.}, } @article {pmid37725892, year = {2023}, author = {Shang, S and Zhu, J and Liu, X and Wang, W and Dai, T and Wang, L and Li, B}, title = {The Impacts of Fecal Microbiota Transplantation from Same Sex on the Symptoms of Ulcerative Colitis Patients.}, journal = {Polish journal of microbiology}, volume = {72}, number = {3}, pages = {247-268}, pmid = {37725892}, issn = {2544-4646}, mesh = {Adolescent ; Humans ; Female ; Male ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Prospective Studies ; RNA, Ribosomal, 16S ; Abdominal Pain ; Bifidobacterium ; Diarrhea ; *Fabaceae ; Lactobacillus ; }, abstract = {We aimed to compare the clinical efficacy of fecal microbiota transplantation (FMT) from the same sex on ulcerative colitis (UC) patients. A total of 272 UC patients were selected in the prospective clinical study, which incorporated four distinct groups, each comprising male and female patients, who were either receiving FMT or placebo, respectively. FMT was performed by sending the gut microbiota of healthy female or male adolescents to the same gender patients via gastroscope three times (one time/three weeks), and a placebo was used with an equal volume of saline. Abdominal pain, diarrhea, thick bloody stool, intestinal mucosal lesion, and Mayo scores were measured. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. The changes of intestinal flora were detected by the 16S rRNA sequencing. FMT reduced the scores of diarrhea, abdominal pain, mucosal lesion, and Mayo, SAS, and SDS in UC patients compared to the placebo group (p < 0.05). Clostridiales and Desulfovibrionaceae were dominant in gut microbiota from male patients and were reduced after FMT. Meanwhile, the abundance of Prevotella, Lactobacillus, and Bifidobacterium was increased in the male group. Female patients had a higher abundance of Escherichia-Shigella, Desulfovibrionaceae, and Staphylococcaceae before FMT, and it was reduced after FMT. Meanwhile, the abundance of Porphyromonadaceae, Prevotella, Lactobacillus, and Bifidobacterium was increased in the female group. There were no significant changes for the species in the corresponding placebo groups. FMT improved the UC symptoms of male and female patients, which may be associated with different gut microbiota changes.}, } @article {pmid36946907, year = {2023}, author = {Wood, N and Propst, K and Yao, M and Ferrando, CA}, title = {Fecal Microbiota Transfer for Clostridium difficile Infection and Its Effects on Recurrent Urinary Tract Infection.}, journal = {Urogynecology (Philadelphia, Pa.)}, volume = {29}, number = {10}, pages = {814-826}, pmid = {36946907}, issn = {2771-1897}, mesh = {Humans ; Female ; Fecal Microbiota Transplantation ; Retrospective Studies ; Treatment Outcome ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/epidemiology ; *Urinary Tract Infections/epidemiology ; }, abstract = {IMPORTANCE: Recurrent urinary tract infection (rUTI) poses a significant management challenge, and fecal microbiota transfer (FMT) has been shown in a limited manner to positively effect rUTI.

OBJECTIVES: The objective of this study was to compare UTI rates after FMT for Clostridium difficile infection (CDI) in patients with previously diagnosed rUTI and patients without a previous diagnosis of rUTI.

STUDY DESIGN: This was a retrospective cohort study of female patients who underwent FMT between 2015 and 2020 and were identified from a database at a tertiary care referral center. The electronic medical record was queried for demographic and UTI characteristics in the 3 years before and 5 years after FMT, which were compared between patients with or without a preexisting history of rUTI.

RESULTS: One hundred thirty-five patients were included, 17 of whom had a preexisting history of rUTI. The median number of culture-proven UTIs was 1 in the rUTI group versus 0 in the non-rUTI group both in the 1 year (P = 0.003) and 3 years (P < 0.001) before FMT. Most UTIs before and after FMT were Escherichia coli UTIs (53.8%) and carried some antibiotic resistance (54.6%). Comparatively, in the year after FMT, there were no differences between groups in UTI frequency or antibiotic administration (0 [0-1] vs 0.5 [0-1], P = 0.28). A trend toward decreased frequency of UTI in the 1 year after FMT was seen in the rUTI group. On survival analysis, there was a nonsignificant decrease in the 3-year UTI-free rate for the rUTI group compared with the non-rUTI group (76.5% vs 90.1%, P = 0.07).

CONCLUSIONS: Patients with recurrent UTI undergoing FMT for recurrent CDI experienced a trend toward a decrease in frequency of UTI after FMT.}, } @article {pmid37721283, year = {2024}, author = {Cui, Y and Liu, J and Lei, X and Liu, S and Chen, H and Wei, Z and Li, H and Yang, Y and Zheng, C and Li, Z}, title = {Dual-directional regulation of spinal cord injury and the gut microbiota.}, journal = {Neural regeneration research}, volume = {19}, number = {3}, pages = {548-556}, doi = {10.4103/1673-5374.380881}, pmid = {37721283}, issn = {1673-5374}, abstract = {There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury. This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury. Our research identified three key points. First, the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury. Second, following spinal cord injury, weakened intestinal peristalsis, prolonged intestinal transport time, and immune dysfunction of the intestine caused by abnormal autonomic nerve function, as well as frequent antibiotic treatment, may induce gut dysbiosis. Third, the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury; cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system. Fecal microbiota transplantation, probiotics, dietary interventions, and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota. Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.}, } @article {pmid37714338, year = {2023}, author = {Liu, D and Gao, X and Huang, X and Fan, Y and Wang, YE and Zhang, Y and Chen, X and Wen, J and He, H and Hong, Y and Liang, Y and Zhang, Y and Liu, Z and Chen, S and Li, X}, title = {Moderate altitude exposure impacts host fasting blood glucose and serum metabolome by regulation of the intestinal flora.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {167016}, doi = {10.1016/j.scitotenv.2023.167016}, pmid = {37714338}, issn = {1879-1026}, abstract = {Moderate altitude exposure has shown beneficial effects on diabetes incidence but the underlying mechanisms are not understood. Our study aimed to investigate how the human gut microbiome impacted the serum metabolome and associated with glucose homeostasis in healthy Chinese individuals upon moderate-altitude exposure. Faecal microbiome composition was assessed using shotgun metagenomic sequencing. Serum metabolome was acquired by untargeted metabolomics technology, and amino acids (AAs) and propionic acid in serum were quantified by targeted metabolomics technology. The results indicated that the moderate-altitude exposed individuals presented lowered fasting blood glucose (FBG) and propionic acid, increased circulating l-Glutamine but decreased L-Glutamate and L-Valine, which correlated with enriched Bacteroidetes and decreased Proteobacteria. Additionally, the silico causality associations among gut microbiota, serum metabolome and host FBG were analyzed by mediation analysis. It showed that increased Bacteroides ovatus (B. ovatus) and decreased Escherichia coli (E. coli) were identified as the main antagonistic species driving the association between L-Glutamate and FBG in silico causality. Furthermore, the high-fat diet (HFD) fed mice subjected to faecal microbiota transplantation (FMT) were applied to validate the cause-in-fact effects of gut microbiota on the beneficial glucose response. We found that microbiome in the moderate-altitude exposed donor could predict the extent of the FBG response in recipient mice, which showed lowered FBG, L-Glutamate and Firmicutes/Bacteroidetes ratio. Our findings suggest that moderate-altitude exposure targeting gut microbiota and circulating metabolome, may pave novel avenues to counter dysglycemia.}, } @article {pmid37724079, year = {2021}, author = {Cheng, CK and Huang, Y}, title = {The gut-cardiovascular connection: new era for cardiovascular therapy.}, journal = {Medical review (Berlin, Germany)}, volume = {1}, number = {1}, pages = {23-46}, pmid = {37724079}, issn = {2749-9642}, abstract = {Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.}, } @article {pmid37712213, year = {2023}, author = {Mahroum, N and Seida, R and Shoenfeld, Y}, title = {Triggers and regulation: the gut microbiome in rheumatoid arthritis.}, journal = {Expert review of clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1080/1744666X.2023.2260103}, pmid = {37712213}, issn = {1744-8409}, abstract = {INTRODUCTION: Rheumatoid arthritis is a chronic inflammatory disease marked by systemic symptoms and joint degeneration. Interestingly, the development and progression of rheumatoid arthritis have been linked to the microbiome, notably the gut microbiome. Dysbiosis, an alteration in the gut microbiome, has been connected to the etiology and pathogenesis of rheumatoid arthritis. For instance, dysbiosis increases intestinal permeability and promotes the movement of bacteria and its products, which in turn triggers and aggravates systemic inflammation.

AREAS COVERED: The correlation between the gut microbiome and RA. Triggers of RA including dysbiosis. The therapeutic potential of the gut microbiome in RA due to its critical function in influencing the immune response. The fecal microbiota transplantation (FMT), a therapeutic strategy that involves the transfer of healthy fecal microbiota from a donor to a recipient, has produced encouraging results in the treatment of several autoimmune illnesses, including rheumatoid arthritis.

EXPERT OPINION: The role of the gut microbiome in RA is critical, and serves as a basis for the etiology, pathogenesis, as well as having therapeutic implications. In our opinion, FMT is an excellent example for this correlation. Still, more investigations and well-designed studied are needed in order to make firm conclusions and recommendations.}, } @article {pmid37712178, year = {2023}, author = {Sfanos, KS}, title = {Intratumoral Bacteria as Mediators of Cancer Immunotherapy Response.}, journal = {Cancer research}, volume = {83}, number = {18}, pages = {2985-2986}, doi = {10.1158/0008-5472.CAN-23-1857}, pmid = {37712178}, issn = {1538-7445}, mesh = {Humans ; Animals ; Mice ; *Esophageal Squamous Cell Carcinoma ; *Esophageal Neoplasms/therapy ; Immunotherapy ; *Microbiota ; Bacteria ; Tumor Microenvironment ; }, abstract = {Multiple lines of evidence spanning from animal models to human clinical trials indicate that the microbiome influences cancer immunotherapy response. Whereas initial studies focused exclusively on the gastrointestinal (gut) microbiota-tumor axis, more recent studies have examined the possibility that bacteria located within tumor cells or within the tumor microenvironment mediate cancer treatment response. Strikingly, this phenomenon has been demonstrated in cancers that arise in anatomic locations that are traditionally thought to be devoid of resident microbiota. In this issue of Cancer Research, Wu and colleagues examine the effects of intratumoral bacterial signatures on treatment response in the setting of neoadjuvant chemotherapy combined with immunotherapy (NACI) in the treatment of esophageal squamous cell carcinoma (ESCC). The study reports that intratumoral Streptococcus, presumably due to bacterial translocation from the gut, predicts the treatment efficacy of NACI in murine models as well as individuals with ESCC. These new findings further highlight the possibility that the presence of intratumoral microbes as well as their associated metabolites influence both the tumor immune microenvironment and immunotherapy efficacy. These findings also raise the intriguing possibility of cross-reactivity between tumor and bacterial antigens. Given that the gut microbiome is potentially a modifiable factor via diet, prebiotics/probiotics, and fecal microbiota transplantation, among other strategies, further exploration into the mechanisms by which gut and/or intratumoral bacteria influence antitumor immunity is certainly warranted. See related article by Wu et al., p. 3131.}, } @article {pmid37712110, year = {2023}, author = {Liao, Y and Peng, Z and Xu, S and Meng, Z and Li, D and Zhou, X and Zhang, R and Shi, S and Hao, L and Liu, L and Yang, W}, title = {Deoxynivalenol Exposure Induced Colon Damage in Mice Independent of the Gut Microbiota.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2300317}, doi = {10.1002/mnfr.202300317}, pmid = {37712110}, issn = {1613-4133}, support = {2022YFC3600600//National Key Research and Development Program of China/ ; NSFC82173521//National Natural Science Foundation of China/ ; 2018YFC1603100//National Natural Science Foundation of China/ ; AT2021-01//Hubei Provincial Key Laboratory for Applied Toxicology/ ; }, abstract = {SCOPE: To investigate whether deoxynivalenol (DON) can induce intestinal damage through gut microbiota in mice.

METHODS AND RESULTS: Mice are orally administered DON (1 mg kg[-1] bw day[-1]) for 4 weeks, and then recipient mice receive fecal microbiota transplantation (FMT) from DON-exposed mice after antibiotic treatment. Furthermore, the mice are orally treated with DON (1 mg kg[-1] bw day[-1]) for 4 weeks after antibiotic treatment. Histological damage, disruption of tight junction protein expression, and increased oxidative stress and apoptosis in the colon as well as higher serum lipopolysaccharides are observed after DON exposure. Moreover, DON exposure changes the composition and diversity of the gut microbiota as well as the contents of fecal metabolites (mainly bile acids). Differential metabolic pathways may be related to mitochondrial metabolism, apoptosis, and inflammation following DON exposure. However, only a decrease in mRNA levels of occludin and claudin-3 is observed in the colon of recipient mice after FMT. After depleting the gut microbiota in mice, DON exposure can also cause histological damage, disorders of tight junction protein expression, and increased oxidative stress and apoptosis in the colon.

CONCLUSIONS: DON exposure can induce colon damage in mice independent of the gut microbiota.}, } @article {pmid37709342, year = {2023}, author = {Fenneman, AC and Rampanelli, E and van der Spek, AH and Fliers, E and Nieuwdorp, M}, title = {Protocol for a double-blinded randomised controlled trial to assess the effect of faecal microbiota transplantations on thyroid reserve in patients with subclinical autoimmune hypothyroidism in the Netherlands: the IMITHOT trial.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e073971}, pmid = {37709342}, issn = {2044-6055}, mesh = {Humans ; Fecal Microbiota Transplantation ; Netherlands ; *Hypothyroidism/therapy ; *Autoimmune Diseases ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Hashimoto's thyroiditis (HT) is a common endocrine autoimmune disease affecting roughly 5% of the general population and involves life-long treatment with levothyroxine, as no curative treatment yet exists. Over the past decade, the crosstalk between gut microbiota and the host immune system has been well-recognised, identifying the gut microbiome as an important factor in host health and disease, including susceptibility to autoimmune diseases. Previous observational studies yielded a link between disruption of the gut microbiome composition and HT. This is the first study that investigates the potential of restoring a disrupted gut microbiome with faecal microbiota transplantations (FMTs) to halt disease progression and dampen autoimmunity.

METHODS AND ANALYSIS: The IMITHOT trial is a randomised, double-blinded, placebo-controlled study evaluating either autologous or allogenic FMTs in medication-naïve patients with subclinical autoimmune hypothyroidism. In total, 34 patients will be enrolled to receive either three allogenic or autologous FMTs. FMT will be made of fresh stool and directly administered into the duodenum. Patients will be evaluated at baseline before the first FMT is administered and at 6, 12 and 24 months post-intervention to assess efficacy and adverse events. The primary outcome measure will be the net incremental increase (incremental area under the curve) on thyrotropin-stimulated free thyroxine and free triiodothyronine release at 6 and 12 months compared with baseline. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient and donor occurred on 18 December 2019.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the hospital Ethics Committee (Medical Ethics Committee) at Amsterdam University Medical Center. The trial's outcomes offer high-quality evidence that aids in unveiling distinct patterns within the gut microbiota potentially associated with improved thyroid function. Consequently, this may open avenues for the future clinical applications of microbial-targeted therapy in individuals at risk of developing overt HT.

TRIAL REGISTRATION NUMBER: NL7931.}, } @article {pmid37709134, year = {2023}, author = {Watanabe, Y and Fujisaka, S and Morinaga, Y and Watanabe, S and Nawaz, A and Hatta, H and Kado, T and Nishimura, A and Bilal, M and Aslam, MR and Honda, K and Nakagawa, Y and Softic, S and Hirabayashi, K and Nakagawa, T and Nagai, Y and Tobe, K}, title = {Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {101797}, doi = {10.1016/j.molmet.2023.101797}, pmid = {37709134}, issn = {2212-8778}, abstract = {OBJECTIVE: Polyphenols have health-promoting effects, such as improving insulin resistance. Isoxanthohumol (IX), a prenylated flavonoid found in beer hops, has been suggested to reduce obesity and insulin resistance; however, the mechanism remains unknown.

METHODS: High-fat diet-fed mice were administered IX. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice.

RESULTS: The administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration increased markers of intestinal barrier function, including thickening the mucin layer and increasing caludin-1, a tight-junction related protein in the colon. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of A. muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis.

CONCLUSIONS: Our study demonstrated that IX prevents obesity and enhances glucose metabolism by inhibiting dietary fat absorption. This mechanism is linked to suppressing pancreatic lipase activity and shifts in microbial composition, notably an increase in A. muciniphila. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.}, } @article {pmid37706187, year = {2023}, author = {Gawey, BJ and Khanna, S}, title = {Clostridioides difficile Infection: Landscape and Microbiome Therapeutics.}, journal = {Gastroenterology & hepatology}, volume = {19}, number = {6}, pages = {319-328}, pmid = {37706187}, issn = {1554-7914}, abstract = {Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and is common in the community. Both younger individuals who may be healthy otherwise and older individuals with comorbid conditions are at risk for developing CDI, with the predominant risk factor being antibiotic use. Unlike other gastrointestinal infections, CDI is not self-limited, requires antimicrobial therapy, and tends to recur at high rates even without additional risk factor exposure. The goals of CDI management include controlling active symptoms and using a recurrence prevention strategy such as a narrow-spectrum antibiotic, tapered and pulsed regimens, antibody- based therapies (directed against toxin B), or microbiome restoration. In recent years, fecal microbiota transplantation (FMT) has been the most used modality to prevent recurrent CDI with high cure rates. Heterogeneity, lack of scalability, and serious adverse events from FMT have led to development of standardized microbiota restoration therapies (MRTs). The US Food and Drug Administration has approved 2 stool-derived MRTs for prevention of recurrent CDI: fecal microbiota, live-jslm, an enema-based therapy; and fecal microbiota spores, live-brpk, an oral therapy. A phase 3 trial for a synthetic oral MRT is underway. This article outlines the pathophysiology and treatment of CDI, focusing primarily on the gut microbiome and standardized MRTs.}, } @article {pmid37704493, year = {2023}, author = {Guillot, N and Roméo, B and Manesh, SS and Milano, G and Brest, P and Zitvogel, L and Hofman, P and Mograbi, B}, title = {Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2023.08.004}, pmid = {37704493}, issn = {1471-499X}, abstract = {The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy.}, } @article {pmid37704113, year = {2023}, author = {Gou, H and Su, H and Liu, D and Wong, CC and Shang, H and Fang, Y and Zeng, X and Chen, H and Li, Y and Huang, Z and Fan, M and Wei, C and Wang, X and Zhang, X and Li, X and Yu, J}, title = {Traditional Medicine Pien Tze Huang Suppresses Colorectal Tumorigenesis through Restoring Gut Microbiota and Metabolites.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.08.052}, pmid = {37704113}, issn = {1528-0012}, abstract = {BACKGROUND AND AIM: Pien-Tze-Huang (PZH) is a well-established Traditional Medicine with beneficial effects against inflammation and cancer. We aim to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota.

METHODS: CRC mouse models were established by azoxymethane plus dextran sulfate sodium (AOM/DSS) treatment or in Apc[min/+] mice, treated with or without PZH (270 and 540mg/kg). Gut barrier function was determined by intestinal permeability assays and transmission electron microscopy (TEM). Fecal microbiota and metabolites were respectively analyzed by metagenomic sequencing and liquid chromatography-mass spectrometry. Germ-free mice or antibiotic-treated mice were used as models of microbiota depletion.

RESULTS: PZH inhibited colorectal tumorigenesis in AOM/DSS treated mice and in Apc[min/+] mice in a dose-dependent manner. PZH treatment altered the gut microbiota profile, with an increased abundance of probiotics Pseudobutyrivibrio xylanivorans and Eubacterium limosum, while pathogenic bacteria Aeromonas veronii, Campylobacter jejuni, Collinsella aerofaciens, and Peptoniphilus harei were depleted. Additionally, PZH increased beneficial metabolites taurine and hypotaurine, bile acids, and unsaturated fatty acids and significantly restored gut barrier function. Transcriptomic profiling revealed that PZH inhibited PI3K-Akt, IL-17, TNF, and Cytokine-Chemokine signaling. Notably, the chemopreventive effect of PZH involved both microbiota-dependent and independent mechanisms. Fecal microbiota transplantation (FMT) from PZH-treated mice to germ-free mice partly recapitulated the chemopreventive effects of PZH. PZH components Ginsenoside-F2 and Ginsenoside-Re demonstrated inhibitory effects on CRC cells and primary organoids, and PZH also inhibited tumorigenesis in AOM/DSS-treated germ-free mice.

CONCLUSION: PZH manipulated gut microbiota and metabolites toward a more favorable profile, improves gut barrier function, and suppresses oncogenic and pro-inflammatory pathways, thereby suppressing colorectal carcinogenesis.}, } @article {pmid37703304, year = {2023}, author = {Subramaniam, S and Fares-Gusmao, R and Sato, S and Cullen, JM and Takeda, K and Farci, P and McGivern, DR}, title = {Distinct disease features of acute and persistent genotype 3 hepatitis E virus infection in immunocompetent and immunosuppressed Mongolian gerbils.}, journal = {PLoS pathogens}, volume = {19}, number = {9}, pages = {e1011664}, doi = {10.1371/journal.ppat.1011664}, pmid = {37703304}, issn = {1553-7374}, abstract = {Hepatitis E virus (HEV) causes self-limited acute hepatitis in immunocompetent individuals and can establish chronic infection in solid organ transplant recipients taking immunosuppressive drugs. A well characterized small animal model is needed to understand HEV pathogenesis. In this study, we established a robust model to study acute and persistent HEV infection using Mongolian gerbils (Meriones unguiculatus) with or without immunosuppression. Gerbils were implanted subcutaneously with continuous release tacrolimus pellet to induce immunosuppression. Gerbils with or without tacrolimus treatment were inoculated with HEV intraperitoneally. Viremia, fecal virus shedding, serum antibody and ALT levels, liver histopathological lesions, hepatocyte apoptosis, and liver macrophage distribution were assessed. Mild to moderate self-limited hepatitis and IgM and IgG antibody responses against HEV ORF2 were observed in immunocompetent gerbils. Levels of HEV-specific IgM responses were higher and lasted longer in immunocompetent gerbils with higher peak viremia. Persistent viremia and fecal virus shedding with either weak, or absent HEV antibody levels were seen in immunosuppressed gerbils. Following HEV infection, serum ALT levels were increased, with lower and delayed peaks observed in immunosuppressed compared to immunocompetent gerbils. In immunocompetent gerbils, foci of apoptotic hepatocytes were detected that were distributed with inflammatory infiltrates containing CD68+ macrophages. However, these foci were absent in immunosuppressed gerbils. The immunosuppressed gerbils showed no inflammation with no increase in CD68+ macrophages despite high virus replication in liver. Our findings suggest adaptive immune responses are necessary for inducing hepatocyte apoptosis, CD68+ macrophage recruitment, and inflammatory cell infiltration in response to HEV infection. Our studies show that Mongolian gerbils provide a promising model to study pathogenesis during acute and persistent HEV infection.}, } @article {pmid37702234, year = {2023}, author = {Sepordeh, S and Jafari, AM and Bazzaz, S and Abbasi, A and Aslani, R and Houshmandi, S and Rad, AH}, title = {Postbiotic as Novel Alternative Agent or Adjuvant for the Common Antibiotic Utilized in the Food Industry.}, journal = {Current pharmaceutical biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1389201025666230912123849}, pmid = {37702234}, issn = {1873-4316}, abstract = {BACKGROUND: Antibiotic resistance is a serious public health problem as it causes previously manageable diseases to become deadly infections that can cause serious disability or even death. Scientists are creating novel approaches and procedures that are essential for the treatment of infections and limiting the improper use of antibiotics in an effort to counter this rising risk.

OBJECTIVE: With a focus on the numerous postbiotic metabolites formed from the beneficial gut microorganisms, their potential antimicrobial actions, and recent associated advancements in the food and medical areas, this review presents an overview of the emerging ways to prevent antibiotic resistance.

RESULTS: Presently, scientific literature confirms that plant-derived antimicrobials, RNA therapy, fecal microbiota transplantation, vaccines, nanoantibiotics, haemofiltration, predatory bacteria, immunotherapeutics, quorum-sensing inhibitors, phage therapies, and probiotics can be considered natural and efficient antibiotic alternative candidates. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. Based on preclinical and clinical studies, postbiotics with their unique characteristics in terms of clinical (safe origin, without the potential spread of antibiotic resistance genes, unique and multiple antimicrobial action mechanisms), technological (stability and feasibility of large-scale production), and economic (low production costs) aspects can be used as a novel alternative agent or adjuvant for the common antibiotics utilized in the production of animal-based foods.

CONCLUSION: Postbiotic constituents may be a new approach for utilization in the pharmaceutical and food sectors for developing therapeutic treatments. Further metabolomics investigations are required to describe novel postbiotics and clinical trials are also required to define the sufficient dose and optimum administration frequency of postbiotics.}, } @article {pmid37701737, year = {2023}, author = {Yuan, Q and Sun, L and Ma, G and Shen, H and Wang, S and Guo, F and Sun, X and Gao, C}, title = {Alterations of the gut microbial community structure modulates the Th17 cells response in a rat model of asphyxial cardiac arrest.}, journal = {Biochemistry and biophysics reports}, volume = {35}, number = {}, pages = {101543}, pmid = {37701737}, issn = {2405-5808}, abstract = {Th17 cells triggered inflammation is a critical element in cerebral ischemic injury, and the gut microbiota intricately impacts T lymphocytes. Nevertheless, it remains unclear whether the gut microbiota involves in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) induced-brain injury through Th17 cells. The present study investigated the interaction between gut microbiota and Th17 cells in a rat model. We observed that CA/CPR induced the alterations of the gut microbial community structure, and elevated the level of IL-17 in the serum, and a slight infiltration of Th17 cells into the brain. The Th17 cells were increased significantly in the peripheral blood, 28.33 ± 6.18% of these Th17 cells were derived from the Peyer's patches of small intestine. Furthermore, fecal microbiota transplantation (FMT) from rats with CA/CPR induced Th17 cell response, promoting hippocampal cell apoptosis and declining learning ability and memory in recipient rats. Taken together, CA/CPR-induced alterations of the gut microbial community structure stimulated Th17 cell response which aggravated brain injury.}, } @article {pmid37699894, year = {2023}, author = {Wortelboer, K and de Jonge, PA and Scheithauer, TPM and Attaye, I and Kemper, EM and Nieuwdorp, M and Herrema, H}, title = {Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5600}, pmid = {37699894}, issn = {2041-1723}, support = {459001008//ZonMw (Netherlands Organisation for Health Research and Development)/ ; 2019.82.004//Diabetes Fonds (Dutch Diabetes Research Foundation)/ ; 17CVD01//Fondation Leducq/ ; 28232//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, abstract = {Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.}, } @article {pmid37698033, year = {2023}, author = {Zuo, T and Liang, G and Huang, Z and Cao, Z and Bai, F and Zhou, Y and Wu, X and Wu, X and Chen, YQ and Balati, M and Maimaitiyiming, M and , and Lan, P}, title = {Baseline gut microbiome features prior to SARS-CoV-2 infection are associated with host symptoms in and post COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29083}, doi = {10.1002/jmv.29083}, pmid = {37698033}, issn = {1096-9071}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; China/epidemiology ; }, abstract = {The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.}, } @article {pmid37697393, year = {2023}, author = {Zeng, X and Li, J and Shan, W and Lai, Z and Zuo, Z}, title = {Gut microbiota of old mice worsens neurological outcome after brain ischemia via increased valeric acid and IL-17 in the blood.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {204}, pmid = {37697393}, issn = {2049-2618}, support = {R01 NS099118/NH/NIH HHS/United States ; }, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; Interleukin-17 ; Fatty Acids, Nonesterified ; *Brain Ischemia ; Inflammation ; }, abstract = {BACKGROUND: Aging is a significant risk factor for ischemic stroke and worsens its outcome. However, the mechanisms for this worsened neurological outcome with aging are not clearly defined.

RESULTS: Old C57BL/6J male mice (18 to 20 months old) had a poorer neurological outcome and more severe inflammation after transient focal brain ischemia than 8-week-old C57BL/6J male mice (young mice). Young mice with transplantation of old mouse gut microbiota had a worse neurological outcome, poorer survival curve, and more severe inflammation than young mice receiving young mouse gut microbiota transplantation. Old mice and young mice transplanted with old mouse gut microbiota had an increased level of blood valeric acid. Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia. The increase of interleukin-17 caused by valeric acid was inhibited by a free fatty acid receptor 2 antagonist. Neutralizing interleukin-17 in the blood by its antibody improved neurological outcome and attenuated inflammatory response in mice with brain ischemia and receiving valeric acid. Old mice transplanted with young mouse feces had less body weight loss and better survival curve after brain ischemia than old mice transplanted with old mouse feces or old mice without fecal transplantation.

CONCLUSIONS: These results suggest that the gut microbiota-valeric acid-interleukin-17 pathway contributes to the aging-related changes in the outcome after focal brain ischemia and response to stimulus. Valeric acid may activate free fatty acid receptor 2 to increase interleukin-17.}, } @article {pmid37696680, year = {2023}, author = {Del Chierico, F and Cardile, S and Baldelli, V and Alterio, T and Reddel, S and Bramuzzo, M and Knafelz, D and Lega, S and Bracci, F and Torre, G and Maggiore, G and Putignani, L}, title = {Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izad203}, pmid = {37696680}, issn = {1536-4844}, support = {//Italian Ministry of Health/ ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.

METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).

RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.

CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.}, } @article {pmid37696191, year = {2023}, author = {Gao, T and Zhang, H and Li, Q and Zhao, F and Wang, N and He, W and Zhang, J and Wang, R}, title = {Fuzi decoction treats chronic heart failure by regulating the gut microbiota, increasing the short-chain fatty acid levels and improving metabolic disorders.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {236}, number = {}, pages = {115693}, doi = {10.1016/j.jpba.2023.115693}, pmid = {37696191}, issn = {1873-264X}, abstract = {Fuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC-MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota. Our results identified 27 in FD-containing serum. FZD increased the Firmicutes-to-Bacteroidetes ratio and the Lactobacillus abundance and affected the β diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine, leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid, butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.}, } @article {pmid37548627, year = {2023}, author = {Ramos Maia, DR and Otsuki, DA and Rodrigues, CE and Zboril, S and Sanches, TR and Neto, AND and Andrade, L and Auler, JOC}, title = {TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {3}, pages = {469-477}, doi = {10.1097/SHK.0000000000002191}, pmid = {37548627}, issn = {1540-0514}, mesh = {Humans ; *Acute Kidney Injury/therapy/chemically induced ; Endothelial Cells/metabolism ; Kidney/metabolism ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells/metabolism ; NF-kappa B/metabolism ; *Sepsis/complications/therapy/metabolism ; Toll-Like Receptor 4/metabolism ; Umbilical Cord/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Animals ; Swine ; }, abstract = {Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.}, } @article {pmid37694136, year = {2023}, author = {Bubeck, AM and Urbain, P and Horn, C and Jung, AS and Ferrari, L and Ruple, HK and Podlesny, D and Zorn, S and Laupsa-Borge, J and Jensen, C and Lindseth, I and Lied, GA and Dierkes, J and Mellgren, G and Bertz, H and Matysik, S and Krautbauer, S and Liebisch, G and Schoett, HF and Dankel, SN and Fricke, WF}, title = {High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels.}, journal = {iScience}, volume = {26}, number = {9}, pages = {107697}, pmid = {37694136}, issn = {2589-0042}, abstract = {Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.}, } @article {pmid37692169, year = {2023}, author = {Negi, S and Pahari, S}, title = {Editorial: Gut microbiota as a weapon against infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1277517}, doi = {10.3389/fcimb.2023.1277517}, pmid = {37692169}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; }, } @article {pmid37691890, year = {2023}, author = {Wang, B and Hu, W and Zhang, X and Cao, Y and Shao, L and Xu, X and Liu, P}, title = {Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {35}, number = {4}, pages = {386-398}, doi = {10.21147/j.issn.1000-9604.2023.04.05}, pmid = {37691890}, issn = {1000-9604}, abstract = {OBJECTIVE: The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT).

METHODS: A total of 108 patients with various hematological disorders were selected from Peking University People's Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.

RESULTS: After HSCT, significant decreases in calf circumference and body mass index (BMI) were observed, accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT (P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients (P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the post-HSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre- and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size (LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups (P<0.05).

CONCLUSIONS: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.}, } @article {pmid37691753, year = {2023}, author = {Malik, A and Malik, MI}, title = {Fecal Microbiota Transplantation in Human Immunodeficiency Virus-Infected Patient Population: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research}, volume = {16}, number = {4}, pages = {209-216}, doi = {10.14740/gr1624}, pmid = {37691753}, issn = {1918-2805}, abstract = {BACKGROUND: Patients with human immunodeficiency virus (HIV) infection suffer from alterations in gut microbiota due to recurrent gastrointestinal infections and systemic inflammation. Fecal microbiota transplantation (FMT) appears to be a potential therapy; however, there are concerns about its safety. Likewise, no previous meta-analysis evaluated FMT efficacy in HIV-infected patients.

METHODS: We conducted a thorough electronic search on PubMed, Scopus, OVID, Web of Science, and Cochrane CENTRAL for clinical studies assessing the safety and efficacy of FMT in patients with HIV and gastrointestinal dysbiosis, where FMT was indicated to restore the disrupted microbiota.

RESULTS: FMT significantly restored the typical microbiome in patients with Clostridium difficile (C. difficile) and non-C. difficile and reduced the risk of gastrointestinal infections in HIV patients receiving antiretroviral therapy (odds ratio (OR) = 0.774, 95% confidence interval (CI): (0.62, 0.966)). Furthermore, adverse events, such as distention and bloating, associated with FMT were comparable between HIV and health controls (OR = 0.60, 95% CI: (0.07, 4.6)), with no statistical difference.

CONCLUSIONS: Current evidence demonstrated that FMT is safe and effective in HIV patients suffering from alterations in gut microbiota. We recommend further multi-centric clinical studies to address the optimal transplant amount and source for FMT. To the best of our knowledge, this is the first meta-analysis to assess the safety and efficacy of FMT in patients with HIV.}, } @article {pmid37690971, year = {2023}, author = {Liu, X and Liu, M and Zhao, M and Li, P and Gao, C and Fan, X and Cai, G and Lu, Q and Chen, X}, title = {Fecal microbiota transplantation for the management of autoimmune diseases: Potential mechanisms and challenges.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {103109}, doi = {10.1016/j.jaut.2023.103109}, pmid = {37690971}, issn = {1095-9157}, abstract = {Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.}, } @article {pmid37690584, year = {2023}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {110861}, doi = {10.1016/j.pnpbp.2023.110861}, pmid = {37690584}, issn = {1878-4216}, abstract = {There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders like anxiety, depression, and cognitive dysfunctions. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by both the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.}, } @article {pmid37689184, year = {2023}, author = {Liu, J and Peng, F and Cheng, H and Zhang, D and Zhang, Y and Wang, L and Tang, F and Wang, J and Wan, Y and Wu, J and Zhou, Y and Feng, W and Peng, C}, title = {Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {166837}, doi = {10.1016/j.scitotenv.2023.166837}, pmid = {37689184}, issn = {1879-1026}, abstract = {The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.}, } @article {pmid37686740, year = {2023}, author = {Chen, J and Deng, LL and Xiao, XL and Long, SY and Deng, Y and Peng, T and Xie, J and Zhang, XY}, title = {An Association between Decreased Small Intestinal RNA Modification and Disturbed Glucagon-like Peptide-1 Secretion under High-Fat Diet Stress.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686740}, issn = {2072-6643}, support = {23SYSX0098//Project of Science and Technology Ministry of Sichuan Province/ ; 32001078//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Diet, High-Fat/adverse effects ; Glucagon-Like Peptide 1 ; Mice, Obese ; *Gastrointestinal Hormones ; Intestine, Small ; }, abstract = {Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.}, } @article {pmid37686143, year = {2023}, author = {Campagnoli, LIM and Varesi, A and Barbieri, A and Marchesi, N and Pascale, A}, title = {Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686143}, issn = {1422-0067}, mesh = {Humans ; Eye ; Face ; *Glaucoma ; *Macular Degeneration ; *Diabetic Retinopathy ; }, abstract = {The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.}, } @article {pmid37686104, year = {2023}, author = {Uceda, S and Echeverry-Alzate, V and Reiriz-Rojas, M and Martínez-Miguel, E and Pérez-Curiel, A and Gómez-Senent, S and Beltrán-Velasco, AI}, title = {Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, doi = {10.3390/ijms241713294}, pmid = {37686104}, issn = {1422-0067}, abstract = {The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.}, } @article {pmid37681235, year = {2023}, author = {Wu, X and Ai, R and Xu, J and Wen, Q and Pan, H and Zhang, Z and Wang, N and Fang, Y and Ding, D and Wang, Q and Han, S and Liu, X and Wu, M and Jia, Z and Song, J and Lin, T and Cui, B and Nie, Y and Wang, X and Zhang, F}, title = {Washed microbiota transplantation for Clostridioides difficile infection: a national multi-center real-world study.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.13227}, pmid = {37681235}, issn = {1751-2980}, abstract = {BACKGROUND & AIM: Fecal microbiota transplantation (FMT) has been recommended for treating recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings.

METHODS: This real-world cohort study included CDI patients from multiple centers who underwent WMT. The primary outcome was the clinical cure rate of CDI within 8-week post-WMT. Secondary outcomes included the reduction in total abdominal symptom score (TASS), CDI recurrence rate, and safety during follow-up period.

RESULTS: Overall, 90.7% (49/54) of patients achieved clinical cure within 8-week post-WMT. The cure rate for severe and complicated CDI (ScCDI) (n = 30) was 83.3%, and it reached 100% for non-ScCDI (n = 24, p = 0.059). No difference was observed in the clinical cure rate between patients with primary CDI and recurrent CDI (91.89% vs. 88.23%, p = 0.645). One-week post-WMT, the TASS showed a remarkable decrease compared to that before WMT (p < 0.001). 8.16% of patients (4/49) suffered CDI recurrence during follow-up. A WHO performance score of 4, age ≥ 65, higher TASS score, and higher Charlson comorbidity index score (p = 0.018, 0.03, 0.01, 0.034, respectively) were potential risk factors for efficacy. Four transient adverse events related to WMT (3.8%, 4/105) were observed.

CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT might be a recommendation for CDI, especially for those in serious condition or with complex comorbidities for decreasing deterioration, medical costs, and pain. This article is protected by copyright. All rights reserved.}, } @article {pmid37679804, year = {2023}, author = {Zhang, Z and Ye, J and Liu, X and Zhao, W and Zhao, B and Gao, X and Lan, H and Wu, Y and Yang, Y and Cao, P}, title = {Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {114}, pmid = {37679804}, issn = {1749-8546}, support = {BRA202202//The 333 high-level talents project of Jiangsu Province/ ; }, abstract = {BACKGROUND: Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.

METHODS: In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis.

RESULTS: HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.

CONCLUSIONS: HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.}, } @article {pmid37679072, year = {2023}, author = {Zhou, Z and Zhang, Y and Liu, M and Jia, W and Cheng, R and Shen, X and He, F}, title = {[Influence of different fecal microbiota transplantation cycles on the recovery of intestinal microbiota in the antibiotic cocktail-pretreated mice].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {52}, number = {4}, pages = {585-590}, doi = {10.19813/j.cnki.weishengyanjiu.2023.04.011}, pmid = {37679072}, issn = {1000-8020}, abstract = {OBJECTIVE: To explore the effects of different transplantation frequencies and time of fecal microbiota transplantation on mice.

METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, fecal microbiota transplantation group 1(FMT1), fecal microbiota transplantation group 2(FMT2), and fecal microbiota transplantation group 3(FMT3). The control group was used as the donor of fecal microbiota transplantation, and the FMT1, FMT2, and FMT3 groups were intervened with mixed antibiotics(200 μL/d) for 2 weeks, and received fecal bacterial suspension(200 μL/d). The transplantation time of the FMT1 group frequency was 1 time/d for 1 weeks, the FMT2 group was 1 time/d for 2 weeks, and the FMT3 group was 3 times/week for 2 weeks. At the end of the experiment, the feces of the mice were collected to analyze the gut microbiota.

RESULTS: Compared with the control group, there were more independent Amplicon Sequence Variants in the intestinal microbiota of mice in FMT1 group, FMT2 group and FMT3 group, and the ACE index and Chao1 index were significantly reduced(P<0.05). Beta diversity showed differences between fecal microbiota transplantation and control groups, with FMT2 and control groups being the closest. At the phylum level, there were two species in FMT1 group and one species in FMT3 group showed statistically significant differences compared with control group(P<0.05). However, there was no significant difference between the FMT2 group and the control group. At the genus level, there were 6 species in the FMT1 with statistically significant differences from the control group(P<0.05), and 2 species in the FMT2, 5 species in the FMT3 respectively. Among which FMT2 group has the least number of species that differed from the control group, suggesting that the compitsition of its intestinal microbiota is closet to that of the control group.

CONCLUSION: Fecal bacteria transplantation helps to restore the intestinal microbiota structure of mice cleaned by antibiotics, and different transplantation frequencies and transplantation times have different recovery effects on the intestinal microbiota of mice pretreated with antibiotics, and the fecal bacteria transplantation effect is better with 1 time/d lasting 2 weeks.}, } @article {pmid37678703, year = {2023}, author = {Meng, Y and Sun, J and Zhang, G}, title = {Pick fecal microbiota transplantation to enhance therapy for major depressive disorder.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {110860}, doi = {10.1016/j.pnpbp.2023.110860}, pmid = {37678703}, issn = {1878-4216}, abstract = {In recent years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for major depressive disorder (MDD). The goal of the operation is to restore a healthy gut microbiota by introducing feces from a healthy donor into the recipient's digestive system. The brain-gut axis is thought to have a significant role in regulating mood, behavior, and cognition, which supports the use of FMT in the treatment of MDD. Numerous studies have shown a correlation between abnormalities of the gut microbiota and MDD, whereas FMT has demonstrated the potential to restore microbial equilibrium. While FMT has shown encouraging results, it is crucial to highlight the potential hazards and limits inherent to this therapeutic approach. Stool donor-to-recipient disease transfer is a concern of FMT. Furthermore, it still needs to be determined what effect FMT has on the gut microbiota and the brain in the long run. This literature review provides an overview of the possible efficacy of FMT as a therapeutic modality for MDD. There is hope for patients who have not reacted well to typical antidepressant therapy since FMT may become an invaluable tool in the treatment of MDD as researchers continue to examine the relationship between gut microbiota and MDD.}, } @article {pmid37678377, year = {2023}, author = {Baker, KA and Poole, C}, title = {Current and Emerging Applications of Fecal Microbiota Transplantation.}, journal = {The American journal of nursing}, volume = {Published Ahead of Print}, number = {}, pages = {}, doi = {10.1097/01.NAJ.0000978920.88346.77}, pmid = {37678377}, issn = {1538-7488}, abstract = {Fecal microbiota transplantation (FMT) is a life-changing treatment for people with recurrent Clostridioides difficile infection (rCDI). Frequently acquired in the hospital, CDI can cause serious gastrointestinal symptoms, including persistent watery diarrhea, abdominal pain, and severe dehydration. Antibiotics, the primary treatment, can unfortunately disrupt the gut microbiome and lead to antimicrobial resistance. FMT involves introducing stool from a healthy donor into the affected recipient to strengthen their compromised microbiome. Individuals receiving this treatment have reported remarkable improvement in clinical outcomes and quality of life. In addition to a discussion of rCDI within the context of the gastrointestinal microbiome, this article provides an overview of the FMT procedure, discusses nursing management of individuals undergoing FMT, and highlights emerging applications beyond rCDI. A case scenario is also provided to illustrate a typical trajectory for a patient undergoing FMT.}, } @article {pmid37678055, year = {2023}, author = {Gao, T and Li, Y and Wang, X and Tao, R and Ren, F}, title = {Bifidobacterium longum 68S mediated gut-skin axis homeostasis improved skin barrier damage in aging mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {120}, number = {}, pages = {155051}, doi = {10.1016/j.phymed.2023.155051}, pmid = {37678055}, issn = {1618-095X}, abstract = {BACKGROUND: Bifidobacterium as probiotics, play important roles in skin status, while the potential mechanisms interaction remains unknown. The study further explored the potential mechanism of B. longum 68S in ameliorating skin barrier damage from the perspective of the gut-skin axis in aging mice.

METHODS: B. longum 68S supplied natural aging mouse model and fecal microbiota transplantation (FMT) experiment proves the key role of intestinal microbiota in B. longum 68S up-regulating the production of ceramide synthesis key enzyme (SPT1) and ceramide level and improving skin barrier damage. Moreover, B. longum 68S supplied SPT1 gene deletion mouse model to investigate the mechanism of B. longum 68S on improving skin barrier damage.

RESULTS: Transcriptome analysis and 16S rRNA high-throughput pyrosequencing demonstrated that aging mice exhibited skin barrier dysfunction and intestinal dysbiosis. Meanwhile, aging mice exhibited an up-regulation in the trans epidermal water loss (TEWL) and a down-regulation in the level of SPT1, ceramide and skin barrier-related proteins (Loricrin, Keratin 10 and Desmoglein 1). Similarity, the FMT from aging mice to normal mice and SPT1 gene deletion mice could rebuild skin barrier damage and B. longum 68S supplementation exerted a positive effect on it. Further, B. longum 68S-mediated SPT1-derived ceramide production prevented impaired ceramide synthesis-induced endoplasmic reticulum stress and apoptotic response, ultimately improving skin barrier damage in vitro.

CONCLUSION: Emerging anti-aging therapies are necessary given the poor safety profiles of current pharmaceutical drugs. B. longum 68S may be better alternatives, considering the association between the gut microbiota and healthy aging. The findings suggested that B. longum 68S-mediated gut-skin axis homeostasis, thereby exhibiting an anti-aging effect and facilitate a better understanding of the mechanisms governing the various beneficial effects of B. longum 68S.}, } @article {pmid37677965, year = {2023}, author = {Wang, J and Guo, X and Zou, Z and Yu, M and Li, X and Xu, H and Chen, Y and Jiao, T and Wang, K and Ma, Y and Jiang, J and Liang, X and Wang, J and Xie, C and Zhong, Y}, title = {Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {166}, number = {}, pages = {115434}, doi = {10.1016/j.biopha.2023.115434}, pmid = {37677965}, issn = {1950-6007}, abstract = {Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.}, } @article {pmid37676478, year = {2023}, author = {Wang, G and Jiang, Z and Song, Y and Xing, Y and He, S and Boomi, P}, title = {Gut microbiota contribution to selenium deficiency-induced gut-liver inflammation.}, journal = {BioFactors (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1002/biof.2006}, pmid = {37676478}, issn = {1872-8081}, support = {222102110290//Key R&D and Promotion Projects in Henan Province/ ; 222102110381//Key R&D and Promotion Projects in Henan Province/ ; 32102744//National Natural Science Foundation of China/ ; 202300410008//Natural Science Foundation of Henan Province/ ; }, abstract = {There is limited knowledge about the factors that drive gut-liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.}, } @article {pmid37675433, year = {2023}, author = {Wei, J and Chen, J and Fang, X and Liu, T and Yuan, Y and Zhang, J}, title = {Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1236904}, pmid = {37675433}, issn = {1664-302X}, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.

METHODS: This clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3-9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children's Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants' legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200058459.}, } @article {pmid37675126, year = {2023}, author = {Shan, H and Wei, C and Zhang, J and He, M and Zhang, Z}, title = {Case Report: Severe Diarrhea Caused by Cryptosporidium Diagnosed by Metagenome Next-Generation Sequencing in Blood.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {5777-5782}, pmid = {37675126}, issn = {1178-6973}, abstract = {BACKGROUND: Cryptosporidium is one of the major pathogens causing diarrhea worldwide. At present, cryptosporidiosis is difficult to prevent and control, especially in immunocompromised hosts. It may cause life-threatening diarrhea and malabsorption among children and immunocompromised patients. Therefore, it is very important to explore rapid diagnostic tools and treatment methods for Cryptosporidium infection.

CASE PRESENTATION: We reported a case of severe diarrhea caused by cryptosporidiosis in a liver transplant recipient, whose condition was finally confirmed by metagenomic next-generation sequencing (mNGS) and fecal microscopy. His illness was resolved with immunosuppression regulation, nitazoxanide administration, and infection control.

CONCLUSION: So far, nitazoxanide is still the first choice for the treatment of cryptosporidiosis. Our institutional experience suggested that nitazoxanide alone may be effective on the basis of adjusting immunosuppressant. In addition, even though diagnosis of Cryptosporidium infection is a challenge, mNGS can serve as a rapid screening tool in low-prevalence setting.}, } @article {pmid37674043, year = {2023}, author = {Ma, XZ and Chen, LL and Qu, L and Li, H and Wang, J and Song, N and Xie, JX}, title = {Gut microbiota-induced CXCL1 elevation triggers early neuroinflammation in the substantia nigra of Parkinsonian mice.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {37674043}, issn = {1745-7254}, abstract = {Gut microbiota disturbance and systemic inflammation have been implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD). How the alteration of gut microbiota results in neuropathological events in PD remains elusive. In this study, we explored whether and how environmental insults caused early neuropathological events in the substantia nigra (SN) of a PD mouse model. Aged (12-month-old) mice were orally administered rotenone (6.25 mg·kg[-1]·d[-1]) 5 days per week for 2 months. We demonstrated that oral administration of rotenone to ageing mice was sufficient to establish a PD mouse model and that microglial activation and iron deposition selectively appeared in the SN of the mice prior to loss of motor coordination and dopaminergic neurons, and these events could be fully blocked by microglial elimination with a PLX5622-formulated diet. 16 S rDNA sequencing analysis showed that the gut microbiota in rotenone-treated mice was altered, and mice receiving faecal microbial transplantation (FMT) from ageing mice treated with rotenone for 2 months exhibited the same pathology in the SN. We demonstrated that C-X-C motif chemokine ligand-1 (CXCL1) was an essential molecule, as intravenous injection of CXCL1 mimicked almost all the pathology in serum and SN induced by oral rotenone and FMT. Using metabolomics and transcriptomics analyses, we identified the PPAR pathway as a key pathway involved in rotenone-induced neuronal damage. Inhibition of the PPARγ pathway was consistent in the above models, whereas its activation by linoleic acid (60 mg·kg[-1]·d[-1], i.g. for 1 week) could block these pathological events in mice intravenously injected with CXCL1. Altogether, these results reveal that the altered gut microbiota resulted in neuroinflammation and iron deposition occurring early in the SN of ageing mice with oral administration of rotenone, much earlier than motor symptoms and dopaminergic neuron loss. We found that CXCL1 plays a crucial role in this process, possibly via PPARγ signalling inhibition. This study may pave the way for understanding the "brain-gut-microbiota" molecular regulatory networks in PD pathogenesis. The aged C57BL/6 male mice with rotenone intragastric administration showed altered gut microbiota, which caused systemic inflammation, PPARγ signalling inhibition and neuroinflammation, brain iron deposition and ferroptosis, and eventually dopaminergic neurodegeneration in PD.}, } @article {pmid37673907, year = {2023}, author = {Xia, Y and Xiao, Y and Wang, ZH and Liu, X and Alam, AM and Haran, JP and McCormick, BA and Shu, X and Wang, X and Ye, K}, title = {Bacteroides Fragilis in the gut microbiomes of Alzheimer's disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5471}, pmid = {37673907}, issn = {2041-1723}, support = {AG065177//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 2022CFA104//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; }, abstract = {Gut dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPβ transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPβ transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPβ/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors' fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing analysis shows higher abundance of proinflammatory Bacteroides fragilis in AD-FMT mice. Active components characterization from the sera and brains of the transplanted mice revealed that both 12-HHTrE and PGE2 activate primary microglia, fitting with poly-unsaturated fatty acid (PUFA) metabolites enrichment identified by metabolomics. Strikingly, recolonization with live but not dead Bacteroides fragilis elicited AD pathologies in Thy1-C/EBPβ transgenic mice, so did 12-HHTrE or PGE2 treatment alone. Collectively, our findings support a causal role for Bacteroides fragilis and the PUFA metabolites in activating microglia and inducing AD pathologies in Thy1- C/EBPβ transgenic mice.}, } @article {pmid37673036, year = {2023}, author = {Ni, Y and Qian, L and Siliceo, SL and Long, X and Nychas, E and Liu, Y and Ismaiah, MJ and Leung, H and Zhang, L and Gao, Q and Wu, Q and Zhang, Y and Jia, X and Liu, S and Yuan, R and Zhou, L and Wang, X and Li, Q and Zhao, Y and El-Nezami, H and Xu, A and Xu, G and Li, H and Panagiotou, G and Jia, W}, title = {Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations.}, journal = {Cell metabolism}, volume = {35}, number = {9}, pages = {1530-1547.e8}, doi = {10.1016/j.cmet.2023.08.002}, pmid = {37673036}, issn = {1932-7420}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.08% absolute reduction of intrahepatic triglyceride content (IHTC), which was 5.89% after adjusting for weight loss. Serum branched-chain amino acids (BCAAs) and gut microbial species, in particular Bacteroides stercoris, significantly correlated with IHTC and liver enzymes and were reduced by RS. Multi-omics integrative analyses revealed the interplay among gut microbiota changes, BCAA availability, and hepatic steatosis, with causality supported by fecal microbiota transplantation and monocolonization in mice. Thus, RS dietary supplementation might be a strategy for managing NAFLD by altering gut microbiota composition and functionality.}, } @article {pmid37672855, year = {2023}, author = {Xia, X and Zhang, Y and Zhu, L and Ying, Y and Hao, W and Wang, L and He, L and Zhao, D and Chen, JX and Gao, Y and Huang, JQ}, title = {Liquiritin apioside alleviates colonic inflammation and accompanying depression-like symptoms in colitis by gut metabolites and the balance of Th17/Treg.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {120}, number = {}, pages = {155039}, doi = {10.1016/j.phymed.2023.155039}, pmid = {37672855}, issn = {1618-095X}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied.

PURPOSE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice.

METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry.

RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites.

CONCLUSION: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.}, } @article {pmid37671830, year = {2023}, author = {Xia, K and Gao, R and Li, L and Wu, X and Wu, T and Ruan, Y and Yin, L and Chen, C}, title = {Transformation of colitis and colorectal cancer: a tale of gut microbiota.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/1040841X.2023.2254388}, pmid = {37671830}, issn = {1549-7828}, abstract = {Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.}, } @article {pmid37671803, year = {2023}, author = {Li, N and Tan, S and Wang, Y and Deng, J and Wang, N and Zhu, S and Tian, W and Xu, J and Wang, Q}, title = {Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2252764}, doi = {10.1080/19490976.2023.2252764}, pmid = {37671803}, issn = {1949-0984}, abstract = {The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.}, } @article {pmid37668964, year = {2023}, author = {Zhang, Y and Liu, J and Liu, X and Zhou, Y and Geng, J and Shi, Z and Ma, L}, title = {Fecal Microbiota Transplantation-Mediated Ghrelin Restoration Improves Neurological Functions After Traumatic Brain Injury: Evidence from 16S rRNA Sequencing and In Vivo Studies.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37668964}, issn = {1559-1182}, abstract = {This study aimed to investigate how gut microbiota dysbiosis impacts the repair of the blood-brain barrier and neurological deficits following traumatic brain injury (TBI). Through 16S rRNA sequencing analysis, we compared the gut microbiota of TBI rats and normal controls, discovering significant differences in abundance, species composition, and ecological function, potentially linked to Ghrelin-mediated brain-gut axis functionality. Further, in vivo experiments showed that fecal microbiota transplantation or Ghrelin injection could block the intracerebral TNF signaling pathway, enhance GLP-1 expression, significantly reduce brain edema post-TBI, promote the repair of the blood-brain barrier, and improve neurological deficits. However, the TNF signaling pathway activation could reverse these beneficial effects. In summary, our research suggests that by restoring the balance of gut microbiota, the levels of Ghrelin can be elevated, leading to the blockade of intracerebral TNF signaling pathway and enhanced GLP-1 expression, thereby mitigating post-TBI blood-brain barrier disruption and neurological injuries.}, } @article {pmid37668317, year = {2023}, author = {Mendes de Almeida, V and Engel, DF and Ricci, MF and Cruz, CS and Lopes, ÍS and Alves, DA and d' Auriol, M and Magalhães, J and Machado, EC and Rocha, VM and Carvalho, TG and Lacerda, LSB and Pimenta, JC and Aganetti, M and Zuccoli, GS and Smith, BJ and Carregari, VC and da Silva Rosa, E and Galvão, I and Dantas Cassali, G and Garcia, CC and Teixeira, MM and André, LC and Ribeiro, FM and Martins, FS and Saia, RS and Costa, VV and Martins-de-Souza, D and Hansbro, PM and Marques, JT and Aguiar, ERGR and Vieira, AT}, title = {Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2249146}, doi = {10.1080/19490976.2023.2249146}, pmid = {37668317}, issn = {1949-0984}, mesh = {Animals ; Mice ; *COVID-19 ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Anti-Bacterial Agents ; Disease Progression ; }, abstract = {Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.}, } @article {pmid37667968, year = {2023}, author = {Yau, YK and Su, Q and Xu, Z and Tang, W and Ching, JYL and Mak, JWY and Cheung, CP and Fung, M and Ip, M and Chan, PKS and Wu, JCY and Chan, FKL and Ng, SC}, title = {Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.17703}, pmid = {37667968}, issn = {1365-2036}, support = {//Health and Medical Research Fund, the Food and Health Bureau/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS).

AIM: We performed a randomised trial to assess the efficacy of FMT in patients with IBS.

METHODS: We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT.

RESULTS: At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT.

CONCLUSION: FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).}, } @article {pmid37667688, year = {2023}, author = {Feuerstadt, P and Oneto, C and Tillotson, G and Van Hise, NW}, title = {Patient Perception of Route of Rectal Administration of Live Biotherapeutic Product for Recurrent Clostridioides difficile Infection.}, journal = {Patient preference and adherence}, volume = {17}, number = {}, pages = {2153-2159}, pmid = {37667688}, issn = {1177-889X}, abstract = {INTRODUCTION: CDI is a recurrent disease that is treated with antibiotics, but patients commonly experience repeat infections with significant impacts on hospital budgets and patient health quality. Standard of care management includes the antibiotics, vancomycin and fidaxomicin, which frequently provide clinical response, but do not avoid recurrence of Clostridioides difficile infection (rCDI). These recurrent infections occur due to dysbiosis of the colonic microbiota. One adjunctive therapeutic approach is to restore the deficient gastrointestinal flora using fecal microbiota transplantation (FMT) or live biotherapeutic products (LBP) when given after standard of care antimicrobials, which have been successful in reducing repeat infections with success rates up to 88%. FMT or LBP can be given by various routes.

METHODS: Two groups of subjects aged ≥18 years with at least one previous CDI episode within the previous 36 months completed self-administered online surveys to assess the acceptability of an LBP administered rectally. Group 1 consisted of LBP-recipients who had received RBL (REBYOTA) rectally as part of the Phase III PUNCH CD3 clinical trial. Group 2 consisted of LBP-naïve subjects who volunteered to participate and had experienced CDI within the prior 36 months but had no history of receiving FMT or LBP therapy.

RESULTS: LBP-recipients considered rectal administration easy (96%) and quick (94%), while 98% of respondents considered the lack of need for bowel preparation appealing. Most LBP-recipients (96%) wished they had earlier access to RBL. Most LBP-naïve subjects (87%) were likely or somewhat likely to consider a rectally administered treatment and 80% preferred a treatment option that does not require bowel preparation. Many of these subjects (76%) expressed interest in finding out about new treatment options for rCDI.

DISCUSSION: LBP-recipients and LBP-naïve subjects alike felt that rectal delivery of microbiome therapy is not only acceptable but highly interesting as a treatment avenue.}, } @article {pmid37667277, year = {2023}, author = {Hotta, R and Rahman, A and Bhave, S and Stavely, R and Pan, W and Srinivasan, S and de Couto, G and Rodriguez-Borlado, L and Myers, R and Burns, AJ and Goldstein, AM}, title = {Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.}, journal = {Stem cell research & therapy}, volume = {14}, number = {1}, pages = {232}, pmid = {37667277}, issn = {1757-6512}, mesh = {Animals ; Mice ; *Neurons ; *Muscle, Smooth ; Cell- and Tissue-Based Therapy ; Colon ; Electric Stimulation ; }, abstract = {BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function.

METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS[-/-] mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1-2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility.

RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS[-/-] recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS.

CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.}, } @article {pmid37665106, year = {2023}, author = {}, title = {Retraction statement: Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats.}, journal = {Acta physiologica (Oxford, England)}, volume = {}, number = {}, pages = {e14039}, doi = {10.1111/apha.14039}, pmid = {37665106}, issn = {1748-1716}, abstract = {Toral, M, Robles-Vera, I, de la Visitación, N, et al. Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats. Acta Physiol. 2019; 227:e13285. https://doi.org/10.1111/apha.13285. The above article, published online on April 20, 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Pontus B. Persson, the Scandinavian Physiological Society, and John Wiley and Sons Ltd. The retraction has been agreed due to the similarity of a figure and inconsistencies regarding underlying data between this article and the following article published in Front Physiol, "Critical Role of the Interaction Gut Microbiota-Sympathetic Nervous System in the Regulation of Blood Pressure" by Toral M, Robles-Vera I, de la Visitación N, et al., 2019; 10:231. doi: 10.3389/fphys.2019.00231.}, } @article {pmid37665061, year = {2023}, author = {Yang, J and Shi, X and Gao, R and Fan, L and Chen, R and Cao, Y and Xu, T and Yang, J}, title = {Polydatin alleviates bleomycin-induced pulmonary fibrosis and alters the gut microbiota in a mouse model.}, journal = {Journal of cellular and molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcmm.17937}, pmid = {37665061}, issn = {1582-4934}, support = {81774231//Data Center of Management Science, National Natural Science Foundation of China - Peking University/ ; 82174300//Data Center of Management Science, National Natural Science Foundation of China - Peking University/ ; }, abstract = {To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, β-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.}, } @article {pmid37663603, year = {2023}, author = {Hu, C and He, T and Zou, B and Li, H and Zhao, J and Hu, C and Cui, J and Huang, Z and Shu, S and Hao, Y}, title = {Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions-a case report.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1219104}, pmid = {37663603}, issn = {1664-0640}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient's symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms.}, } @article {pmid37662996, year = {2023}, author = {Hsieh, JC and Chuang, ST and Hsu, YT and Ho, ST and Li, KY and Chou, SH and Chen, MJ}, title = {In vitro ruminal fermentation and cow-to-mouse fecal transplantations verify the inter-relationship of microbiome and metabolome biomarkers: potential to promote health in dairy cows.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1228086}, pmid = {37662996}, issn = {2297-1769}, abstract = {INTRODUCTION: There are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated.

OBJECTIVE: In the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows.

METHODS: We analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT).

RESULTS: Two species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman's correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces.

DISCUSSION: We provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.}, } @article {pmid37662857, year = {2023}, author = {Wen, X and Xie, R and Wang, HG and Zhang, MN and He, L and Zhang, MH and Yang, XZ}, title = {Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway.}, journal = {World journal of gastroenterology}, volume = {29}, number = {30}, pages = {4657-4670}, pmid = {37662857}, issn = {2219-2840}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC.

AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice.

METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing.

RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm[3], Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01).

CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.}, } @article {pmid37661203, year = {2023}, author = {Feng, J and Chen, Y and Liu, Y and Lin, L and Lin, X and Gong, W and Xia, R and He, J and Sheng, J and Cai, H and Xiao, C}, title = {Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14494}, pmid = {37661203}, issn = {2045-2322}, abstract = {To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.}, } @article {pmid37661007, year = {2023}, author = {McGuinness, AJ and Loughman, A and Foster, JA and Jacka, F}, title = {Mood disorders: the gut bacteriome and beyond.}, journal = {Biological psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biopsych.2023.08.020}, pmid = {37661007}, issn = {1873-2402}, abstract = {Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely influences, the pathogenesis of mental disorders, including major depressive disorder and bipolar disorder. However, whilst substantial advances in the field of microbiome science have been made, we have likely only scratched the surface in our understanding of how these ecosystems might contribute to mental disorder pathophysiology. Beyond the gut bacteriome, research into lesser explored components of the gut microbiome, including the gut virome, mycobiome, archaeome, and parasitome, is increasingly suggesting relevance in psychiatry. The contribution of microbiomes beyond the gut, including the oral, lung, and small intestinal microbiomes, to human health and pathology should not be overlooked. Increasing both our awareness and understanding of these less traversed fields of research is critical to improving the therapeutic benefits of treatments targeting the gut microbiome, including fecal microbiome transplantation, postbiotics and biogenics, and dietary intervention. Interdisciplinary collaborations integrating systems biology approaches are required to fully elucidate how these different microbial components and distinct microbial niches interact with each other and their human hosts. Excitingly, we may be at the start of the next microbiome revolution, and thus one step closer to informing the field of precision psychiatry to improve outcomes for those living with mental illness.}, } @article {pmid37655340, year = {2023}, author = {Zhang, Q and Zhou, J and Zhang, X and Mao, R and Zhang, C}, title = {Mendelian randomization supports causality between gut microbiota and chronic hepatitis B.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1243811}, pmid = {37655340}, issn = {1664-302X}, abstract = {BACKGROUND: Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.

METHODS: Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.

RESULTS: According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).

CONCLUSION: In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.}, } @article {pmid37654676, year = {2023}, author = {Jiang, Y and Cui, W and Zhang, Y and Wang, T and Zheng, X and Li, H and Shang, J}, title = {FG-4592 relieves diabetic kidney disease severity by influencing metabolic profiles via gut microbiota reconstruction in both human and mouse models.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1195441}, pmid = {37654676}, issn = {1664-042X}, abstract = {Objective: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is highly associated with devastating outcomes. Hypoxia-inducible factor (HIF), the main transcription factor that regulates cellular responses to hypoxia, plays an important role in regulating erythropoietin (EPO) synthesis. FG-4592 is the HIF stabilizer that is widely used in patients with renal anemia. We investigated the effect of FG-4592 on DKD phenotypes and the pharmacologic mechanism from the perspective of gut microbiota and systemic metabolism. Design: We collected the clinical data of 73 participants, including 40 DKD patients with combined renal anemia treated with FG-4592, and 33 clinical index-matched DKD patients without FG-4592 treatment from The First Affiliated Hospital of Zhengzhou University at the beginning and after a 3-6-month follow-up period. We established DKD mouse models treated by FG-4592 and performed fecal microbiota transplantation from FG-4592-treated DKD mice to investigate the effects of FG-4592 on DKD and to understand this mechanism from a microbial perspective. Untargeted metabolome-microbiome combined analysis was implemented to globally delineate the mechanism of FG-4592 from both microbial and metabolomic aspects. Result: DKD phenotypes significantly improved after 3-6 months of FG-4592 treatment in DKD patients combined with renal anemia, including a decreased level of systolic blood pressure, serum creatinine, and increased estimated glomerular infiltration rate. Such effects were also achieved in the DKD mouse model treated with FG-4592 and can be also induced by FG-4592-influenced gut microbiota. Untargeted plasma metabolomics-gut microbiota analysis showed that FG-4592 dramatically altered both the microbial and metabolic profiles of DKD mice and relieved DKD phenotypes via upregulating beneficial gut microbiota-associated metabolites. Conclusion: FG-4592 can globally relieve the symptoms of DKD patients combined with renal anemia. In the animal experiment, FG-4592 can reconstruct the intestinal microbial profiles of DKD to further upregulate the production of gut-associated beneficial metabolites, subsequently improving DKD phenotypes.}, } @article {pmid37654670, year = {2023}, author = {Malard, F and Loschi, M and Huynh, A and Cluzeau, T and Guenounou, S and Legrand, F and Magro, L and Orvain, C and Charbonnier, A and Panz-Klapuch, M and Desmier, D and Mear, JB and Cornillon, J and Robin, C and Daguindau, E and Bilger, K and Vehreschild, MJGT and Chevallier, P and Labussière-Wallet, H and Mediavilla, C and Couturier, MA and Bulabois, CE and Camus, V and Chantepie, S and Ceballos, P and Gaugler, B and Holler, E and Doré, J and Prestat, E and Gasc, C and Plantamura, E and Mohty, M}, title = {Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial.}, journal = {EClinicalMedicine}, volume = {62}, number = {}, pages = {102111}, pmid = {37654670}, issn = {2589-5370}, abstract = {BACKGROUND: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD.

METHODS: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980).

FINDINGS: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters.

INTERPRETATION: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation.

FUNDING: MaaT Pharma.}, } @article {pmid37652953, year = {2023}, author = {Wu, J and Li, C and Gao, P and Zhang, C and Zhang, P and Zhang, L and Dai, C and Zhang, K and Shi, B and Liu, M and Zheng, J and Pan, B and Chen, Z and Zhang, C and Liao, W and Pan, W and Fang, W and Chen, C}, title = {Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {326}, pmid = {37652953}, issn = {2059-3635}, support = {82072257//National Natural Science Foundation of China (National Science Foundation of China)/ ; No. 20DZ2253700, 20DZ2272000, 21410750500 and 22Y21900500//Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)/ ; }, abstract = {Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.}, } @article {pmid37648006, year = {2023}, author = {Li, X and Fu, B and Zhao, C and Hu, J and Zhang, X and Fu, Y and She, X and Gu, C and Cheng, M and Wang, F and Song, X and Dai, J and Yin, J and Fu, Y and Zheng, P and Wu, F and Zhu, Y and Ma, K and Gao, X and Wang, M and Zeng, Q and Cui, B}, title = {Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {221-239}, doi = {10.1016/j.bbi.2023.08.021}, pmid = {37648006}, issn = {1090-2139}, abstract = {Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.}, } @article {pmid37646895, year = {2023}, author = {Reasoner, SA and Nicholson, MR}, title = {Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease.}, journal = {Current gastroenterology reports}, volume = {}, number = {}, pages = {}, pmid = {37646895}, issn = {1534-312X}, support = {T32GM007347/GF/NIH HHS/United States ; K23AI156132/GF/NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Children with inflammatory bowel disease (IBD) are at increased risk of C. difficile infection (CDI) and experience worse outcomes associated with an infection. In this article, we review recent research on the incidence, diagnosis, complications, and treatment options for CDI in children with IBD.

RECENT FINDINGS: Children with IBD have an elevated incidence of CDI, but their CDI risk does not associate with established risk factors in adults with IBD. Existing testing methodologies are inadequate at differentiating CDI from C. difficile colonization in children with IBD. Fecal microbiota transplantation offers a durable cure for recurrent CDI. CDI remains a frequent occurrence in children with IBD. Careful clinical monitoring should be used to diagnose CDI and patients with co-occurring IBD and CDI require careful surveillance for worse outcomes. Future research should explore the optimal diagnosis and treatment modalities in this unique patient population.}, } @article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, } @article {pmid37641627, year = {2023}, author = {Zhang, D and Liu, Z and Bai, F}, title = {Roles of Gut Microbiota in Alcoholic Liver Disease.}, journal = {International journal of general medicine}, volume = {16}, number = {}, pages = {3735-3746}, pmid = {37641627}, issn = {1178-7074}, abstract = {Alcoholic liver disease (ALD)-one of the most common liver diseases - involves a wide range of disorders, including asymptomatic hepatic steatosis, alcoholic hepatitis (AH), liver fibrosis, and cirrhosis. Alcohol consumption induces a weakened gut barrier and changes in the composition of the gut microbiota. The presence of CYP2E1 and its elevated levels in the gastrointestinal tract after alcohol exposure lead to elevated levels of ROS and acetaldehyde, inducing inflammation and oxidative damage in the gut. At the same time, the influx of harmful molecules such as the bacterial endotoxin LPS and peptidogly from gut dysbiosis can induce intestinal inflammation and oxidative damage, further compromising the intestinal mucosal barrier. In this process, various oxidative stress-mediated post-translational modifications (PTMs) play an important role in the integrity of the barrier, eg, the presence of acetaldehyde will result in the sustained phosphorylation of several paracellular proteins (occludin and zona occludens-1), which can lead to intestinal leakage. Eventually, persistent oxidative stress, LPS infiltration and hepatocyte damage through the enterohepatic circulation will lead to hepatic stellate cell activation and hepatic fibrosis. In addition, probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), bioengineered bacteria, gut-restricted FXR agonists and others are promising therapeutic approaches that can alter gut microbiota composition to improve ALD. In the future, there will be new challenges to study the interactions between the genetics of individuals with ALD and their gut microbiome, to provide personalized interventions targeting the gut-liver axis, and to develop better techniques to measure microbial communities and metabolites in the body.}, } @article {pmid37641043, year = {2023}, author = {Wu, L and Yuan, Q and Wu, L and Hua-Xiang Xia, H and Zhong, M and Liu, T and Ye, X and Luo, D and Xu, J and Xie, W and He, X and Cai, J}, title = {Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {291}, pmid = {37641043}, issn = {1471-230X}, support = {2023A04J1850//Science and Technology Program of Guangzhou, China/ ; A2020172//Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//Scientific Research Project of Guangdong Provincial Bureau of traditional Chinese Medicine/ ; 2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; }, mesh = {Humans ; Follow-Up Studies ; Retrospective Studies ; *Constipation/therapy ; Defecation ; *Microbiota ; }, abstract = {BACKGROUND: The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets.

METHODS: The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed.

RESULTS: Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy.

CONCLUSIONS: WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.}, } @article {pmid37640503, year = {2023}, author = {Muino, AF and Compo, NR and Everett, BM and Abrahams, DF and Baldwin, MK and James, TN and Wanner, SE and Perkins, MJ and Parr, CE and Wiltshire, ND and Miedel, EL and Engelman, RW}, title = {Equipment and Methods for Concurrently Housing Germfree and Gnotobiotic Mice in the Same Room.}, journal = {Journal of the American Association for Laboratory Animal Science : JAALAS}, volume = {}, number = {}, pages = {}, doi = {10.30802/AALAS-JAALAS-23-000019}, pmid = {37640503}, issn = {2769-6677}, abstract = {Here, we combined the use of 2 technologies that have not previously been used together-a positively pressurized isolatorIVC (IsoIVC-P) and a modular isolator with integrated vaporized hydrogen peroxide (VHP) technology-to develop highlytractable and scalable methods to support long-term maintenance of germfree mouse colonies and the concurrent use of germfreeand gnotobiotic mice in the same room. This space-efficient system increases the practicality of microbiome studies.Specifically, the exterior surfaces of microbially similar IsoIVC-P were sterilized by using VHP prior to opening the cagesand handling the mice therein. This space-efficient system increases the feasibility of microbiome studies. After over 74 wkof experimentation and handling equivalent to more than 1,379,693 germfree mouse-days, we determined that the methodand practices we developed have a weekly performance metric of 0.0001 sterility breaks per husbandry unit; this rate is comparableto the isolator 'gold standard.' These data were achieved without adverse incidents while maintaining an AlteredSchaedler Flora colony and multiple gnotobiotic studies involving fecal microbial transplants in the same room. Our novelIsoIVC-P-VHP workstation housing system thus improves microbiome research efficiency, eliminates hazards, and reducesrisks associated with traditional methods.}, } @article {pmid37640378, year = {2023}, author = {Hwang, SW and Kim, MK and Kweon, MN}, title = {Gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis: a review.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00019}, pmid = {37640378}, issn = {1598-9100}, abstract = {Immune checkpoint inhibitors have dramatically revolutionized the therapeutic landscape for patients with advanced malignancies. Recently, convincing evidence has shown meaningful influence of gut microbiome on human immune system. With the complex link between gut microbiome, host immunity and cancer, the variations in the gut microbiota may influence the efficacy of immune checkpoint inhibitors. Indeed, some bacterial species have been reported to be predictive for cancer outcome in patients treated with immune checkpoint inhibitors. Although immune checkpoint inhibitors are currently proven to be an effective anti-tumor treatment, they can induce a distinct form of toxicity, termed immune-related adverse events. Immune-related colitis is one of the common toxicities from immune checkpoint inhibitors, and it might preclude the cancer therapy in severe or refractory cases. The manipulation of gut microbiome by fecal microbiota transplantation or probiotics administration has been suggested as one of the methods to enhance anti-tumor effects and decrease the risk of immune-related colitis. Here we review the role of gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis to provide a new insight for better anti-cancer therapy.}, } @article {pmid37639247, year = {2023}, author = {Bretthauer, M and Wieszczy, P and Løberg, M and Kaminski, MF and Werner, TF and Helsingen, LM and Mori, Y and Holme, Ø and Adami, HO and Kalager, M}, title = {Estimated Lifetime Gained With Cancer Screening Tests: A Meta-Analysis of Randomized Clinical Trials.}, journal = {JAMA internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamainternmed.2023.3798}, pmid = {37639247}, issn = {2168-6114}, abstract = {IMPORTANCE: Cancer screening tests are promoted to save life by increasing longevity, but it is unknown whether people will live longer with commonly used cancer screening tests.

OBJECTIVE: To estimate lifetime gained with cancer screening.

DATA SOURCES: A systematic review and meta-analysis was conducted of randomized clinical trials with more than 9 years of follow-up reporting all-cause mortality and estimated lifetime gained for 6 commonly used cancer screening tests, comparing screening with no screening. The analysis included the general population. MEDLINE and the Cochrane library databases were searched, and the last search was performed October 12, 2022.

STUDY SELECTION: Mammography screening for breast cancer; colonoscopy, sigmoidoscopy, or fecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; or prostate-specific antigen testing for prostate cancer.

DATA EXTRACTION AND SYNTHESIS: Searches and selection criteria followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Data were independently extracted by a single observer, and pooled analysis of clinical trials was used for analyses.

MAIN OUTCOMES AND MEASURES: Life-years gained by screening was calculated as the difference in observed lifetime in the screening vs the no screening groups and computed absolute lifetime gained in days with 95% CIs for each screening test from meta-analyses or single randomized clinical trials.

RESULTS: In total, 2 111 958 individuals enrolled in randomized clinical trials comparing screening with no screening using 6 different tests were eligible. Median follow-up was 10 years for computed tomography, prostate-specific antigen testing, and colonoscopy; 13 years for mammography; and 15 years for sigmoidoscopy and FOBT. The only screening test with a significant lifetime gain was sigmoidoscopy (110 days; 95% CI, 0-274 days). There was no significant difference following mammography (0 days: 95% CI, -190 to 237 days), prostate cancer screening (37 days; 95% CI, -37 to 73 days), colonoscopy (37 days; 95% CI, -146 to 146 days), FOBT screening every year or every other year (0 days; 95% CI, -70.7 to 70.7 days), and lung cancer screening (107 days; 95% CI, -286 days to 430 days).

CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy.}, } @article {pmid37637989, year = {2023}, author = {Contarino, MF and van Hilten, JJ and Kuijper, EJ}, title = {Targeting the Gut-Brain Axis with Fecal Microbiota Transplantation: Considerations on a Potential Novel Treatment for Parkinson's Disease.}, journal = {Movement disorders clinical practice}, volume = {10}, number = {Suppl 2}, pages = {S21-S25}, pmid = {37637989}, issn = {2330-1619}, } @article {pmid37637623, year = {2023}, author = {Ratna, HVK and Jeyaraman, M and Yadav, S and Jeyaraman, N and Nallakumarasamy, A}, title = {Is Dysbiotic Gut the Cause of Low Back Pain?.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42496}, pmid = {37637623}, issn = {2168-8184}, abstract = {Low back pain (LBP) is the foremost cause of disability that affects the day-to-day activities of millions of people worldwide. The putative trigger of LBP is linked to the gut microbiome (GM) and its dysbiotic environment. With the concept of GM, various disease pathogenesis has been revisited with plausible crosstalks and micromolecular mimicry. In the normal intervertebral disc (IVD), Firmicutes and Actinobacteria were found in abundance. The blood-disc barrier protects IVD from systemic infection, resists inflammation, and halts the immune surveillance of the inner aspects of IVD. The insights into microbial ecology will broaden our horizons in GM and IVD degeneration in LBP cases. However, an improved understanding of GM and back pain has to be explored in large-scale individuals with varied timescales to validate the above findings. The role of GM (diet, prebiotics, probiotics, and fecal microbiota transplantation) in pain modulation can form novel therapies in cases of LBP.}, } @article {pmid37636278, year = {2023}, author = {Yin, J and Li, Y and Tian, Y and Zhou, F and Ma, J and Xia, S and Yang, T and Ma, L and Zeng, Q and Liu, G and Yin, Y and Huang, X}, title = {Obese Ningxiang pig-derived microbiota rewires carnitine metabolism to promote muscle fatty acid deposition in lean DLY pigs.}, journal = {Innovation (Cambridge (Mass.))}, volume = {4}, number = {5}, pages = {100486}, pmid = {37636278}, issn = {2666-6758}, abstract = {The gut microbiota consistently shows strong correlations with lipid metabolism in humans and animals, and whether the gut microbiota contributes to muscle fatty acid (FA) deposition and meat traits in farm animals has not been fully resolved. In this study, we aimed to unveil the microbial mechanisms underlying muscle FA deposition in pigs. First, we systematically revealed the correlation between the gut microbiome and muscle FA levels in 43 obese Ningxiang pigs and 50 lean Duroc Landrace Yorkshire (DLY) pigs. Mutual fecal microbial transplantation showed that the obese Ningxiang pig-derived microbiota increased the muscle FA content and improved meat quality by reshaping the gut microbial composition in lean DLY pigs. Lactobacillus reuteri has been identified as a potential microbial biomarker in obese Ningxiang pig-derived microbiota-challenged DLY pigs. A gavage experiment using lean DLY pigs confirmed that L. reuteri XL0930 isolated from obese Ningxiang pigs was the causal species that increased the muscle FA content. Mechanistically, SLC22A5, a carnitine transporter, was downregulated in L. reuteri XL0930-fed DLY pigs, resulting in reduced muscle carnitine levels. Muscle and intestinal L-carnitine levels, which correlated with the muscle FA content, impeded fat synthesis and FA accumulation in in vitro and in vivo models. In conclusion, we uncovered an unexpected and important role of the obese Ningxiang pig-derived microbiota in regulating muscle FA metabolism via the SLC22A5-mediated carnitine system.}, } @article {pmid37630824, year = {2023}, author = {Yang, JC and Troutman, R and Buri, H and Gutta, A and Situ, J and Aja, E and Jacobs, JP}, title = {Ileal Dysbiosis Is Associated with Increased Acoustic Startle in the 22q11.2 Microdeletion Mouse Model of Schizophrenia.}, journal = {Nutrients}, volume = {15}, number = {16}, pages = {}, pmid = {37630824}, issn = {2072-6643}, support = {NA//University of California Los Angeles/ ; }, mesh = {Humans ; Animals ; Mice ; *Dysbiosis ; Reflex, Startle ; *Schizophrenia/genetics ; Disease Models, Animal ; Acoustics ; Ileum ; }, abstract = {Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut microbiome plays a critical role in mediating SCZ-linked physiology and behavior. To date, only one animal model (a metabotropic glutamate receptor 5 knockout) of SCZ has been reported to recapitulate SCZ-linked gut dysbiosis. Since human 22q11.2 microdeletion syndrome is associated with increased risk of SCZ, we investigated whether the 22q11.2 microdeletion ("Q22") mouse model of SCZ exhibits both SCZ-linked behaviors and intestinal dysbiosis. We demonstrated that Q22 mice display increased acoustic startle response and ileal (but not colonic) dysbiosis, which may be due to the role of the ileum as an intestinal region with high immune and neuroimmune activity. We additionally identified a negative correlation between the abundance of a Streptococcus species in the ilea of Q22 mice and their acoustic startle response, providing early evidence of a gut-brain relationship in these mice. Given the translational relevance of this mouse model, our work suggests that Q22 mice could have considerable utility in preclinical research probing the relationship between gut dysbiosis and the gut-brain axis in the pathogenesis of SCZ.}, } @article {pmid37630649, year = {2023}, author = {Salmeri, N and Sinagra, E and Dolci, C and Buzzaccarini, G and Sozzi, G and Sutera, M and Candiani, M and Ungaro, F and Massimino, L and Danese, S and Mandarino, FV}, title = {Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630649}, issn = {2076-2607}, abstract = {Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.}, } @article {pmid37630643, year = {2023}, author = {Kappéter, Á and Sipos, D and Varga, A and Vigvári, S and Halda-Kiss, B and Péterfi, Z}, title = {Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630643}, issn = {2076-2607}, abstract = {Migraine is a painful neurological condition characterized by severe pain on one or both sides of the head. It may be linked to changes in the gut microbiota, which are influenced by antibiotic use and other factors. Dysbiosis, which develops and persists as a result of earlier antibiotic therapy, changes the composition of the intestinal flora, and can lead to the development of various diseases such as metabolic disorders, obesity, hematological malignancies, neurological or behavioral disorders, and migraine. Metabolites produced by the gut microbiome have been shown to influence the gut-brain axis. The use of probiotics as a dietary supplement may reduce the number and severity of migraine episodes. Dietary strategies can affect the course of migraines and are a valuable tool for improving migraine management. With fecal microbiota transplantation, gut microbial restoration is more effective and more durable. Changes after fecal microbiota transplantation were studied in detail, and many data help us to interpret the successful interventions. The microbiological alteration of the gut microflora can lead to normalization of the inflammatory mediators, the serotonin pathway, and influence the frequency and intensity of migraine pain.}, } @article {pmid37630549, year = {2023}, author = {Munley, JA and Kirkpatrick, SL and Gillies, GS and Bible, LE and Efron, PA and Nagpal, R and Mohr, AM}, title = {The Intestinal Microbiome after Traumatic Injury.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630549}, issn = {2076-2607}, support = {T32 GM-008721/GM/NIGMS NIH HHS/United States ; }, abstract = {The intestinal microbiome plays a critical role in host immune function and homeostasis. Patients suffering from-as well as models representing-multiple traumatic injuries, isolated organ system trauma, and various severities of traumatic injury have been studied as an area of interest in the dysregulation of immune function and systemic inflammation which occur after trauma. These studies also demonstrate changes in gut microbiome diversity and even microbial composition, with a transition to a pathobiome state. In addition, sex has been identified as a biological variable influencing alterations in the microbiome after trauma. Therapeutics such as fecal transplantation have been utilized to ameliorate not only these microbiome changes but may also play a role in recovery postinjury. This review summarizes the alterations in the gut microbiome that occur postinjury, either in isolated injury or multiple injuries, along with proposed mechanisms for these changes and future directions for the field.}, } @article {pmid37630442, year = {2023}, author = {Ishibashi, R and Matsuhisa, R and Nomoto, M and Chudan, S and Nishikawa, M and Tabuchi, Y and Ikushiro, S and Nagai, Y and Furusawa, Y}, title = {Effect of Oral Administration of Polyethylene Glycol 400 on Gut Microbiota Composition and Diet-Induced Obesity in Mice.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630442}, issn = {2076-2607}, support = {20K05929//JSPS KAKENHI/ ; n/a//Takeda Science Foundation/ ; n/a//Kanamori Foundation/ ; }, abstract = {Polyethylene glycol (PEG) is a commonly used dispersant for oral administration of hydrophobic agents. PEG is partly absorbed in the small intestine, and the unabsorbed fraction reaches the large intestine; thus, oral administration of PEG may impact the gut microbial community. However, to the best of our knowledge, no study evaluated the effects of PEG on gut commensal bacteria. Herein, we aimed to determine whether oral administration of PEG modifies the gut microbiota. Administration of PEG400 and PEG4000 altered gut microbial diversity in a concentration-dependent manner. Taxonomic analysis revealed that Akkermansia muciniphila and particularly Parabacteroides goldsteinii were overrepresented in mice administered with 40% PEG. PEG400 administration ameliorated the high-fat diet (HFD)-induced obesity and adipose tissue inflammation. Fecal microbiome transplantation from PEG400-administered donors counteracted the HFD-induced body and epididymal adipose tissue weight gain, indicating that PEG400-associated bacteria are responsible for the anti-obesity effect. Conversely, carboxymethyl cellulose, also used as a dispersant, did not affect the abundance of these two bacterial species or HFD-induced obesity. In conclusion, we demonstrated that oral administration of a high concentration of PEG400 (40%) alters the gut microbiota composition and ameliorates HFD-induced obesity.}, } @article {pmid37629716, year = {2023}, author = {Abenavoli, L and Montori, M and Svegliati Baroni, G and Argenziano, ME and Giorgi, F and Scarlata, GGM and Ponziani, F and Scarpellini, E}, title = {Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {8}, pages = {}, doi = {10.3390/medicina59081427}, pmid = {37629716}, issn = {1648-9144}, abstract = {Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI's treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.}, } @article {pmid37627687, year = {2023}, author = {MacNair, CR and Tsai, CN and Rutherford, ST and Tan, MW}, title = {Returning to Nature for the Next Generation of Antimicrobial Therapeutics.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/antibiotics12081267}, pmid = {37627687}, issn = {2079-6382}, support = {NA//Genentech/ ; }, abstract = {Antibiotics found in and inspired by nature are life-saving cures for bacterial infections and have enabled modern medicine. However, the rise in resistance necessitates the discovery and development of novel antibiotics and alternative treatment strategies to prevent the return to a pre-antibiotic era. Once again, nature can serve as a source for new therapies in the form of natural product antibiotics and microbiota-based therapies. Screening of soil bacteria, particularly actinomycetes, identified most of the antibiotics used in the clinic today, but the rediscovery of existing molecules prompted a shift away from natural product discovery. Next-generation sequencing technologies and bioinformatics advances have revealed the untapped metabolic potential harbored within the genomes of environmental microbes. In this review, we first highlight current strategies for mining this untapped chemical space, including approaches to activate silent biosynthetic gene clusters and in situ culturing methods. Next, we describe how using live microbes in microbiota-based therapies can simultaneously leverage many of the diverse antimicrobial mechanisms found in nature to treat disease and the impressive efficacy of fecal microbiome transplantation and bacterial consortia on infection. Nature-provided antibiotics are some of the most important drugs in human history, and new technologies and approaches show that nature will continue to offer valuable inspiration for the next generation of antibacterial therapeutics.}, } @article {pmid37625154, year = {2023}, author = {Gratacós-Ginès, J and Bruguera, P and Pérez-Guasch, M and López-Lazcano, A and Borràs, R and Hernández-Évole, H and Pons-Cabrera, MT and Lligoña, A and Bataller, R and Ginès, P and López-Pelayo, H and Pose, E}, title = {Medications for alcohol use disorder promote abstinence in alcohol-related cirrhosis: results from a systematic review and meta-analysis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000570}, pmid = {37625154}, issn = {1527-3350}, abstract = {BACKGROUND: the role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce. Approach & results: we performed a systematic review and meta-analysis according to PRISMA guidelines on the efficacy of MAUD in patients with cirrhosis. Search was conducted in PubMed, Embase and Scopus, including all studies until May 2022. Population was defined as patients with AUD and cirrhosis. Primary outcome was alcohol abstinence (AA). Safety was a secondary outcome. We performed a random-effects analysis and expressed the results as relative risk (RR) of alcohol consumption. Heterogeneity was measured by I2. Out of 4,095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1) and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies and 4 were randomized clinical trials (RCT). Only RCTs were included in the meta-analysis. MAUD were associated with a reduced rate of alcohol consumption [RR = 0.68 (CI 0.48-0.97), P = 0.03], increasing AA by 32% compared to placebo or standard treatment, despite high heterogeneity (I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.

CONCLUSION: MAUD in patients with cirrhosis are effective in promoting AA and have a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.}, } @article {pmid37624549, year = {2023}, author = {Pal, P and Shastry, RP}, title = {Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {37624549}, issn = {1874-9356}, support = {ICMR/5/13/84/2020/NCD-III dated 16/03/2021//ICMR-DHR, Government of India, New Delhi/ ; }, abstract = {The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.}, } @article {pmid37624256, year = {2023}, author = {Mafra, D and Kemp, JA and Borges, NA and Wong, M and Stenvinkel, P}, title = {Gut Microbiota Interventions to Retain Residual Kidney Function.}, journal = {Toxins}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/toxins15080499}, pmid = {37624256}, issn = {2072-6651}, abstract = {Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.}, } @article {pmid37624046, year = {2023}, author = {Ma, C and McCallen, J and McVey, JC and Trehan, R and Bauer, K and Zhang, Q and Ruf, B and Wang, S and Lai, CW and Trinchieri, G and Berzofsky, JA and Korangy, F and Greten, TF}, title = {CSF-1R+ Macrophages Control the Gut Microbiome-enhanced Liver Invariant NKT Function through IL-18.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {}, number = {}, pages = {}, doi = {10.4049/jimmunol.2200854}, pmid = {37624046}, issn = {1550-6606}, abstract = {The gut microbiome is an important modulator of the host immune system. In this study, we found that altering the gut microbiome by oral vancomycin increases liver invariant NKT (iNKT) cell function. Enhanced iNKT cytokine production and activation marker expression were observed in vancomycin-treated mice following both Ag-specific and Ag-independent in vivo iNKT stimulations, with a more prominent effect in the liver than in the spleen. Fecal transplantation studies demonstrated that the iNKT functional regulation is mediated by altering the gut microbiome but uncoupled from the modulation of iNKT cell population size. Interestingly, when stimulated in vitro, iNKT cells from vancomycin-treated mice did not show increased activation, suggesting an indirect regulation. iNKT cells expressed high levels of IL-18 receptor, and vancomycin increased the expression of IL-18 in the liver. Blocking IL-18 by neutralizing Ab or using genetically deficient mice attenuated the enhanced iNKT activation. Liver macrophages were identified as a major source of IL-18. General macrophage depletion by clodronate abolished this iNKT activation. Using anti-CSF-1R depletion or LyzCrexCSF-1RLsL-DTR mice identified CSF-1R+ macrophages as a critical modulator of iNKT function. Vancomycin treatment had no effect on iNKT cell function in vivo in IL-18 knockout macrophage reconstituted mice. Together, our results demonstrate that the gut microbiome controls liver iNKT function via regulating CSF-1R+ macrophages to produce IL-18.}, } @article {pmid37623261, year = {2023}, author = {Sanekommu, H and Taj, S and Mah Noor, R and Umair Akmal, M and Akhtar, R and Hossain, M and Asif, A}, title = {Probiotics and Fecal Transplant: An Intervention in Delaying Chronic Kidney Disease Progression?.}, journal = {Clinics and practice}, volume = {13}, number = {4}, pages = {881-888}, pmid = {37623261}, issn = {2039-7275}, abstract = {Chronic kidney disease (CKD) is a global health challenge affecting nearly 700 million people worldwide. In the United States alone, the Medicare costs for CKD management has reached nearly USD 80 billion per year. While reversing CKD may be possible in the future, current strategies aim to slow its progression. For the most part, current management strategies have focused on employing Renin Angiotensin Aldosterone (RAS) inhibitors and optimizing blood pressure and diabetes mellitus control. Emerging data are showing that a disruption of the gut-kidney axis has a significant impact on delaying CKD progression. Recent investigations have documented promising results in using microbiota-based interventions to better manage CKD. This review will summarize the current evidence and explore future possibilities on the use of probiotics, prebiotics, synbiotics, and fecal microbial transplant to reduce CKD progression.}, } @article {pmid37621873, year = {2023}, author = {Fu, X and Tan, H and Huang, L and Chen, W and Ren, X and Chen, D}, title = {Gut microbiota and eye diseases: a bibliometric study and visualization analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1225859}, pmid = {37621873}, issn = {2235-2988}, abstract = {INTRODUCTION: Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.

METHODS: We search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.

RESULTS: A total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology & Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.

CONCLUSIONS: In conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.}, } @article {pmid37621810, year = {2023}, author = {Cheng, X and Li, X and Yang, X and Fang, S and Wang, Z and Liu, T and Zheng, M and Zhai, M and Yang, Z and Shen, T}, title = {Successful Treatment of pMMR MSS IVB Colorectal Cancer Using Anti-VEGF and Anti-PD-1 Therapy in Combination of Gut Microbiota Transplantation: A Case Report.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42347}, pmid = {37621810}, issn = {2168-8184}, abstract = {Immune checkpoint inhibitors (ICI) have shown great promise in treating advanced or metastatic colorectal cancer (mCRC), especially for CRC patients with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). For the remainder of CRC patients presenting with proficient mismatch repair (pMMR) and microsatellite stable (MSS) or low microsatellite instability (MSI-L), ICI showed a low-level response. This study describes a 57-year-old Chinese man diagnosed with pMMR MSS IVb CRC with liver metastasis. Primarily, the patient was administered two consecutive treatments, one composed of an anti-EGFR and modified FOLFOX6 and the other composed of an anti-VEGF and FOLFOXIRI. Due to severe chemotherapy side effects, the patient discontinued treatment and decided to take a third investigational treatment, where an anti-PD-1 and an anti-VEGF were given in combination with fecal microbiota transplantation (FMT) capsules. The patient achieved a partial response (PR), and the tumor size decreased to the extent amenable to surgical resection. After surgery, the patient achieved a pathological complete response (pCR). Patients with pMMR MSS or MSI-L hardly benefit from anti-PD-1 immunotherapy. This study indicated that, to a limited extent, FMT might improve the response to ICI for pMMR MSS CRC patients.}, } @article {pmid37619529, year = {2023}, author = {Sumida, K and Pierre, JF and Yuzefpolskaya, M and Colombo, PC and Demmer, RT and Kovesdy, CP}, title = {Gut Microbiota-Targeted Interventions in the Management of Chronic Kidney Disease.}, journal = {Seminars in nephrology}, volume = {43}, number = {2}, pages = {151408}, doi = {10.1016/j.semnephrol.2023.151408}, pmid = {37619529}, issn = {1558-4488}, abstract = {Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota-targeted interventions in the management of CKD.}, } @article {pmid37615494, year = {2023}, author = {Zhanel, GG and Keynan, R and Keynan, Y and Karlowsky, JA}, title = {The role of Fecal Microbiota Transplantation (FMT) in treating patients with multiple sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14737175.2023.2250919}, pmid = {37615494}, issn = {1744-8360}, abstract = {INTRODUCTION: The associations between multiple sclerosis (MS) and altered intestinal microbiomes have clinicians considering the use of fecal microbiota transplantation (FMT). Animal data suggests that administering FMT from people with MS into healthy mice results in a microbiome with decreased abundance of Sutterella, reduced anti-inflammatory signals, increase in inflammation and experimental autoimmune encephalomyelitis (EAE). Animal studies that administered FMT (from normal healthy donors) into mice resulted in slowing down EAE development relieving symptoms, improving BBB integrity and restoration of microbiota diversity. Human studies indicated clinical benefits of FMT (from healthy donors) in people with MS including: improved intestinal motility and motor ability which lasted at least for the duration of the studies, ranging from 2 to 15 years.

AREAS COVERED: The authors discuss the efficacy and safety of FMT in treatment of experimental MS in animals and humans with MS. A literature search was performed via PubMed (up to July 2023), using the key words: multiple sclerosis, fecal microbiota transplantation, microbiome.

EXPERT OPINION: Limited associative data do not provide an understanding of role of FMT in the treatment for MS. Until appropriately designed randomized comparative trials which are underway, are completed, we cannot recommend routine use of FMT in people with MS.}, } @article {pmid37615438, year = {2023}, author = {Fadlallah, S and Bitar, ER and Hussein, H and Jallad, MA and Matar, GM and Rahal, EA}, title = {The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0204223}, doi = {10.1128/spectrum.02042-23}, pmid = {37615438}, issn = {2165-0497}, abstract = {Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. IMPORTANCE Epstein-Barr virus (EBV) DNA alters the composition and diversity of the gut microbiota in a rheumatoid arthritis (RA) mouse model. These induced changes are associated with enhanced severity of symptoms. This better understanding of the various factors involved in the development of RA will possibly help in creating individualized treatments for RA patients including target mediators triggered by viral DNA. Given that a large swathe of the population harbors EBV, a significant proportion of subjects with arthritis may benefit from possible approaches that target EBV or mediators triggered by this virus.}, } @article {pmid37615344, year = {2023}, author = {Hyde, MK and Masser, BM and Spears, L}, title = {"Why don't you want my poop?" Willing stool donor's experiences of being ineligible to donate intestinal microbiota.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.17516}, pmid = {37615344}, issn = {1537-2995}, support = {//The University of Queensland (UQ) Vice-Chancellor's Strategic Funds/ ; //Australian governments/ ; }, abstract = {BACKGROUND: Blood collection agencies (BCAs) hosting stool (fecal or poo) donor programs report high rates of donor deferral. However, the impact of deferral on willing donors, in terms of personal well-being and future engagement with BCAs, remains unexplored. Accordingly, we surveyed those attempting to donate intestinal microbiota about their experience of being ineligible.

STUDY DESIGN AND METHODS: A total of 196 potential stool donors from Australia's BCA (>90% blood/blood product donors) completed the first stage of eligibility screening and then an online survey once notified of their ineligibility. Respondents reported motives for donating, perceptions of screening and improvements needed, experience of being told they are ineligible, and their feelings about this.

RESULTS: Over 80% of participants were ineligible to donate. Of those ineligible, 58% did not know why they were ineligible resulting in potentially future eligible donors being permanently lost. Motives (>5%) included helping others, being a human substance donor, understanding benefits, curiosity/novelty, and helping science/research. Participants identified they needed clear and timely information during screening and a specific reason for their ineligibility. Participants commonly experienced disappointment, confusion, and calm in response to being ineligible.

DISCUSSION: BCAs need strategies to mitigate the disappointment of ineligible donors, maintain satisfaction with BCAs, and preserve donor identity since many ineligible donors give multiple human substances. BCAs should provide more information about eligibility criteria during early screening stages to reduce disappointment and give personalized information about ineligibility to resolve the confusion. Offering alternative opportunities to give may reduce disappointment and increase ineligible donor engagement.}, } @article {pmid37615334, year = {2023}, author = {Rajapakse, J and Khatiwada, S and Akon, AC and Yu, KL and Shen, S and Zekry, A}, title = {Unveiling the complex relationship between gut microbiota and liver cancer: opportunities for novel therapeutic interventions.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2240031}, doi = {10.1080/19490976.2023.2240031}, pmid = {37615334}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Liver Neoplasms/therapy ; *Carcinoma, Hepatocellular/therapy ; *Gastrointestinal Microbiome ; Bile Acids and Salts ; }, abstract = {Hepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of the immune responses relevant to HCC formation. The pro- or anti-tumor effects of specific bacterial strains or gut microbiota-related metabolites, such as bile acids and short-chain fatty acids, have been highlighted in many human and animal studies. The critical role of the gut microbiota in HCC development has spurred interest in modulating the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation as a potential strategy to improve liver cancer outcomes. Encouragingly, preclinical and clinical studies have demonstrated that modulation of the gut microbiota can ameliorate liver function, reduce inflammation, and inhibit liver tumor growth, underscoring the potential of this approach to improve HCC outcomes. As research continues to unravel the complex and dynamic mechanisms underlying the gut-liver axis, the development of safe and effective interventions to target this pathway for liver cancer prevention and treatment appears to be on the horizon, heralding a significant advance in our ongoing efforts to combat this devastating disease.}, } @article {pmid37610978, year = {2023}, author = {Koning, M and Herrema, H and Nieuwdorp, M and Meijnikman, AS}, title = {Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2226922}, pmid = {37610978}, issn = {1949-0984}, abstract = {Humans possess abundant amounts of microorganisms, including bacteria, fungi, viruses, and archaea, in their gut. Patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in their gut microbiome and an impaired gut barrier function. Preclinical studies emphasize the significance of the gut microbiome in the pathogenesis of NAFLD. In this overview, we explore how adjusting the gut microbiome could serve as an innovative therapeutic strategy for NAFLD. We provide a summary of current information on untargeted techniques such as probiotics and fecal microbiota transplantation, as well as targeted microbiome-focused therapies including engineered bacteria, prebiotics, postbiotics, and phages for the treatment of NAFLD.}, } @article {pmid37610564, year = {2023}, author = {Arcucci, MS and Menendez, L and Orsi, M and Gallo, J and Guzman, L and Busoni, V and Lifschitz, C}, title = {Role of adjuvant Crohn's disease exclusion diet plus enteral nutrition in asymptomatic pediatric Crohn's disease having biochemical activity: A randomized, pilot study.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {37610564}, issn = {0975-0711}, support = {International Cooperation Grant in Child Nutrition of the Spanish Society of Gastroenterology//SEGHNP/ ; Hepatology//SEGHNP/ ; nutrition 2021//SEGHNP/ ; Young Investigator Award of the Latin American Society of Gastroenterology//LASPGHAN/ ; Hepatology//LASPGHAN/ ; Pediatric Nutrition 2022//LASPGHAN/ ; }, abstract = {BACKGROUND: Conventional therapy can result in remission in mild-moderate pediatric Crohn's disease (CD). However, some patients experience loss of response to biological drugs despite increased dosage.

METHODS: We planned to determine that CD exclusion diet plus partial enteral nutrition offers additional benefits in asymptomatic children with CD having elevated fecal calprotectin. A randomized, open-label, pilot, controlled interventional study was conducted in children with CD while on medical treatment and elevated fecal calprotectin on routine testing. Patients continued their medications and were randomized into a group that received CD exclusion diet plus partial enteral nutrition for 12 weeks and one that continued a regular diet.

RESULTS: Twenty-one patients participated: 11 received CD exclusion diet plus partial enteral nutrition and 10, regular diet. Median fecal calprotectin in the CD exclusion diet plus partial enteral nutrition decreased in 9/11 to 50% of baseline, remaining practically unchanged in the regular diet, except for two patients (p = 0.005). Body mass index z-score increased in the CD exclusion diet plus partial enteral nutrition. Only 1/11 patients in the CD exclusion diet plus partial enteral nutrition group, while 4/10 in the regular diet, experienced clinical relapse (p = 0.149). Only one patient in the CD exclusion diet plus partial enteral nutrition, while eight in the regular diet, were considered to need their biologic treatment intensified (p = 0.005); 2/11 in the CD exclusion diet plus partial enteral nutrition had the dose or frequency of the biologic reduced vs. none (0/10) in the regular diet group. The short Pediatric Crohn's Disease Activity Index and anthropometry showed no significant changes in either group.

CONCLUSIONS: Diet therapy could be a useful addition to medications in children with CD in apparent remission, but elevated fecal calprotectin.

TRIAL REGISTRATION: Clinical trial number: NCT05034458.}, } @article {pmid37609255, year = {2023}, author = {Jenior, ML and Leslie, JL and Kolling, GL and Archbald-Pannone, L and Powers, DA and Petri, WA and Papin, JA}, title = {Systems-ecology designed bacterial consortium protects from severe Clostridioides difficile infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.08.08.552483}, pmid = {37609255}, abstract = {Fecal Microbiota Transplant (FMT) is an emerging therapy that has had remarkable success in treatment and prevention of recurrent Clostridioides difficile infection (rCDI). FMT has recently been associated with adverse outcomes such as inadvertent transfer of antimicrobial resistance, necessitating development of more targeted bacteriotherapies. To address this challenge, we developed a novel systems biology pipeline to identify candidate probiotic strains that would be predicted to interrupt C. difficile pathogenesis. Utilizing metagenomic characterization of human FMT donor samples, we identified those metabolic pathways most associated with successful FMTs and reconstructed the metabolism of encoding species to simulate interactions with C. difficile . This analysis resulted in predictions of high levels of cross-feeding for amino acids in species most associated with FMT success. Guided by these in silico models, we assembled consortia of bacteria with increased amino acid cross-feeding which were then validated in vitro . We subsequently tested the consortia in a murine model of CDI, demonstrating total protection from severe CDI through decreased toxin levels, recovered gut microbiota, and increased intestinal eosinophils. These results support the novel framework that amino acid cross-feeding is likely a critical mechanism in the initial resolution of CDI by FMT. Importantly, we conclude that our predictive platform based on predicted and testable metabolic interactions between the microbiota and C. difficile led to a rationally designed biotherapeutic framework that may be extended to other enteric infections.}, } @article {pmid37606962, year = {2023}, author = {Khanna, S and Voth, E}, title = {Therapeutics for Clostridioides difficile infection: molecules and microbes.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2023.2250716}, pmid = {37606962}, issn = {1747-4132}, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a major healthcare problem in the developed world, and effective management of recurrent infection remains one of the biggest challenges. Several advances have occurred in the management of CDI and in the last 15 years, multiple new agents have been tested. Since 2011, four new products have been approved by the United States FDA for treatment of CDI or prevention of recurrent CDI.

AREAS COVERED: This review focuses on therapeutics of CDI and includes sections on primary prevention, management of active infection and prevention of recurrent CDI. Specifically, data are included on fecal microbiota transplantation and live biotherapeutics. A comprehensive search of several databases including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from inception to NaN Invalid Date NaN was conducted.

EXPERT OPINION: Metronidazole is no longer advised for management of outpatient CDI. The preferred medication of choice for a first episode is oral vancomycin or fidaxomicin. For those patients who recur after the first episode, vancomycin taper pulse or fidaxomicin can be used. Intravenous bezlotoxumab, a monoclonal antibody, is available to prevent recurrences. There are now two FDA approved microbiome-based therapies or live biotherapeutics for prevention of recurrent CDI, for any recurrent CDI and not necessarily multiply recurrent C difficile. Fecal microbiota transplantation remains available in limited settings for recurrent CDI.}, } @article {pmid37606431, year = {2023}, author = {Jaramillo, AP and Castells, J and Ibrahimli, S and Siegel, S}, title = {Recurrent Multidrug-Resistant Clostridium difficile Infection Secondary to Ulcerative Colitis a Case Report.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {37606431}, issn = {2076-3271}, mesh = {Female ; Humans ; *Colitis, Ulcerative/complications/drug therapy ; *Clostridium Infections/complications/drug therapy ; Mesalamine ; Adalimumab ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {IBD consists of two diseases-CD and UC-that affect the digestive tract, with a greater affinity for the large bowel. In this case report, we focus on one of its most common complications. CDI is a pathology that is mostly secondary to UC. Another cause of this bacterial infection is established after the use of antibiotics, most commonly at the hospital level. Around 20 percent of CDI persists because of a chronic dysbiosis of the microbiota and low levels of antibodies against CD toxins. In this case report, we demonstrated mdCDI in a young woman after treatment with multiple drug therapies as well as with semi-invasive procedures as follows: antibiotics (vancomycin, fidaxomicin), anti-inflammatory agents (mesalamine, sulfasalazine), corticosteroids (budesonide, prednisone), integrin receptor antagonists (vedolizumab), several semi-invasive procedures such as fecal transplant microbiota (FMT), aminosalicylates (5-ASA), treatment with tumor necrosis factor (TNF) blockers (adalimumab, golimumab), and immunomodulators (upadcitinib, tofacitinib). This leads us to establish how rCDI and its resistance to different treatments make this a challenge for the health system, both for hospitals and for outpatients, as well as how time-consuming each treatment is from the first intake of the drug until its total efficacy or until patients reach a dose-response and time-response to the disease. Accordingly, this case report and other similar cases reflect the need for randomized control trials or meta-analyses to establish therapeutic guidelines for cases of mdCDI in the near future.}, } @article {pmid37602197, year = {2023}, author = {Gao, XF and Wu, BB and Pan, YL and Zhou, SM and Zhang, M and You, YH and Cai, YP and Liang, Y}, title = {Gut microbiome biomarkers in adolescent obesity: a regional study.}, journal = {Health information science and systems}, volume = {11}, number = {1}, pages = {37}, pmid = {37602197}, issn = {2047-2501}, abstract = {PURPOSE: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome.

METHODS: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition.

RESULTS: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders.

CONCLUSIONS: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.}, } @article {pmid37602044, year = {2023}, author = {Jaramillo, AP and Awosusi, BL and Ayyub, J and Dabhi, KN and Gohil, NV and Tanveer, N and Hussein, S and Pingili, S and Makkena, VK}, title = {Effectiveness of Fecal Microbiota Transplantation Treatment in Patients With Recurrent Clostridium difficile Infection, Ulcerative Colitis, and Crohn's Disease: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42120}, pmid = {37602044}, issn = {2168-8184}, abstract = {Cronh's disease and ulcerative colitis (UC) are diseases with unknown etiologies that cause ongoing inflammation in the gastrointestinal system. Chron's disease causes immunological dysregulation, and UC causes intestinal harm due to immune reactions. According to our study, fecal microbiota transplantation (FMT) has many benefits in the treatment of inflammatory bowel disease (IBD) by restoring intestinal homeostasis and reducing clinical symptoms. In mildly symptomatic patients with UC, an FMT treatment combined with an anti-inflammatory diet can produce remission, which would then be followed by a diet that maintained the anti-inflammatory effects. The efficacy of FMT consists of preventing flares or the consequences of IBD. As a result, we must emphasize that more investigation should be done before developing a therapeutic procedure for FMT in IBD and its associated consequences.}, } @article {pmid37601998, year = {2023}, author = {Edupuganti, S and Yadav, D and Upadhyay, M and Benck, AR and Nika, A}, title = {A Rare Presentation of Myositis and Diffuse Alveolar Hemorrhage Associated With Disseminated Cryptococcus neoformans Infection.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42062}, pmid = {37601998}, issn = {2168-8184}, abstract = {Cryptococcosis is a fungal infection caused by species of the Cryptococcus genus which are commonly found in soil contaminated with bird feces, decaying wood, and tree hollows. It is usually seen in immunocompromised patients such as those with AIDS, with hematological malignancy, on immunosuppressive therapy, or after organ transplantation, and rare in immunocompetent hosts. The primary site of infection is usually the lung and the infection starts after inhalation of the pathogen and depending upon the host's immune response shows a different pattern of infection. Here we present a case report of a female in her late forties, who presented with two weeks of rash in her bilateral upper extremity, lower extremity, chest, and back along with arthralgia, myalgia, and proximal lower extremity weakness. Initial laboratory workup showed leukocytosis, elevated erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and serum aldolase level with normal creatinine kinase. Rheumatological workups including ANA, ANCA, RF, C3, and C4 were normal. Magnetic resonance imaging of the right femur showed hyperintensity of the thigh and proximal calf musculature suggestive of muscle edema. A punch biopsy from the rash showed dyskeratosis with mild perivascular neutrophilic infiltrate. Steroid therapy and rituximab were started with some improvement. However, the patient developed respiratory distress and diffuse alveolar hemorrhage. Bronchoscopy was done and bronchoalveolar lavage fluid grew Serratia and Candida. The patient improved with antibiotic and antifungal therapy. However, the patient again developed respiratory distress and a new diffuse alveolar hemorrhage. A repeat bronchoscopy was done and the new bronchoalveolar lavage grew Cryptococcus neoformans. Blood cultures also grew Cryptococcus neoformans. The patient was started on amphotericin B and flucytosine. The patient initially improved and was transferred to the rehabilitation unit but ultimately her course was complicated by multiple infections and intubations and she unfortunately passed away.}, } @article {pmid37600604, year = {2023}, author = {Busing, JD and Fouladi, F and Bulik-Sullivan, EC and Carroll, IM and Fodor, AA and Thomsen, KF and Gulati, AS and Nicholson, MR}, title = {Gut Microbial Changes Following Fecal Microbiota Transplantation for D-Lactic Acidosis in Two Children.}, journal = {JPGN reports}, volume = {4}, number = {3}, pages = {e319}, pmid = {37600604}, issn = {2691-171X}, abstract = {D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA.}, } @article {pmid37600095, year = {2022}, author = {Freidin, D and Zilka, N and Horesh, N and Saukhat, O and Ram, E and Tejman-Yarden, S}, title = {Using Augmented Reality for Intraoperative Guidance During Sacral Neuromodulation System Implantation.}, journal = {Annals of surgery open : perspectives of surgical history, education, and clinical approaches}, volume = {3}, number = {1}, pages = {e138}, pmid = {37600095}, issn = {2691-3593}, abstract = {OBJECTIVE: The purpose of this study was to examine the feasibility of using augmented reality during lead placement for sacral nerve stimulation (SNS).

METHODS: The study was a prospective case series performed in a single tertiary center. Patients with fecal incontinence or urinary retention eligible for SNS according to the American society of colon and rectal surgeon's guidelines were included. Each patient underwent a computerized tomography scan of the sacrum and pelvic floor before surgery; and a segmentation of the sacral bone, the skin, and three fiducial markers on the lower back was produced. Surgical planning included the design of an ideal virtual transmission tract leading to the S3 foramen using the most suitable location and needle trajectory for introducing the lead. During the surgical intervention, a needle was inserted into the S3 foramen using the aligned tract as visualized using the Microsoft HoloLens first generation head mounted unit.

RESULTS: Overall, 11 patients were included. Mean operative time was 43.8 minutes (range 25-81 minutes). All patients reported a significant reduction from the preoperative level of the mean postoperative Cleveland Clinic Incontinence Score (CCIS) assessed 2 weeks after the temporary SNS implant (CCIS preoperative 13.3, postoperative 8.5; CI -7.35 to -2.25; P < 0.01). The surgeons reported the imaging useful, allowing accurate and easier approach.

CONCLUSIONS: Intraoperative augmented reality imaging for needle application during SNS appears to be feasible, practical, and may be useful in additional procedures.}, } @article {pmid37599693, year = {2023}, author = {Wang, Y and Ni, Z and Li, J and Shao, Y and Yong, Y and Lv, W and Zhang, S and Fu, T and Chen, A}, title = {Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1203430}, pmid = {37599693}, issn = {2296-861X}, abstract = {INTRODUCTION: The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities.

METHODS: This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.

RESULTS: The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.

DISCUSSION: This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.}, } @article {pmid37599322, year = {2023}, author = {Salimi, A and Sepehr, A and Hejazifar, N and Talebi, M and Rohani, M and Pourshafie, MR}, title = {The Anti-Inflammatory Effect of a Probiotic Cocktail in Human Feces Induced-Mouse Model.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {37599322}, issn = {1573-2576}, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract due to altered interaction between the immune system and the gut microbiota. The aim of this study was to investigate the role of a probiotic cocktail in modulating immune dysregulation induced in mice. Mice were divided into 5 groups (n = 5/group), and inflammation was induced in two separate groups by fecal microbiota transplantation (FMT) from the stool of human with IBD and dextran sulfate sodium (DSS). In the other two groups, the cocktail of Lactobacillus spp. and Bifidobacterium spp. (10[8]CFU/kg/day) was administered daily for a total of 28days in addition to inducing inflammation. A group as a contcxsrol group received only water and food. The alteration of the selected genera of gut microbiota and the expression of some genes involved in the regulation of the inflammatory response were studied in the probiotic-treated and untreated groups by quantitative real-time PCR. The selected genera of gut microbiota of the FMT and DSS groups showed similar patterns on day 28 after each treatment. In the probiotic-treated groups, the population of the selected genera of gut microbiota normalized and the abundance of Firmicutes and Actinobacteria increased compared to the DSS and FMT groups. The expression of genes related to immune response and tight junctions was positively affected by the probiotic. Changes in the gut microbiota could influence the inflammatory status in the gut, and probiotics as a preventive or complementary treatment could improve the well-being of patients with inflammatory bowel disease symptoms.}, } @article {pmid37596429, year = {2023}, author = {Qiao, CM and Zhou, Y and Quan, W and Ma, XY and Zhao, LP and Shi, Y and Hong, H and Wu, J and Niu, GY and Chen, YN and Zhu, S and Cui, C and Zhao, WJ and Shen, YQ}, title = {Fecal Microbiota Transplantation from Aged Mice Render Recipient Mice Resistant to MPTP-Induced Nigrostriatal Degeneration Via a Neurogenesis-Dependent but Inflammation-Independent Manner.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {}, pmid = {37596429}, issn = {1878-7479}, support = {81771384//National Natural Science Foundation of China/ ; 81801276//National Natural Science Foundation of China/ ; 82171429//National Natural Science Foundation of China/ ; KYCX19_1893//Postgraduate Research and Practice Innovation Program of Jiangsu Province/ ; JUPH201801//Public Health Research Center at Jiangnan University/ ; JUSRP121063//Youth Foundation of Basic Research Program of Jiangnan University in 2021/ ; }, abstract = {Accumulating data support a crucial role of gut microbiota in Parkinson's disease (PD). However, gut microbiota vary with age and, thus, will affect PD in an age-dependent, but unknown manner. We examined the effects of fecal microbiota transplantation (FMT) pretreatment, using fecal microbiota from young (7 weeks) or aged mice (23 months), on MPTP-induced PD model. Motor function, pathological changes, striatal neurotransmitters, neuroinflammation, gut inflammation and gut permeability were examined. Gut microbiota composition and metabolites, namely short-chain fatty acids (SCFAs), were analyzed. Neurogenesis was also evaluated by measuring the number of doublecortin-positive (DCX[+]) neurons and Ki67-positive (Ki67[+]) cells in the hippocampus. Expression of Cd133 mRNA, a cellular stemness marker, in the hippocampus was also examined. Mice who received FMT from young mice showed MPTP-induced motor dysfunction, and reduction of striatal dopamine (DA), dopaminergic neurons and striatal tyrosine hydroxylase (TH) levels. Interestingly and unexpectedly, mice that received FMT from aged mice showed recovery of motor function and rescue of dopaminergic neurons and striatal 5-hydroxytryptamine (5-HT), as well as decreased DA metabolism after MPTP challenge. Further, they showed improved metabolic profiling and a decreased amount of fecal SCFAs. High-throughput sequencing revealed that FMT remarkably reshaped the gut microbiota of recipient mice. For instance, levels of genus Akkermansia and Candidatus Saccharimonas were elevated in fecal samples of recipient mice receiving aged microbiota (AM + MPTP mice) than YM + MPTP mice. Intriguingly, both young microbiota and aged microbiota had no effect on neuroinflammation, gut inflammation or gut permeability. Notably, AM + MPTP mice showed a marked increase in DCX[+] neurons, as well as Ki67[+] cells and Cd133 expression in the hippocampal dentate gyrus (DG) compared to YM + MPTP mice. These results suggest that FMT from aged mice augments neurogenesis, improves motor function and restores dopaminergic neurons and neurotransmitters in PD model mice, possibly through increasing neurogenesis.}, } @article {pmid37593952, year = {2023}, author = {Koneru, S and Thiruvadi, V and Ramesh, M}, title = {Gut microbiome and its clinical implications: exploring the key players in human health.}, journal = {Current opinion in infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/QCO.0000000000000958}, pmid = {37593952}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: The human gut harbors a diverse community of microorganisms known as the gut microbiota. Extensive research in recent years has shed light on the profound influence of the gut microbiome on human health and disease. This review aims to explore the role of the gut microbiome in various clinical conditions and highlight the emerging therapeutic potential of targeting the gut microbiota for disease management.

RECENT FINDINGS: Knowledge of the influence of gut microbiota on human physiology led to the development of various therapeutic possibilities such as fecal microbiota transplant (FMT), phage therapy, prebiotics, and probiotics. Recently, the U.S. FDA approved two FMT products for the treatment of recurrent Clostridioides difficile infection with ongoing research for the treatment of various disease conditions.

SUMMARY: Advancement in the knowledge of the association between gut microbiota and various disease processes has paved the way for novel therapeutics.}, } @article {pmid37585413, year = {2023}, author = {Li, C and Liu, Y and Liu, X and Bai, X and Jin, X and Xu, F and Chen, H and Zhang, Y and Vallee, I and Liu, M and Yang, Y}, title = {The gut microbiota contributes to changes in the host immune response induced by Trichinella spiralis.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {8}, pages = {e0011479}, pmid = {37585413}, issn = {1935-2735}, mesh = {Mice ; Animals ; *Trichinella spiralis ; *Trichinellosis/parasitology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Immunity ; }, abstract = {The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T. spiralis and the role of the gut microbiota in host immune defense against T. spiralis infection were investigated in our study. 16S rRNA sequencing analysis revealed that infection with T. spiralis can reduce the diversity of the gut microbiota and alter the structure of the gut microbiota during early infection, which was restored when the worm left the gut. Antibiotic treatment (ABX) and fecal bacterial transplantation (FMT) were used to investigate the role of the gut microbiota in the host expulsion response during infection with T. spiralis. We found that ABX mice had a higher burden of parasites, and the burden of parasites decreased after fecal bacterial transplantation. The results of flow cytometry and qPCR revealed that the disturbance of the gut microbiota affects the proportion of CD4+ T cells and the production of IL-4, which weakens Th2 responses and makes expulsion difficult. In addition, as the inflammatory response decreased with the changes of the microbiota, the Th1 response also decreased. The metabolomic results were in good agreement with these findings, as the levels of inflammatory metabolites such as ceramides were reduced in the ABX group. In general, T. spiralis infection can cause changes in the gut microbiota, and the presence or absence of microbes may also weaken intestinal inflammation and the expulsion of T. spiralis by affecting the immune response of the host.}, } @article {pmid37583860, year = {2023}, author = {Kriger-Sharabi, O and Malnick, SDH and Fisher, D}, title = {Manipulation of the intestinal microbiome-a slow journey to primetime.}, journal = {World journal of clinical cases}, volume = {11}, number = {21}, pages = {4975-4988}, pmid = {37583860}, issn = {2307-8960}, abstract = {The gut microbiota has important functions in the regulation of normal body functions. Alterations of the microbiota are being increasingly linked to various disease states. The microbiome has been manipulated via the administration of stool from animals or humans, for more than 1000 years. Currently, fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools. More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection (CDI). In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation, metabolic associated fatty liver disease (MAFLD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI, MAFLD, IBS and IBD.}, } @article {pmid37583034, year = {2023}, author = {Bae, GS and Jeon, ES and Son, HC and Kang, P and Lim, KS and Hwang, EH and Kim, G and Baek, SH and An, YJ and Shim, GY and Woo, YM and Kim, Y and Oh, T and Kim, SH and Hong, J and Koo, BS}, title = {Clostridium ventriculi in a cynomolgus monkey with acute gastric dilatation and rupture: A case report.}, journal = {Journal of medical primatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jmp.12668}, pmid = {37583034}, issn = {1600-0684}, support = {//The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021M3H9A2098600)./ ; }, abstract = {Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools. The monkey had undergone surgery previously. On necropsy, gastric dilatation and rupture demonstrated a tetrad arrangement on histopathologic examination. On 16S rRNA sequencing, a high population of Clostridium ventriculi was identified in the duodenum adjacent to stomach but not in the colon. This paper is the first report of Clostridium ventriculi infection in a cynomolgus macaque with acute gastric dilatation and rupture.}, } @article {pmid37581848, year = {2023}, author = {Dou, M and Chu, Y and Zhou, X and Wang, M and Li, X and Ma, R and Fan, Z and Zhao, X and Wang, W and Li, S and Lv, Y and Zhu, L}, title = {Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37581848}, issn = {1559-1182}, support = {31870334//National Natural Science Foundation of China/ ; }, abstract = {There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.}, } @article {pmid37580821, year = {2023}, author = {Shtossel, O and Turjeman, S and Riumin, A and Goldberg, MR and Elizur, A and Bekor, Y and Mor, H and Koren, O and Louzoun, Y}, title = {Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {181}, pmid = {37580821}, issn = {2049-2618}, support = {101001355//European Research Council Consolidator grant/ ; 870/20//ISF grant/ ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Treatment Outcome ; *Microbiota ; }, abstract = {BACKGROUND: Some microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT). FMT donor selection is currently based on donor phenotype, rather than the anticipated microbiota composition in the recipient and associated health benefits. However, the donor and post-transplant recipient conditions differ drastically. We here propose an algorithm to identify ideal donors and predict the expected outcome of FMT based on donor microbiome alone. We also demonstrate how to optimize FMT for different required outcomes.

RESULTS: We show, using multiple microbiome properties, that donor and post-transplant recipient microbiota differ widely and propose a tool to predict the recipient post-transplant condition (engraftment success and clinical outcome), using only the donors' microbiome and, when available, demographics for transplantations from humans to either mice or other humans (with or without antibiotic pre-treatment). We validated the predictor using a de novo FMT experiment highlighting the possibility of choosing transplants that optimize an array of required goals. We then extend the method to characterize a best-planned transplant (bacterial cocktail) by combining the predictor and a generative genetic algorithm (GA). We further show that a limited number of taxa is enough for an FMT to produce a desired microbiome or phenotype.

CONCLUSIONS: Off-the-shelf FMT requires recipient-independent optimized FMT selection. Such a transplant can be from an optimal donor or from a cultured set of microbes. We have here shown the feasibility of both types of manipulations in mouse and human recipients. Video Abstract.}, } @article {pmid37579688, year = {2023}, author = {Liu, Y and Zhou, Q and Ye, F and Yang, C and Jiang, H}, title = {Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization.}, journal = {Neoplasia (New York, N.Y.)}, volume = {43}, number = {}, pages = {100928}, doi = {10.1016/j.neo.2023.100928}, pmid = {37579688}, issn = {1476-5586}, abstract = {We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients' fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.}, } @article {pmid37577219, year = {2023}, author = {Tan, N and Lubel, J and Kemp, W and Roberts, S and Majeed, A}, title = {Current Therapeutics in Primary Sclerosing Cholangitis.}, journal = {Journal of clinical and translational hepatology}, volume = {11}, number = {5}, pages = {1267-1281}, pmid = {37577219}, issn = {2310-8819}, abstract = {Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.}, } @article {pmid37572993, year = {2023}, author = {Singh, A and Ashar, H and Ranjan, A}, title = {Age-dependent modulation of gut microbiome in response to tumor immunomodulation.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {112268}, doi = {10.1016/j.exger.2023.112268}, pmid = {37572993}, issn = {1873-6815}, abstract = {In-situ vaccination (ISV) utilizing nanoparticles (NPs) and therapeutic devices like focused ultrasound (FUS) can trigger immune-mediated killing of both treated and untreated cancer cells. However, the impact of confounding factors such as aging and gut microbiota composition on therapeutic outcomes remains poorly understood. In this study, we sequentially treated young mice (~8 weeks) and old mice (>18 months) with bilateral melanoma using FUS and calreticulin nanoparticles (CRT-NP) to enhance immunogenic cell death. The combination of CRT-NP and FUS (CFUS) demonstrated greater efficacy in inducing regression of treated and untreated tumors in young mice compared to old mice. The diminished effectiveness in older mice was associated with significant differences in gut microbiome composition, characterized by alterations in bacterial species and splenic immune cells. Specifically, young mice exposed to CFUS exhibited higher abundance of Bacteroidetes and Verrucomicrobia, which was not observed in the aged cohorts. Turicibacter, Anaerotruncus, and Ruminiclostridium demonstrated negative correlations with CD8+ T cells but positive correlations with CD4+ T cells and MDSC cells in both age groups. Taxon set enrichment analysis revealed 58 significantly enriched host gene targets in the young cluster compared to only 11 in the aged cluster. These findings highlight the relationship between ISV treatment efficacy and gut microbiome composition, suggesting that interventions such as diet modification, probiotics, or fecal microbiota transplantation may hold potential as therapeutic strategies to enhance immune responses against solid tumors.}, } @article {pmid37572864, year = {2023}, author = {Mansoor, AE and O'Neil, CA and Kwon, JH}, title = {The role of microbiome-based therapeutics for antimicrobial-resistant organism colonization.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102772}, doi = {10.1016/j.anaerobe.2023.102772}, pmid = {37572864}, issn = {1095-8274}, abstract = {The gut is host to a diverse array of microbiota that constitute a complex ecological system crucial to human physiology. Disruptors to the normal host microbiota, such as antimicrobials, can cause a loss of species diversity in the gut, reducing its ability to resist colonization by invading pathogens, and potentially leading to colonization with antimicrobial resistant organisms (AROs). ARO negatively impact gut health by disrupting the usual heterogeneity of gut microbiota and have the potential to cause systemic disease. In recent years, fecal microbiota transplantation (FMT) has been increasingly explored in the management of specific disease states such as Clostridioides difficile infection (CDI). Promising data from management of CDI has led to considerable interest in understanding the role of therapeutics to restore the gut microbiota to a healthy state. This review aims to discuss key studies that highlight the current landscape, and explore existing clinical evidence, for the use of FMT and microbiome-based therapeutics in combating intestinal colonization with ARO. We also explore potential future directions of such therapeutics and discuss unaddressed needs in this field that merit further investigation.}, } @article {pmid37571277, year = {2023}, author = {Wu, X and Li, P and Wang, W and Xu, J and Ai, R and Wen, Q and Cui, B and Zhang, F}, title = {The Underlying Changes in Serum Metabolic Profiles and Efficacy Prediction in Patients with Extensive Ulcerative Colitis Undergoing Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {15}, number = {15}, pages = {}, pmid = {37571277}, issn = {2072-6643}, support = {82170563//National Natural Science Foundation of China/ ; 2021YFA0717004//National Key R&D Program of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/etiology ; Treatment Outcome ; Metabolome ; Metabolomics ; Feces ; }, abstract = {(1) Background: Fecal microbiota transplantation (FMT) is an effective treatment for ulcerative colitis (UC). Metabolomic techniques would assist physicians in clinical decision-making. (2) Methods: Patients with active UC undergoing FMT were enrolled in the study and monitored for 3 months. We explored short-term changes in the serum metabolic signatures of groups and the association between baseline serum metabolomic profiles and patient outcomes. (3) Results: Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT. The top two significantly altered pathways in the response group were vitamin B6 metabolism and aminoacyl-tRNA biosynthesis. Both the remission and response groups exhibited an altered and enriched pathway for the biosynthesis of primary bile acid. We found a clear separation between the remission and non-remission groups at baseline, characterized by the higher levels of glycerophosphocholines, glycerophospholipids, and glycerophosphoethanolamines in the remission group. A random forest (RF) classifier was constructed with 20 metabolic markers selected by the Boruta method to predict clinical remission 3 months post-FMT, with an area under the curve of 0.963. (4) Conclusions: FMT effectively induced a response in patients with active UC, with metabolites partially improving post-FMT in the responsive group. A promising role of serum metabolites in the non-invasive prediction of FMT efficacy for UC demonstrated the value of metabolome-informed FMT in managing UC.}, } @article {pmid37569381, year = {2023}, author = {Mingaila, J and Atzeni, A and Burokas, A}, title = {A Comparison of Methods of Gut Microbiota Transplantation for Preclinical Studies.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, doi = {10.3390/ijms241512005}, pmid = {37569381}, issn = {1422-0067}, support = {No. 01.2.2-LMT-K-718-02-0014//European Regional Development Fund/ ; }, abstract = {The experimental details reported in preclinical fecal microbiota transplantation (FMT) protocols are highly inconsistent, variable, and/or incomplete. We therefore evaluated FMT from a human donor to antibiotic-induced microbial-depleted mice by exploring the effects of six techniques based on antibiotic (AB) or antibiotic + antimycotic (AB + T) gut decontamination, different administration routes, and different dosing intervals on the gut microbial population, assessed using 16S and 18S sequencing. In addition, we explored the effectiveness of FMT in terms of inflammation, physiological, and behavioral outcomes. Our results showed that intrarectal FMT at low dosing intervals better preserved the donor's gut bacterial community at genus level. Furthermore, we showed a lower abundance of several genera of fungi in animals treated with AB + T. In addition, we observed that AB + T gut decontamination followed by per os FMT, once every 3 days, affected behavioral parameters when compared to other FMT techniques. Accordingly, the same FMT groups that showed an association with some of the behavioral tests were also related to specific gut fungal genera, suggesting a possible mediation. Our findings may be useful for optimizing the practice of FMT and also in terms of donor microbiota preservation. This information may help to improve the reproducibility and reliability of FMT studies.}, } @article {pmid37569349, year = {2023}, author = {Bendriss, G and MacDonald, R and McVeigh, C}, title = {Microbial Reprogramming in Obsessive-Compulsive Disorders: A Review of Gut-Brain Communication and Emerging Evidence.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, doi = {10.3390/ijms241511978}, pmid = {37569349}, issn = {1422-0067}, abstract = {Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.}, } @article {pmid37569261, year = {2023}, author = {Cao, Z and Ling, X and Sun, P and Zheng, X and Zhang, H and Zhong, J and Yin, W and Fan, K and Sun, Y and Li, H and Sun, N}, title = {Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, doi = {10.3390/ijms241511878}, pmid = {37569261}, issn = {1422-0067}, support = {32172904//National Natural Science Foundation of China/ ; 2022YFD1801101//National Key Research and Development Program/ ; 202102140601019//Key Research and Development Plan of Shanxi Province/ ; 202204051001021//The special fund for Science and Technology Innovation Teams of Shanxi Province/ ; No. 20211331-16, No. 20211331-13//Shanxi "1331 Project"/ ; None//the earmarked fund for Modern Agro-industry Technology Research System/ ; }, abstract = {Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1β mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1β mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1β mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1β mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.}, } @article {pmid37567034, year = {2023}, author = {Dai, Y and Shen, Z and Khachatryan, LG and Vadiyan, DE and Karampoor, S and Mirzaei, R}, title = {Unraveling mechanistic insights into the role of microbiome in neurogenic hypertension: A comprehensive review.}, journal = {Pathology, research and practice}, volume = {249}, number = {}, pages = {154740}, doi = {10.1016/j.prp.2023.154740}, pmid = {37567034}, issn = {1618-0631}, abstract = {Neurogenic hypertension, a complex and multifactorial cardiovascular disorder, is known to be influenced by various genetic, environmental, and lifestyle factors. In recent years, there has been growing interest in the role of the gut microbiome in hypertension pathogenesis. The bidirectional communication between the gut microbiota and the central nervous system, known as the microbiota-gut-brain axis, has emerged as a crucial mechanism through which the gut microbiota exerts its influence on neuroinflammation, immune responses, and blood pressure regulation. Recent studies have shown how the microbiome has a substantial impact on a variety of physiological functions, such as cardiovascular health. The increased sympathetic activity to the gut may cause microbial dysbiosis, increased permeability of the gut, and increased inflammatory reactions by altering a number of intestinal bacteria producing short-chain fatty acids (SCFAs) and the concentrations of lipopolysaccharide (LPS) in the plasma. Collectively, these microbial metabolic and structural compounds stimulate sympathetic stimulation, which may be an important stage in the onset of hypertension. The result is an upsurge in peripheral and central inflammatory response. In addition, it has recently been shown that a link between the immune system and the gut microbiota might play a significant role in hypertension. The therapeutic implications of the gut microbiome including probiotic usage, prebiotics, dietary modifications, and fecal microbiota transplantation in neurogenic hypertension have also been found. A large body of research suggests that probiotic supplementation might help reduce chronic inflammation and hypertension that have an association with dysbiosis in the gut microbiota. Overall, this review sheds light on the intricate interplay between the gut microbiome and neurogenic hypertension, providing valuable insights for both researchers and clinicians. As our knowledge of the microbiome's role in hypertension expands, novel therapeutic strategies and diagnostic biomarkers may pave the way for more effective management and prevention of this prevalent cardiovascular disorder. Exploring the potential of the microbiome in hypertension offers an exciting avenue for future research and offers opportunities for precision medicine and improved patient care.}, } @article {pmid37566569, year = {2023}, author = {Hong, Y and Dong, H and Zhou, J and Luo, Y and Yuan, MM and Zhan, JF and Liu, YL and Xia, JY and Zhang, L}, title = {Aged gut microbiota contribute to different changes in antioxidant defense in the heart and liver after transfer to germ-free mice.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0289892}, pmid = {37566569}, issn = {1932-6203}, abstract = {Age-associated impairment in antioxidant defense is an important cause of oxidative stress, and elderly individuals are usually associated with gut microbiota (GM) changes. Studies have suggested a potential relationship between the GM and changes in antioxidant defense in aging animals. Direct evidence regarding the impact of aging-associated shifts in GM on the antioxidant defense is lacking. The heart is a kind of postmitotic tissue, which is more prone to oxidative stress than the liver (mitotic tissue). To test and compare the influence of an aged GM on antioxidant defense changes in the heart and liver of the host, in this study, GM from young adolescent (5 weeks) or aged (20 months) mice was transferred to young adolescent (5 weeks) germ-free (GF) mice (N = 5 per group) by fecal microbiota transplantation (FMT). Four weeks after the first FMT was performed, fecal samples were collected for 16S rRNA sequencing. Blood, heart and liver samples were harvested for oxidative stress marker and antioxidant defense analysis. The results showed that mice that received young or aged microbiota showed clear differences in GM composition and diversity. Mice that received aged microbiota had a lower ratio of Bacteroidetes/Firmicutes in GM at the phylum level and an increased relative abundance of four GM genera: Akkermansia, Dubosiella, Alistipes and Rikenellaceae_RC9_gut_group. In addition, GM α-diversity scores based on the Shannon index and Simpson index were significantly higher in aged GM-treated mice. Oxidative stress marker and antioxidant defense tests showed that FMT from aged donors did not have a significant influence on malondialdehyde content in serum, heart and liver. However, the capacity of anti-hydroxyl radicals in the heart and liver, as well as the capacity of anti-superoxide anions in the liver, were significantly increased in mice with aged microbiota. FMT from aged donors increased the activities of Cu/Zn superoxide SOD (Cu/Zn-SOD), catalase (CAT) and glutathione-S-transferase in the heart, as well as the activity of Cu/Zn-SOD in the liver. Positive correlations were found between Cu/Zn-SOD activity and radical scavenging capacities. On the other hand, glutathione reductase activity and glutathione content in the liver were decreased in mice that received aged GM. These findings suggest that aged GM transplantation from hosts is sufficient to influence the antioxidant defense system of young adolescent recipients in an organ-dependent manner, which highlights the importance of the GM in the aging process of the host.}, } @article {pmid37562707, year = {2023}, author = {Zhang, Z and Li, Q and Zhang, S and Liu, Y and Lu, G and Wen, Q and Cui, B and Zhang, F and Zhang, F}, title = {Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {110839}, doi = {10.1016/j.pnpbp.2023.110839}, pmid = {37562707}, issn = {1878-4216}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS.

METHODS: This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT.

RESULTS: Seventy-three patients with IBS were included in the study. Sleep quality (Z = -4.221, P < 0.001), anxiety (Z = -4.775, P < 0.001), depression (Z = -4.610, P < 0.001), gastrointestinal symptoms (Z = -5.364, P < 0.001), and IBS severity (Z = -6.468, P < 0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P < 0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI = 1.017-4.673]; P = 0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z = -1.990, P = 0.047) and IBS severity (Z = -2.486, P = 0.013) compared with patients without sleep improvement.

CONCLUSION: This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.}, } @article {pmid37560802, year = {2023}, author = {Shirley, DA and Tornel, W and Warren, CA and Moonah, S}, title = {Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy.}, journal = {Pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1542/peds.2023-062307}, pmid = {37560802}, issn = {1098-4275}, abstract = {Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.}, } @article {pmid37558058, year = {2023}, author = {Arditi, Z and Bunyavanich, S}, title = {Commensal Collaborations: Food Allergy and the Microbiome.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2023.08.001}, pmid = {37558058}, issn = {1097-6825}, } @article {pmid37558018, year = {2023}, author = {Zhou, Y and Jia, Y and Xu, N and Tang, L and Chang, Y}, title = {Auricularia auricula-judae (Bull.) polysaccharides improve obesity in mice by regulating gut microbiota and TLR4/JNK signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {126172}, doi = {10.1016/j.ijbiomac.2023.126172}, pmid = {37558018}, issn = {1879-0003}, abstract = {Obesity has emerged as a crucial factor impacting people's lives, and gut microbiota disorders contribute to its development and progression. Auricularia auricula-judae (Bull.) polysaccharides (AAPs), a traditional functional food in Asia, exhibit potential anti-obesity effects. However, the specific mechanism still needs to be further confirmed. This study investigated the beneficial effects and specific mechanisms of AAPs on obesity. Firstly, AAPs showed significant improvements in overweight, insulin resistance, glucose and lipid metabolism disorders, and liver damage in obese mice. Additionally, AAPs ameliorated gut microbiota disorders, promoting the proliferation of beneficial bacteria like Lactobacillus and Roseburia, resulting in increased levels of SCFAs, folate, and cobalamin. Simultaneously, AAPs inhibited the growth of harmful bacteria, thereby protecting intestinal barrier function, improving endotoxemia, and decreasing the levels of inflammatory factors such as TNF-α and IL-6. Furthermore, AAPs can inhibit the TLR4/JNK signaling pathway while promoting the activation of AKT and AMPK. Importantly, our study underscored the pivotal role of gut microbiota in the anti-obesity effects of AAPs, as evidenced by fecal microbiota transplantation experiments. In conclusion, our findings elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion the anti-obesity potential of AAPs.}, } @article {pmid37557963, year = {2023}, author = {Angela Guzzardi, M and La Rosa, F and Granziera, F and Panetta, D and Pardo-Tendero, M and Barone, M and Turroni, S and Faita, F and Kusmic, C and Brigidi, P and Monleon, D and Iozzo, P}, title = {Gut-derived metabolites mediating cognitive development in 5-year-old children: early-life transplant in mice has lasting effects throughout adulthood.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2023.08.009}, pmid = {37557963}, issn = {1090-2139}, abstract = {The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN-PISAC cohort, including 90 general population families with infants, 42/48 females/males, born in 2011-2014) were transplanted (FMT) into C57BL/6 germ-free mice. Children and recipient mice were stratified by cognitive phenotype, or based on protective metabolites. Food frequency questionnaires were obtained in children. Cognitive measurements in mice included five Y-maze tests until 23 weeks post-FMT, and (at 23 weeks) PET-CT for brain metabolism and radiodensity, and ultrasound-based carotid vascular indices. Children (faeces, urine) and mice (faeces, plasma) metabolome was measured by 1H-NMR spectroscopy, and the faecal microbiota was profiled in mice by 16S rRNA amplicon sequencing. Cognitive scores of children and recipient mice were correlated. FMT-dependent modifications of brain metabolism were observed. Mice receiving FMT from high-cognitive or protective metabolite-enriched children developed superior cognitive-behavioural performance. A panel of metabolites, namely xanthine, hypoxanthine, formate, mannose, tyrosine, phenylalanine, glutamine, was found to mediate the gut-cognitive axis in donor children and recipient mice. Vascular indices partially explained the metabolite-to-phenotype relationships. Children's consumption of legumes, whole-milk yogurt and eggs, and intake of iron, zinc and vitamin D appeared to support protective gut metabolites. Overall, metabolites involved in inflammation, purine metabolism and neurotransmitter synthesis mediate the gut-cognitive axis, and holds promise for screening. The related dietary and nutritional findings offer leads to microbiota-targeted interventions for cognitive protection, with long-lasting effects.}, } @article {pmid37555952, year = {2023}, author = {Benešová, I and Křížová, Ľ and Kverka, M}, title = {Microbiota as the unifying factor behind the hallmarks of cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37555952}, issn = {1432-1335}, support = {NV19-03-00179//Agentura Pro Zdravotnický Výzkum České Republiky/ ; LQ200202105//Mikrobiologický Ústav, Akademie Věd České Republiky/ ; }, abstract = {The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.}, } @article {pmid37554826, year = {2023}, author = {Chen, Y and Chai, H and Li, Z and Liu, B and Tan, M and Li, S and Ma, Y}, title = {Gut microbiota and their metabolite profiles following peripheral nerve xenotransplantation.}, journal = {Heliyon}, volume = {9}, number = {8}, pages = {e18529}, pmid = {37554826}, issn = {2405-8440}, abstract = {BACKGROUND: Intestinal pathogens are associated with xenotransplantation tolerance and rejection. However, changes in the gut microbiota in patients who have undergone peripheral nerve xenotransplantation and their association with immune rejection have not yet been reported.

OBJECTIVE: We aimed to explore intestinal microbes and their metabolites at different time points after peripheral nerve transplantation to provide new insight into improving transplant tolerance.

METHODS: A peripheral nerve xenotransplantation model was constructed by suturing the segmented nerves of Sprague Dawley rats to those of C57 male mice using xenotransplantation nerve bridging. Fecal samples and intestinal contents were collected at three time points: before surgery (Pre group; n = 10), 1 month after transplantation (Pos1 m group; n = 10), and 3 months after transplantation (Pos3 m group; n = 10) for 16S DNA sequencing and nontargeted metabolome detection.

RESULTS: Alpha diversity results suggested that species diversity was significantly downregulated after peripheral nerve xenotransplantation. There were six gut flora genera with significantly different expression levels after xenotransplantation: four were downregulated and two were upregulated. A comparison of the Pre vs. Pos1 m groups and the Pos1 m vs. Pos3 m groups revealed that the most significant differentially expressed Kyoto Encyclopedia of Genes and Genomes metabolite pathways were involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine metabolism. Metabolites with a strong relationship to the differentially expressed microbial flora were identified.

CONCLUSION: Our study found lower gut microbiome diversity, with increased short-chain fatty acid (SCFA)-producing and sulfate-reducing bacteria at 1 month post peripheral nerve xenotransplantation, and these were decreased at 3 months post-transplantation. The identification of specific bacterial metabolites is essential for recognizing potential diagnostic markers of xenotransplantation rejection or characterizing therapeutic targets to prevent post-transplant infection.}, } @article {pmid37554593, year = {2023}, author = {Sadagopan, A and Mahmoud, A and Begg, M and Tarhuni, M and Fotso, M and Gonzalez, NA and Sanivarapu, RR and Osman, U and Latha Kumar, A and Mohammed, L}, title = {Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e41559}, pmid = {37554593}, issn = {2168-8184}, abstract = {The gut microbiota has been studied and continues to be a developing area in the pathognomic development of metabolic diseases like diabetes. Treatment with diet changes, the addition of supplements like prebiotics/probiotics, and the impact of fecal microbial transplantation can be correlated to targeting changes in dysbiosis. Understanding the impacts of various anti-hyperglycemic agents such as metformin and the implications of post-bariatric surgery on the gut microbiota diversity has emerged. These areas of study are crucial to understanding the pathognomic aspects of diabetes disease progression at the microbial level of metabolic and inflammatory mechanisms, which may give more insight into focusing on the role of diet prebiotic/probiotic supplements as potential forms of prospective management in diabetes and the development of more agents that target gut microbiota, which harbors low-grade inflammation. Intestinal dysbiosis was consistently observed in the mechanism of gut microbial change in diabetic individuals, contributing to reduced insulin sensitivity and poor glycemic control. This systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 checklist. We performed a literature search using the PubMed, Google Scholar and Science Direct databases in accordance with the eligibility criteria and ultimately selected 14 articles for final analysis. The Scale for the Assessment of Narrative Review Articles (SANRA) and the PRISMA 2020 checklist were used to assess the quality of selected articles for cross-sectional studies, traditional literature reviews, and systematic reviews, respectively. We collected papers from 2012 to 2022 for this review. We gathered articles from databases, such as this study, which show there is a strong connection between microbiota and diabetes that appears to exist. The objective is to assess and identify any dietary and therapeutic agents that may alter the microbiota and potentially target and modulate insulin sensitivity. This review article will discuss the pathophysiological effects of gut microbiota in diabetes management and the impact of various gut biodiversity therapeutics that can aid in reversing insulin sensitivity.}, } @article {pmid37554355, year = {2023}, author = {Kwak, MJ and Kim, SH and Kim, HH and Tanpure, R and Kim, JI and Jeon, BH and Park, HK}, title = {Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1238005}, pmid = {37554355}, issn = {2235-2988}, abstract = {Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).}, } @article {pmid37554279, year = {2023}, author = {Chen, PP and Zhang, JX and Li, XQ and Li, L and Wu, QY and Liu, L and Wang, GH and Ruan, XZ and Ma, KL}, title = {Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease.}, journal = {Theranostics}, volume = {13}, number = {12}, pages = {3988-4003}, pmid = {37554279}, issn = {1838-7640}, abstract = {Rationale: Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease (DKD). However, its underlying mechanism is largely unknown. This study aims at investigating the role of gut microbiota-derived outer membrane vesicles (OMVs) in tubulointerstitial inflammation in DKD. Methods: Gut microbiota in diabetes mellitus rats was manipulated by microbiota depletion and fecal microbiota transplantation to explore its role in tubulointerstitial inflammation. To check the direct effects of OMVs, fecal bacterial extracellular vesicles (fBEVs) were administrated to mice orally and HK-2 cells in vitro. For mechanistic investigations, HK-2 cells were treated with small interfering RNA against caspase-4 and fBEVs pre-neutralized by polymyxin B. Results: By performing gut microbiota manipulation, it was confirmed that gut microbiota mediated tubulointerstitial inflammation in DKD. In diabetic rats, gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium. Diabetic fBEVs directly administered by gavage translocated into tubular epithelial cells and induced tubulointerstitial inflammation and kidney injury. In vitro, OMVs were internalized through various endocytic pathways and triggered cellular inflammatory response. Mechanistically, it was revealed that OMVs-derived lipopolysaccharide induced tubular inflammation, which was mediated by the activation of the caspase-11 pathway. Conclusions: Increased OMVs due to dysbiosis translocated through leaky gut barrier into distant tubulointerstitium and induced cellular inflammation and renal tubulointerstitial injury in DKD. These findings enrich the mechanism understanding of how gut microbiota and its releasing OMVs influence the development and progression of kidney disease.}, } @article {pmid37553783, year = {2023}, author = {El Jurdi, N and Holtan, SG and Hoeschen, A and Velguth, J and Hillmann, B and Betts, BC and MacMillan, ML and Weisdorf, DJ and Khoruts, A and Rashidi, A and Shields-Cutler, R}, title = {Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease.}, journal = {British journal of haematology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bjh.19016}, pmid = {37553783}, issn = {1365-2141}, support = {//UMN Grant-in-Aid/ ; //Chainbreaker/ ; //BRAINS/ ; }, abstract = {The role of the gastrointestinal microbiome in predisposing to chronic graft-versus-host disease (cGVHD), an immune-mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post-HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre-transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post-engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short-chain fatty acid metabolism were enriched in cGVHD patient microbiomes: β-oxidation and acyl-CoA synthesis, and γ-aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.}, } @article {pmid37550190, year = {2023}, author = {Zheng, YY and Yang, XT and Lin, GQ and Bian, MR and Si, YJ and Zhang, XX and Zhang, YM and Wu, DP}, title = {[Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {44}, number = {5}, pages = {401-407}, doi = {10.3760/cma.j.issn.0253-2727.2023.05.008}, pmid = {37550190}, issn = {0253-2727}, support = {M2020058//General Project of Medical Scientific Research of Jiangsu Provincial Health Commission/ ; SBK202003003//Opening Project of Sample Bank of Biological Resources of Key Diseases in Jiangsu Province/ ; XZSYSKF2020038, XZSYSKF2021026//Opening Project of Jiangsu Key Laboratory/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; Treatment Outcome ; *Graft vs Host Disease/therapy/diagnosis/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Steroids ; }, abstract = {Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.}, } @article {pmid37549868, year = {2023}, author = {Zong, X and Zhang, H and Zhu, L and C Deehan, E and Fu, J and Wang, Y and Jin, M}, title = {Auricularia auricula polysaccharides attenuate obesity in mice through gut commensal Papillibacter cinnamivorans.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2023.08.003}, pmid = {37549868}, issn = {2090-1224}, abstract = {INTRODUCTION: Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood.

METHODS: The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling.

RESULTS: High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans, a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner.

CONCLUSION: Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.}, } @article {pmid37549451, year = {2023}, author = {Chen, H and Wang, C and Bai, J and Song, J and Bu, L and Liang, M and Suo, H}, title = {Targeting microbiota to alleviate the harm caused by sleep deprivation.}, journal = {Microbiological research}, volume = {275}, number = {}, pages = {127467}, doi = {10.1016/j.micres.2023.127467}, pmid = {37549451}, issn = {1618-0623}, abstract = {Sleep deprivation has become a common health hazard, affecting 37-58% of the population and promoting the occurrence and development of many diseases. To date, effective treatment strategies are still elusive. Accumulating evidence indicates that modulating the intestinal microbiota harbors significant potential for alleviating the deleterious impacts of sleep deprivation. This paper first reviews the effects of sleep deprivation on gastrointestinal diseases, metabolic diseases, and neuropsychiatric diseases, discussing its specific mechanisms of influence. We then focus on summarizing existing interventions, including probiotics, melatonin, prebiotics, diet, and fecal microbiota transplantation (FMT). Finally, we have discussed the advantages and limitations of each strategy. Compared with other strategies, probiotics showed a high potential in alleviating sleep deprivation-related hazards due to their reduced risk and high security. We suggest that future research should focus on the specific mechanisms by which probiotics mitigate the harms of sleep deprivation, such insights may unveil novel pathways for treating diseases exacerbated by insufficient sleep.}, } @article {pmid37549387, year = {2023}, author = {Kanjee, Z and Allegretti, JR and Alonso, CD and Burns, RB}, title = {How Would You Manage This Patient With Clostridioides difficile Infection? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/M23-0754}, pmid = {37549387}, issn = {1539-3704}, abstract = {The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.}, } @article {pmid37548864, year = {2023}, author = {Philips, CA and Ahamed, R and Abduljaleel, JK and Rajesh, S and Tharakan, A and Augustine, P}, title = {Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {37548864}, issn = {0975-0711}, abstract = {Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.}, } @article {pmid37546903, year = {2023}, author = {Shrode, RL and Ollberding, NJ and Mangalam, AK}, title = {Looking at the Full Picture: Utilizing Topic Modeling to Determine Disease-Associated Microbiome Communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.07.21.549984}, pmid = {37546903}, abstract = {UNLABELLED: The microbiome is a complex micro-ecosystem that provides the host with pathogen defense, food metabolism, and other vital processes. Alterations of the microbiome (dysbiosis) have been linked with a number of diseases such as cancers, multiple sclerosis (MS), Alzheimer's disease, etc. Generally, differential abundance testing between the healthy and patient groups is performed to identify important bacteria (enriched or depleted in one group). However, simply providing a singular species of bacteria to an individual lacking that species for health improvement has not been as successful as fecal matter transplant (FMT) therapy. Interestingly, FMT therapy transfers the entire gut microbiome of a healthy (or mixture of) individual to an individual with a disease. FMTs do, however, have limited success, possibly due to concerns that not all bacteria in the community may be responsible for the healthy phenotype. Therefore, it is important to identify the community of microorganisms linked to the health as well as the disease state of the host. Here we applied topic modeling, a natural language processing tool, to assess latent interactions occurring among microbes; thus, providing a representation of the community of bacteria relevant to healthy vs. disease state. Specifically, we utilized our previously published data that studied the gut microbiome of patients with relapsing-remitting MS (RRMS), a neurodegenerative autoimmune disease that has been linked to a variety of factors, including a dysbiotic gut microbiome. With topic modeling we identified communities of bacteria associated with RRMS, including genera previously discovered, but also other taxa that would have been overlooked simply with differential abundance testing. Our work shows that topic modeling can be a useful tool for analyzing the microbiome in dysbiosis and that it could be considered along with the commonly utilized differential abundance tests to better understand the role of the gut microbiome in health and disease.

AUTHOR SUMMARY: Trillion of bacteria (microbiome) living in and on the human body play an important role in keeping us healthy and an alteration in their composition has been linked to multiple diseases such as cancers, multiple sclerosis (MS), and Alzheimer's. Identifying specific bacteria for targeted therapies is crucial, however studying individual bacteria fails to capture their interactions within the microbial community. The relative success of fecal matter transplants (FMTs) from healthy individual(s) to patients and the failure of individual bacterial therapy suggests the importance of the microbiome community in health. Therefore, there is a need to develop tools to identify the communities of microbes making up the healthy and disease state microbiome. Here we applied topic modeling, a natural language processing tool, to identify microbial communities associated with relapsing-remitting MS (RRMS). Specifically, we show the advantage of topic modeling in identifying the bacterial community structure of RRMS patients, which includes previously reported bacteria linked to RRMS but also otherwise overlooked bacteria. These results reveal that integrating topic modeling with traditional approaches improves the understanding of the microbiome in RRMS and it could be employed with other diseases that are known to have an altered microbiome.}, } @article {pmid37546803, year = {2023}, author = {Ghosh, S and Erickson, D and Chua, MJ and Collins, J and Jala, VR}, title = {The microbial metabolite Urolithin A reduces C. difficile toxin expression and repairs toxin-induced epithelial damage.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.07.24.550342}, pmid = {37546803}, abstract = {UNLABELLED: Clostridioides difficile is a gram-positive, anaerobic, spore-forming bacterium that is responsible for antibiotic-associated pseudomembranous colitis. Clostridioides difficile infection (CDI) symptoms can range from diarrhea to life-threatening colon damage. Toxins produced by C. difficile (TcdA and TcdB) cause intestinal epithelial injury and lead to severe gut barrier dysfunction, stem cell damage, and impaired regeneration of the gut epithelium. Current treatment options for intestinal repair are limited. In this study, we demonstrate that treatment with the microbial metabolite urolithin A (UroA) attenuates CDI-induced adverse effects on the colon epithelium in a preclinical model of CDI-induced colitis. Moreover, our analysis suggests that UroA treatment protects against C. difficile- induced inflammation, disruption of gut barrier integrity, and intestinal tight junction proteins in the colon of CDI mice. Importantly, UroA treatment significantly reduced the expression and release of toxins from C. difficile , without inducing bacterial cell death. These results indicate the direct regulatory effects of UroA on bacterial gene regulation. Overall, our findings reveal a novel aspect of UroA activities, as it appears to act at both the bacterial and host levels to protect against CDI-induced colitis pathogenesis. This research sheds light on a promising avenue for the development of novel treatments for C. difficile infection.

IMPORTANCE: Therapy for C. difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation (FMT). However, these treatments have several drawbacks, including the loss of colonization resistance, promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite Urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.}, } @article {pmid37545638, year = {2023}, author = {Maslennikov, R and Alieva, A and Poluektova, E and Zharikov, Y and Suslov, A and Letyagina, Y and Vasileva, E and Levshina, A and Kozlov, E and Ivashkin, V}, title = {Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.}, journal = {World journal of gastroenterology}, volume = {29}, number = {27}, pages = {4236-4251}, pmid = {37545638}, issn = {2219-2840}, abstract = {Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.}, } @article {pmid37545398, year = {2023}, author = {Huang, W and Chen, H and He, Q and Xie, W and Peng, Z and Ma, Q and Huang, Q and Chen, Z and Liu, Y}, title = {Nobiletin protects against ferroptosis to alleviate sepsis-associated acute liver injury by modulating the gut microbiota.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo01684f}, pmid = {37545398}, issn = {2042-650X}, abstract = {Nobiletin (NOB), a plant-based polymethoxyflavone, is a promising protective agent against sepsis; yet the mechanisms were not fully elucidated. The gut microbiota is found to be strongly associated with sepsis-associated acute liver injury (SALI). Here, our study aimed to evaluate the protective effect of NOB on SALI and explore the underlying molecular mechanisms. Cecal ligation and puncture (CLP) was used to induce SALI in mice. NOB was administered by gavage for 7 days before CLP induction. The 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) were performed to verify the function of the gut microbiota. The markers of ferroptosis, inflammation, gut microbiota composition, and liver injury were determined. NOB administration significantly alleviated hepatic ferroptosis and inflammation in septic mice. Meanwhile, NOB upregulated the expression levels of nuclear factor E2-related factor 2 (Nrf2) and its downstream protein heme oxygenase-1 (HO-1). The protective effect of NOB administration against ferroptosis in SALI mice was reversed by the Nrf2 inhibitor ML385. Additionally, increased abundances of Ligilactobacillus, Akkermansia, and Lactobacillus, and decreased abundances of Dubosiella and Bacteroides in the gut were observed under NOB administration, suggesting that NOB might modulate the gut microbiota composition of septic mice. Furthermore, gut microbiota ablation by antibiotic treatment partly reversed the protective effects of NOB on sepsis. FMT also confirmed that NOB inhibited ferroptosis and activated Nrf2 signalling in SALI mice by modulating the gut microbiota. These results revealed that, by modulating the gut microbiota, NOB attenuated ferroptosis in septic liver injury through upregulating Nrf2-Gpx4. Our findings provide novel insights into microbiome-based therapeutic approaches for sepsis.}, } @article {pmid37542273, year = {2023}, author = {Weng, S and Huang, L and Cai, B and He, L and Wen, S and Li, J and Zhong, Z and Zhang, H and Huang, C and Yang, Y and Jiang, Q and Liu, F}, title = {Astragaloside IV ameliorates experimental autoimmune myasthenia gravis by regulating CD4 + T cells and altering gut microbiota.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {97}, pmid = {37542273}, issn = {1749-8546}, support = {81904133//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2019QN28//First Affiliated Hospital of Zhengzhou University/ ; 202102080136//Guangzhou Municipal Science and Technology Project/ ; 2021XK18//Collaborative Innovation Center for Modern Science and Technology and Industrial Development of Jiangxi Traditional Medicine/ ; }, abstract = {BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG.

METHODS: In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG + AS-IV group, n = 5/group. In EAMG + AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4 weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n = 3/group. Fecal extractions from EAMG and EAMG + AS-IV groups as gathered above were used to administered daily to the respective groups for 4 weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA.

RESULTS: The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels.

CONCLUSION: This study speculated that AS-IV ameliorates EAMG by regulating CD4 + T cells and altering the structure and species of gut microbiota of EAMG.}, } @article {pmid37540090, year = {2023}, author = {McChalicher, CWJ and Lombardo, MJ and Khanna, S and McKenzie, GJ and Halvorsen, EM and Almomani, S and Schuster, B and Hasson, BR and McGovern, BH and Ege, DS and Auniņš, JG}, title = {Manufacturing Processes of a Purified Microbiome Therapeutic Reduce Risk of Transmission of Potential Bacterial Pathogens in Donor Stool.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiad298}, pmid = {37540090}, issn = {1537-6613}, abstract = {INTRODUCTION: Although fecal microbiota transplant has been used to prevent recurrent Clostridioides difficile infection (rCDI), documented pathogen transmission highlight inherent safety risks of minimally-processed stool. We describe manufacturing processes for fecal microbiota spores, live (VOWSTTM; VOS, formerly SER-109), a microbiota-based oral therapeutic of Firmicutes spores.

METHODS: Bacterial inactivation kill curves were obtained after ethanol exposure for four model organisms spiked into process intermediates.

RESULTS: Bacterial log reduction factors ranged from 6.5 log10 to 7.4 log10 and lysis of spiked organisms occurred rapidly within 30 seconds.

CONCLUSION: These experiments demonstrate substantial and rapid inactivation of representative organisms, supporting the potential benefit of VOS manufacturing processes to mitigate risk.}, } @article {pmid37537802, year = {2015}, author = {Lee, EW and Lucioni, A and Lee, UJ and Kobashi, KC}, title = {National Practice Patterns of Infection Prophylaxis for Sacral Neuromodulation Device: A Survey of High Volume Providers.}, journal = {Urology practice}, volume = {2}, number = {1}, pages = {38-43}, doi = {10.1016/j.urpr.2014.07.003}, pmid = {37537802}, issn = {2352-0787}, abstract = {INTRODUCTION: Sacral neuromodulation using the InterStim® device is a safe, effective treatment for urgency, frequency, urgency incontinence, nonobstructive urinary retention and fecal incontinence. However, there is no standard recommendation regarding infection prophylaxis. Therefore, we surveyed the infection prophylaxis patterns of high volume device providers to describe current practice patterns of perioperative infection prophylaxis.

METHODS: A web based survey was sent to 35 high volume providers, including urologists, gynecologists and colorectal surgeons.

RESULTS: Our response rate was 89% (31 of 35 participants). Of the providers 51% were urologists, 39% were gynecologists and 10% were colorectal surgeons. Of the respondents 74% had performed more than 200 procedures and 22% had done more than 500. The testing period was generally 1 to 2 weeks. Only 13% of the surveyed providers routinely screened for methicillin resistant Staphylococcus aureus. All providers administered antibiotics preoperatively, most commonly cefazolin or vancomycin, and 81% administered antibiotics postoperatively, most commonly cephalexin and trimethoprim-sulfamethoxazole. Most providers prescribed 5 to 7 days of treatment but 6 (19%) prescribed no postoperative antibiotics. In addition, 71% of respondents used adjunctive measures, frequently intraoperative wound irrigation and/or a preoperative chlorhexidine shower. After stages 1 and 2, 19% of providers prohibited showering for more than 3 days postoperatively while 61% permitted showering after 1 or 2 days and 19% recommended no bathing restriction.

CONCLUSIONS: We present the infection prevention practices of high volume InterStim sacral neuromodulation device implanters in the United States. Further study is warranted to guide evidence-based practice in InterStim infection prophylaxis.}, } @article {pmid37537245, year = {2023}, author = {Scott, AP and Henden, A and Kennedy, GA and Tey, SK}, title = {PET assessment of acute gastrointestinal graft versus host disease.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {37537245}, issn = {1476-5365}, abstract = {Acute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.}, } @article {pmid37537181, year = {2023}, author = {Wu, Q and Boonma, P and Badu, S and Yalcinkaya, N and So, SY and Garey, KW and Williams, K and Arnold, LE and Shulman, RJ and Kellermayer, R and Savidge, TC}, title = {Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {54}, pmid = {37537181}, issn = {2055-5008}, support = {P01-AI152999//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; U01-AI24290//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; R01-AI10091401//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; P30-DK56338//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; RO1 DK130517//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; }, abstract = {Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal donors are used. Furthermore, we demonstrated broad utility of high-resolution variant-calling by linking probiotic-strain engraftment with improved gastrointestinal symptoms in adults with irritable bowel syndrome and in children with autism spectrum disorder. Our findings emphasize the importance of strain-level identification when assessing the efficacy of probiotics and microbiota-based therapeutics.}, } @article {pmid37536860, year = {2023}, author = {Hyoju, S and Machutta, K and Krezalek, MA and Alverdy, JC}, title = {What Is the Role of the Gut in Wound Infections?.}, journal = {Advances in surgery}, volume = {57}, number = {1}, pages = {31-46}, doi = {10.1016/j.yasu.2023.05.002}, pmid = {37536860}, issn = {1878-0555}, abstract = {Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and silently travel to the wound site where they release their infectious payload. Genetic tracking of microbes at the strain level is now possible with genetic sequencing techniques and can clarify the origin of microbes that cause wound infections. An emerging field of dietary prehabilitation to modulate the microbiome before surgery is being described to improve infection-related outcomes from surgery.}, } @article {pmid37536616, year = {2023}, author = {Gupta, U and Dey, P}, title = {Rise of the guardians: Gut microbial maneuvers in bacterial infections.}, journal = {Life sciences}, volume = {}, number = {}, pages = {121993}, doi = {10.1016/j.lfs.2023.121993}, pmid = {37536616}, issn = {1879-0631}, abstract = {AIMS: Bacterial infections are one of the major causes of mortality globally. The gut microbiota, primarily comprised of the commensals, performs an important role in maintaining intestinal immunometabolic homeostasis. The current review aims to provide a comprehensive understanding of how modulation of the gut microbiota influences opportunistic bacterial infections.

MATERIALS AND METHODS: Primarily centered around mechanisms related to colonization resistance, nutrient, and metabolite-associated factors, mucosal immune response, and commensal-pathogen reciprocal interactions, we discuss how gut microbiota can promote or prevent bacterial infections.

KEY FINDINGS: Opportunistic infections can occur directly due to obligate pathogens or indirectly due to the overgrowth of opportunistic pathobionts. Gut microbiota-centered mechanisms of altered intestinal immunometabolic and metabolomic homeostasis play a significant role in infection promotion and prevention. Depletion in the population of commensals, increased abundance of pathobionts, and overall decrease in gut microbial diversity and richness caused due to prolonged antibiotic use are risk factors of opportunistic bacterial infections, including infections from multidrug-resistant spp. Gut commensals can limit opportunistic infections by mechanisms including the production of antimicrobials, short-chain fatty acids, bile acid metabolism, promoting mucin formation, and maintaining immunological balance at the mucosa. Gut microbiota-centered strategies, including the administration of probiotics and fecal microbiota transplantation, could help attenuate opportunistic bacterial infections.

SIGNIFICANCE: The current review discussed the gut microbial population and function-specific aspects contributing to bacterial infection susceptibility and prophylaxis. Collectively, this review provides a comprehensive understanding of the mechanisms related to the dual role of gut microbiota in bacterial infections.}, } @article {pmid37536115, year = {2023}, author = {Vagaggini, C and Brai, A and Bonente, D and Lombardi, J and Poggialini, F and Pasqualini, C and Barone, V and Nicoletti, C and Bertelli, E and Dreassi, E}, title = {Development and validation of derivatization-based LC-MS/MS method for quantification of short-chain fatty acids in human, rat, and mouse plasma.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {235}, number = {}, pages = {115599}, doi = {10.1016/j.jpba.2023.115599}, pmid = {37536115}, issn = {1873-264X}, abstract = {Short-chain fatty acids (SCFAs), the end products of gut microbial fermentation of dietary fibers and non-digestible polysaccharides, act as a link between the microbiome, immune system, and inflammatory processes. The importance of accurately quantifying SCFAs in plasma has recently emerged to understand their biological role. In this work, a sensitive and reproducible LC-MS/MS method is reported for SCFAs quantification in three different matrices such as human, rat and mouse plasma via derivatization, using as derivatizing agent O-benzylhydroxylamine (O-BHA), coupled with liquid-liquid extraction. First, the instrumental parameters of the mass spectrometer and then the chromatographic conditions were optimized using previously SCFAs derivatives synthetized and used as standards. After that, the best conditions for derivatization and extraction from plasma were studied and a series of determinations were performed on human, rat, and mouse plasma aliquots to validate the overall method (derivatization, extraction, and LC-MS/MS determination). The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%) and sensitivity (LOQ of 0.01 µM for acetic, butyric, propionic and isobutyric acid) in all plasma samples. The method thus developed and validated was applied to the quantification of major SCFAs in adult and aged mice, germ-free mice and in germ-free recipient mice subjected to fecal transplant from adult and aged donors. Results highlighted how plasma concentrations of SCFAs are correlated with age further highlighting the importance of developing a method that is reliable for the quantification of SCFAs to study their biological role.}, } @article {pmid37534844, year = {2023}, author = {Halue, G and Tharapanich, H and Phannajit, J and Kanjanabuch, T and Banjongjit, A and Lorvinitnun, P and Sritippayawan, S and Sopassathit, W and Poonvivatchaikarn, U and Buranaosot, S and Somboonsilp, W and Wongtrakul, P and Boonyakrai, C and Narenpitak, S and Tatiyanupanwong, S and Saikong, W and Uppamai, S and Panyatong, S and Chieochanthanakij, R and Lounseng, N and Wongpiang, A and Treamtrakanpon, W and Rattanasoonton, P and Lukrat, N and Songviriyavithaya, P and Parinyasiri, U and Rojsanga, P and Kanjanabuch, P and Puapatanakul, P and Pongpirul, K and Johnson, DW and Perl, J and Pecoits-Filho, R and Ophascharoensuk, V and Tungsanga, K and , }, title = {Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.}, journal = {Nephrology (Carlton, Vic.)}, volume = {28 Suppl 1}, number = {}, pages = {35-47}, doi = {10.1111/nep.14224}, pmid = {37534844}, issn = {1440-1797}, abstract = {BACKGROUND: Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes.

METHODS: We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis.

RESULTS: Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin.

CONCLUSION: Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.}, } @article {pmid37533870, year = {2023}, author = {Yao, K and Xie, Y and Wang, J and Lin, Y and Chen, X and Zhou, T}, title = {Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1202850}, pmid = {37533870}, issn = {1664-3224}, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.}, } @article {pmid37533828, year = {2023}, author = {Zhang, P and Chen, J and Ming, Y and Niu, Y}, title = {Probiotics treatment ameliorated mycophenolic acid-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1153188}, pmid = {37533828}, issn = {1664-302X}, abstract = {BACKGROUND: Mycophenolic acid (MPA)-induced colitis was still a severe side effect and challenge faced by solid transplant recipients. We aimed to explore the function and mechanism of probiotics in the treatment of MPA-induced colitis.

METHODS: In this study, 15 mice (C57BL/6) were randomly assigned into three groups: control (CNTL) group (n = 5), MPA group (n = 5) and the MPA + Probiotic group (n = 5). Bifid Triple Viable capsules, which were drugs for clinical use and consisted of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, were used in Probiotic group. Body weight change, stool scores, colon histopathology and morphology were used to evaluate the disease severity. The intestinal mucosal barrier function was assessed by measuring the expression level of secretory immunoglobulin A (sIgA), Zonula occludens-1 (ZO-1) and Occludin. Finally, 16S rDNA sequencing and bioinformatics analysis were performed on mice feces to compare the different intestinal microbial composition and diversity among three groups.

RESULTS: Compared with the CNTL group, the mice in MPA group showed a significantly decreased body weight, increased stool scores, shortened colon length and severe colon inflammation. However, probiotics treated MPA mice reversed the disease severity, indicating that probiotics ameliorated MPA-induced colitis in mice. Mechanistically, probiotics improved the intestinal barrier function by up-regulating the expression of sIgA, ZO-1 and Occludin. Moreover, MPA-induced colitis led to intestinal microbiota dysbiosis, including the change of Firmicutes/Bacteroidetes ratio, α- and β-diversity. But probiotic treated group showed mild change in these microbial features. Additionally, we found that Clostridiales was the most significantly different microbiota flora in MPA group.

CONCLUSION: Probiotics treatment ameliorated MPA-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis. Clostridiales might be the dominant functional intestinal microflora and serve as the potential therapy target in MPA-induced colitis.}, } @article {pmid37533076, year = {2023}, author = {Yang, X and Li, D and Zhang, M and Feng, Y and Jin, X and Liu, D and Guo, Y and Hu, Y}, title = {Ginkgo biloba extract alleviates fatty liver hemorrhagic syndrome in laying hens via reshaping gut microbiota.}, journal = {Journal of animal science and biotechnology}, volume = {14}, number = {1}, pages = {97}, pmid = {37533076}, issn = {1674-9782}, support = {2022YFA1304201//National Key Research and Development Program of China/ ; 6222032//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.

RESULTS: The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis (FAS, LXRα, GPAT1, PPARγ and ChREBP1) and inflammatory cytokines (TNF-α, IL-6, TLR4 and NF-κB) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT).

CONCLUSIONS: We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.}, } @article {pmid37527781, year = {2023}, author = {Ranjbarian, T and Schnabl, B}, title = {Gut-microbiome centered therapies for alcohol-associated liver disease.}, journal = {Seminars in liver disease}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2145-7331}, pmid = {37527781}, issn = {1098-8971}, abstract = {Globally, liver disease caused by alcohol is becoming more prevalent each year. Misuse of alcohol causes a spectrum of liver diseases, such as liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The cornerstone of treatment is abstinence from alcohol. In spite of this, available treatment for alcohol-associated liver disease (ALD) shows limited effectiveness at the present time. There are numerous ways in which alcohol disrupts the gut-liver axis, including dysbiosis of the gut microbiome, disruption of mucus and epithelial cell barriers, impaired production of antimicrobial molecules, and dysfunction of the immune system, causing translocation of viable microbes and microbial products to the liver and systemic circulation. Microbial exposure not only results in inflammation and progression of liver disease, but also infections in late stage ALD. This led scientists to focus their therapeutic strategies and targets for ALD on the gut microbiome. Throughout this review, we address the role of gut microbiome centered therapeutic approaches for ALD focusing predominantly on randomized controlled trials. We will summarize the latest clinical trials using probiotics, antibiotics, fecal microbial transplants in modulating the gut liver axis and for improvement of ALD.}, } @article {pmid37527604, year = {2023}, author = {Yi, X and Cai, R and Shaoyong, W and Wang, G and Yan, W and He, Z and Li, R and Chao, M and Zhao, T and Deng, L and Yang, G and Pang, W}, title = {Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome.}, journal = {Redox biology}, volume = {65}, number = {}, pages = {102829}, doi = {10.1016/j.redox.2023.102829}, pmid = {37527604}, issn = {2213-2317}, abstract = {Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.}, } @article {pmid37527003, year = {2023}, author = {Puerta-Alcalde, P and Garcia-Vidal, C and Soriano, A}, title = {Prevention and treatment of C. difficile in cancer patients.}, journal = {Current opinion in infectious diseases}, volume = {}, number = {}, pages = {}, pmid = {37527003}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients.

RECENT FINDINGS: Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates.

SUMMARY: Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.}, } @article {pmid37524154, year = {2023}, author = {Yan, J and Duan, W and Gao, Q and Mao, T and Wang, M and Duan, J and Li, J}, title = {ENPP2 inhibitor improves proliferation in AOM/DSS-induced colorectal cancer mice via remodeling the gut barrier function and gut microbiota composition.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106877}, doi = {10.1016/j.phrs.2023.106877}, pmid = {37524154}, issn = {1096-1186}, abstract = {In our previous multicenter study, we delineated the inherent metabolic features of colorectal cancer (CRC). Therein, we identified a member of the ectonucleotide pyrophosphatase/ phosphodiesterase family (ENPP2) as a significant differential metabolite of CRC. In this study, the role of ENPP2 in CRC has been demonstrated using established in vitro and in vivo models including ENPP2 gene knockdown, and use of the ENPP2 inhibitor, GLPG1690. We found that CRC proliferation was decreased after either ENPP2 gene knockdown or use of ENPP2 inhibitors. We further evaluated the role of GLPG1690 in AOM/DSS-induced CRC mice via intestinal barrier function, macrophage polarization, inflammatory response and microbial homeostasis. Results of immunofluorescence staining and Western blotting showed that GLPG1690 can restore gut-barrier function by increasing the expression of tight junction proteins, claudin-1, occludin and ZO-1. M2 tumor-associated macrophage polarization and colonic inflammation were attenuated after treatment with GLPG1690 using the Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) model. Moreover, 16S rDNA pyrosequencing and metagenomic analysis showed that GLPG1690 could alleviate gut dysbiosis in mice. Furthermore, administration of GLPG1690 with antibiotics as well as fecal microbiota transplantation assays demonstrated a close link between the efficacy of GLPG1690 and the gut microbiota composition. Finally, results of metabolomic analysis implicated mainly the gut microbiota-derived metabolites of aromatic amino acids in CRC progression. These findings may provide novel insights into the development of small-molecule ENPP2 inhibitors for the treatment of CRC.}, } @article {pmid37523293, year = {2023}, author = {Maigoro, AY and Muhammad, M and Bello, B and Useh, U and Lee, S}, title = {Exploration of Gut Microbiome Research in Africa: A Scoping Review.}, journal = {Journal of medicinal food}, volume = {}, number = {}, pages = {}, doi = {10.1089/jmf.2023.K.0005}, pmid = {37523293}, issn = {1557-7600}, abstract = {The crucial role of the gut microbiome in various diseases has led to increased interest in interventions and therapeutics targeting the human microbiome. Accordingly, the current scoping review analyzed the diseases and interventions involved in gut microbiome research in Africa. The electronic databases of PubMed, Google Scholar, and Scopus were searched from inception to October 2021. This study identified 48 studies involving 7073 study participants. Of the 48 studies, 20 (42%) used interventions to modulate gut microbiota, whereas the remaining 28 (58%) did not. Out of the total African countries, only 13% were involved in intervention-based gut microbiome research, whereas a larger proportion of 67% were not involved in any gut microbiome research. The interventions used in gut microbiome research in Africa include supplements, natural products, educational approaches, associated pathogens, albendazole, fresh daily yogurt, iron-containing lipid-based nutrient supplements, fecal microbiota transplant, and prophylactic cotrimoxazole. This scoping review highlights the current state of gut microbiome research in Africa. The findings of this review can inform the design of future studies and interventions aimed at improving gut health in African populations.}, } @article {pmid37521153, year = {2023}, author = {Alfuzaie, R}, title = {The Link Between Gastrointestinal Microbiome and Ocular Disorders.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {17}, number = {}, pages = {2133-2140}, pmid = {37521153}, issn = {1177-5467}, abstract = {The gut-eye axis has been hypothesized to be a factor in many eye pathologies. This review examines papers from PubMed about this topic. Bacterial commensals could either be protective by regulating the immune system or prove to be damaging to the gut mucosal wall and incite an inflammatory process. The balance between the two appears to be crucial in maintaining eye health. Imbalances have been implicated in ophthalmologic conditions. The use of probiotics, dietary modifications, antibiotics, and faecal microbiota transplant in mice with pathologies such as those encountered in our practice appears to reverse disease course or at least prevent its progression. Clinical trials are currently underway to investigate their clinical significance in diseased patients.}, } @article {pmid37518975, year = {2023}, author = {Van Jacobs, A and Williams, MD and Ralph, OG and Becerra, AZ and Chan, EY and Olaitan, O}, title = {Pancreatic Exocrine Secretion and Weight Gain After Pancreas Transplantation.}, journal = {Progress in transplantation (Aliso Viejo, Calif.)}, volume = {}, number = {}, pages = {15269248231189877}, doi = {10.1177/15269248231189877}, pmid = {37518975}, issn = {2164-6708}, abstract = {INTRODUCTION: Weight gain after pancreas transplant is a poorly understood phenomenon thought to be related to increased posttransplant insulin production, immunosuppressive medications, and appetite changes. No study has investigated the effect of increased exocrine secretion posttransplant.

AIMS AND HYPOTHESIS: We hypothesized that exocrine function, measured by fecal elastase-1 (FE-1), was normal posttransplant and not correlated with weight gain. Our primary aim was to investigate changes in FE-1 levels with pancreas transplantation and to correlate this with weight gain. Establishing weight trends and identifying additional correlating factors were secondary aims.

DESIGN: Forty-two patients that underwent simultaneous pancreas and kidney or pancreas after kidney transplant at a single center between 2013 and 2021 were included. Fecal elastase was measured prospectively in each patient at a single time point, with >500 µg/g categorized as high. Weight and C-peptide values were obtained. All the patients were on steroid-free immunosuppression.

RESULTS: Nineteen patients (45%) had fecal elastase levels >500 µg/g, with a maximum of 3910 µg/g; 43% had levels greater than twice the upper limit of normal. The biggest increase in weight occurred between years 1 and 2, which continued to a median weight gain of 14% at 3 years. There was no correlation between weight gain and FE-1, pretransplant C-peptide levels, or duration of diabetes.

CONCLUSION: This study demonstrated supranormal fecal elastase levels and weight gain posttransplant; however, there was no correlation. Future study with serial FE-1 before and after transplant is needed to better assess its correlation with weight gain.}, } @article {pmid37517290, year = {2023}, author = {Li, L and Yang, J and Liu, T and Shi, Y}, title = {Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {165}, number = {}, pages = {115243}, doi = {10.1016/j.biopha.2023.115243}, pmid = {37517290}, issn = {1950-6007}, abstract = {Brain injury, a common complication in preterm infants, includes the destruction of the key structural and functional connections of the brain and causes neurodevelopmental disorders; it has high morbidity and mortality rates. The exact mechanism underlying brain injury in preterm infants is unclear. Intestinal flora plays a vital role in brain development and the maturation of the immune system in infants; however, detailed understanding of the gut microbiota-metabolite-brain axis in preterm infants is lacking. In this review, we summarise the key mechanisms by which the intestinal microbiota contribute to neurodevelopment and brain injury in preterm infants, with special emphasis on the influence of microorganisms and their metabolites on the regulation of neurocognitive development and neurodevelopmental risks related to preterm birth, infection and neonatal necrotising enterocolitis (NEC). This review provides support for the development and application of novel therapeutic strategies, including probiotics, prebiotics, synbiotics, and faecal bacteria transplantation targeting at brain injury in preterm infants.}, } @article {pmid37516837, year = {2023}, author = {Salonen, T and Jokinen, E and Satokari, R and Lahtinen, P}, title = {Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {513}, pmid = {37516837}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; Adult ; *Fatigue Syndrome, Chronic/therapy ; Fecal Microbiota Transplantation ; Pilot Projects ; Quality of Life ; Double-Blind Method ; }, abstract = {BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.

METHODS: Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2 years and mean duration of CFS 6.3 years) were randomly assigned to receive either FMT from a universal donor (n = 5) or autologous FMT (n = 6) via colonoscopy. Patients' HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients' HRQOL was evaluated at baseline, and 1 and 6 months after the FMT.

RESULTS: The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p = 0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p = 0.80), 53.5 and 62.0 at 1 month and 58.6 and 56.2 at 6 months. Compared to the baseline scores, differences at 1 and 6 months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.

CONCLUSION: FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results. Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.

CLINICALTRIALS: gov , date of registration 08/08/2019.}, } @article {pmid37511862, year = {2023}, author = {Hu, D and Zhao, J and Zhang, H and Wang, G and Gu, Z}, title = {Fecal Microbiota Transplantation for Weight and Glycemic Control of Obesity as Well as the Associated Metabolic Diseases: Meta-Analysis and Comprehensive Assessment.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37511862}, issn = {2075-1729}, abstract = {Objectives: An analysis of the weight and blood glucose management associated with fecal microbiota transplantation (FMT) as well as metabolic diseases associated with FMT was conducted by the authors in order to provide clinical recommendations regarding the treatment of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods: We searched PubMed, Embase, and the Cochrane Library for papers that were published between the creation of the database and October 2022. We reviewed research that investigated how FMT affected weight and glycemic management in cases of obesity and metabolic conditions that are related to obesity. Studies that were published more than once, lacked the entire text, included insufficient information, or were impossible to extract data from were excluded. Additionally, case reports, reviews, and systematic reviews were excluded from the analysis. In order to analyze the data, STATA 15.1 was used. Outcomes: When we combined all of our findings, we discovered that pooled outcomes showed that weight levels (WMD equals -4.77, 95%CI: -7.40~-2.14), BMI levels (WMD equals -1.59, 95%CI: -2.21~-0.97), HOMA-IR (WMD equals -0.79, 95%CI: -1.57~-0.00), and HbA1c (WMD equals -0.65, 95%CI: -0.75~-0.55) after FMT treatment were significantly lower than before treatment. However, FMT treatment may have no effect on glucose and insulin levels in obese patients at fasting and related metabolic diseases. Additionally, subgroup analysis outcomes found that FMT significantly reduced fasting blood glucose in people with diabetes. Conclusions: As a weight loss and glycemic control therapy, FMT helps to prevent and treat metabolic problems linked to obesity, and is a viable alternative to bariatric surgery for patients who do not wish to undergo the procedure.}, } @article {pmid37511151, year = {2023}, author = {Ahn, JS and Choi, YJ and Kim, HB and Chung, HJ and Hong, ST}, title = {Identification of the Intestinal Microbes Associated with Locomotion.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511151}, issn = {1422-0067}, support = {C380300//Korea Basic Science Institute/ ; C320000//Korea Basic Science Institute/ ; C330340//Korea Basic Science Institute/ ; HV22C0171//Korea Health Industry Development Institute/Republic of Korea ; RS-2023-00224099//National Research Foundation of Korea/ ; }, abstract = {Given the impact of the gut microbiome on human physiology and aging, it is possible that the gut microbiome may affect locomotion in the same way as the host's own genes. There is not yet any direct evidence linking the gut microbiome to locomotion, though there are some potential connections, such as regular physical activity and the immune system. In this study, we demonstrate that the gut microbiome can contribute differently to locomotion. We remodeled the original gut microbiome of mice through fecal microbiota transplantation (FMT) using human feces and compared the changes in locomotion of the same mice before and three months after FMT. We found that FMT affected locomotion in three different ways: positive, none (the same), and negative. Analysis of the phylogenesis, α-diversities, and β-diversities of the gut microbiome in the three groups showed that a more diverse group of intestinal microbes was established after FMT in each of the three groups, indicating that the human gut microbiome is more diverse than that of mice. The FMT-remodeled gut microbiome in each group was also different from each other. Fold change and linear correlation analyses identified Lacrimispora indolis, Pseudoflavonifractor phocaeensis, and Alistipes senegalensis in the gut microbiome as positive contributors to locomotion, while Sphingobacterium cibi, Prevotellamassilia timonensis, Parasutterella excrementihominis, Faecalibaculum rodentium, and Muribaculum intestinale were found to have negative effects. This study not only confirms the presence of gut microbiomes that contribute differently to locomotion, but also explains the mixed results in research on the association between the gut microbiome and locomotion.}, } @article {pmid37511148, year = {2023}, author = {Yan, X and Bai, L and Qi, P and Lv, J and Song, X and Zhang, L}, title = {Potential Effects of Regulating Intestinal Flora on Immunotherapy for Liver Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, doi = {10.3390/ijms241411387}, pmid = {37511148}, issn = {1422-0067}, abstract = {The intestinal flora plays an important role in the occurrence and development of liver cancer, affecting the efficacy and side effects of conventional antitumor therapy. Recently, immunotherapy for liver cancer has been a palliative treatment for patients with advanced liver cancer lacking surgical indications. Representative drugs include immune checkpoint inhibitors, regulators, tumor vaccines, and cellular immunotherapies. The effects of immunotherapy on liver cancer vary because of the heterogeneity of the tumors. Intestinal flora can affect the efficacy and side effects of immunotherapy for liver cancer by regulating host immunity. Therefore, applying probiotics, prebiotics, antibiotics, and fecal transplantation to interfere with the intestinal flora is expected to become an important means of assisting immunotherapy for liver cancer. This article reviews publications that discuss the relationship between intestinal flora and immunotherapy for liver cancer and further clarifies the potential relationship between intestinal flora and immunotherapy for liver cancer.}, } @article {pmid37510327, year = {2023}, author = {Liu, P and Zhang, Y and Zhang, Z and Huang, X and Su, X and Yang, S and Xie, Y}, title = {Antibiotic-Induced Dysbiosis of the Gut Microbiota Impairs Gene Expression in Gut-Liver Axis of Mice.}, journal = {Genes}, volume = {14}, number = {7}, pages = {}, doi = {10.3390/genes14071423}, pmid = {37510327}, issn = {2073-4425}, support = {Project No. CYS21324，Project No. cstc2021jcyj- msxmX0834//Chongqing Postgraduate Research Innovation Program ，Chongqing Natural Science Foundation/ ; }, abstract = {Antibiotics can be a double-edged sword. The application of broad-spectrum antibiotics leads to the suppression of microorganisms in the human body without selective targeting, including numerous non-pathogenic microorganisms within the gut. As a result, dysbiosis of the gut microbiota can occur. The gut microbiota is a vast and intricate ecosystem that has been connected with various illnesses. Significantly, the gut and liver function in a closely coupled anatomical and physiological relationship referred to as the "gut-liver axis". Consequently, metabolites stemming from the gut microbiota migrate via the portal vein to the liver, thereby influencing gene expression and proper physiological activity within the liver. This study aimed to investigate the dysbiosis of gut microbiota ecology and the disruption of gene expression resulting from oral antibiotics and their subsequent recovery. In the experiment, mice were tube-fed neomycin (0.5 mg/mL) and ampicillin (1 mg/mL) for 21 days (ABX group) to conduct 16s rRNA sequencing. By simultaneously analyzing public datasets PRJDB6615, which utilized the same antibiotics, it was found that nearly 50% of the total microbiota abundance was attributed to the f__Lactobacillaceae family. Additionally, datasets GSE154465 and GSE159761, using the same antibiotics, were used to screen for differentially expressed genes pre-and post-antibiotic treatment. Quantitative real-time PCR was employed to evaluate gene expression levels before and after antibiotic treatment. It was discovered that oral antibiotics significantly disrupted gene expression in the gut and liver, likely due to the dysregulation of the gut microbiota ecology. Fecal microbiota transplantation (FMT) was found to be an effective method for restoring gut microbiota dysbiosis. To further enhance the restoration of gut microbiota and gene expression, an antioxidant, vitamin C, was added to the FMT process to counteract the oxidative effect of antibiotics on microorganisms. The results showed that FMTs with vitamin C were more effective in restoring gut microbiota and gene expression to the level of the fecal transplant donor.}, } @article {pmid37509487, year = {2023}, author = {López-Villodres, JA and Escamilla, A and Mercado-Sáenz, S and Alba-Tercedor, C and Rodriguez-Perez, LM and Arranz-Salas, I and Sanchez-Varo, R and Bermúdez, D}, title = {Microbiome Alterations and Alzheimer's Disease: Modeling Strategies with Transgenic Mice.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/biomedicines11071846}, pmid = {37509487}, issn = {2227-9059}, support = {C1 from Plan Propio//University of Malaga/ ; }, abstract = {In the last decade, the role of the microbiota-gut-brain axis has been gaining momentum in the context of many neurodegenerative and metabolic disorders, including Alzheimer's disease (AD) and diabetes, respectively. Notably, a balanced gut microbiota contributes to the epithelial intestinal barrier maintenance, modulates the host immune system, and releases neurotransmitters and/or neuroprotective short-chain fatty acids. However, dysbiosis may provoke immune dysregulation, impacting neuroinflammation through peripheral-central immune communication. Moreover, lipopolysaccharide or detrimental microbial end-products can cross the blood-brain barrier and induce or at least potentiate the neuropathological progression of AD. Thus, after repeated failure to find a cure for this dementia, a necessary paradigmatic shift towards considering AD as a systemic disorder has occurred. Here, we present an overview of the use of germ-free and/or transgenic animal models as valid tools to unravel the connection between dysbiosis, metabolic diseases, and AD, and to investigate novel therapeutical targets. Given the high impact of dietary habits, not only on the microbiota but also on other well-established AD risk factors such as diabetes or obesity, consistent changes of lifestyle along with microbiome-based therapies should be considered as complementary approaches.}, } @article {pmid37507843, year = {2023}, author = {Zhong, HJ and Chen, WR and Lu, XJ and Hu, DX and Lin, DJ and Liu, T and Wu, L and Wu, LH and He, XX}, title = {Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.}, journal = {European journal of clinical investigation}, volume = {}, number = {}, pages = {e14072}, doi = {10.1111/eci.14072}, pmid = {37507843}, issn = {1365-2362}, support = {2021KCXTD025//the Education Department of Guangdong Province/ ; 2022B1111070006//the Guangdong Provincial Department of Science and Technology/ ; }, abstract = {BACKGROUND: Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD.

METHODS: We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment.

RESULTS: Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p < .05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD.

CONCLUSIONS: Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.}, } @article {pmid37505972, year = {2023}, author = {Gao, J and Nie, R and Chang, H and Yang, W and Ren, Q}, title = {A meta-analysis of microbiome therapies for hepatic encephalopathy.}, journal = {European journal of gastroenterology & hepatology}, volume = {35}, number = {9}, pages = {927-937}, doi = {10.1097/MEG.0000000000002596}, pmid = {37505972}, issn = {1473-5687}, abstract = {Microbiome therapies may be reported to be effective in hepatic encephalopathy (HE). We thus did a meta-analysis of randomized controlled trials to assess the effect of microbiome therapies for HE. We systematically searched PubMed, Web of Science, EMBASE, and Cochrane Library for randomized controlled trials that compared the different treatments for HE including probiotics, symbiotics, and fecal microbiota transplant (FMT). Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Twenty-one studies met our inclusion criteria (N = 1746 participants). Probiotics, synbiotics and FMT significantly reversed minimal HE (MHE) (OR: 0.41, 95% CI: 0.19-0.90, P = 0.03), reduced overt HE (OHE) development (OR, 0.41; 95% CI: 0.28-0.61 P < 0.00001)and the frequency of serious adverse events(SAEs) (OR:0.14, 95% CI: 0.04-0.47, P = 0.001), meanwhile decreased ammonia levels (WMD: -9.26, 95% CI: -16.92 to -1.61; P = 0.02), NCT level (MD = -4.41, 95% CI: -0.87 to -0.22, P = 0.04) and hospitalization rates (OR, 0.38; 95% CI: 0.19-0.79, P = 0.009) compared with placebo/no treatment. Finally, we conclude that microbiome therapies were more effective in improving MHE and preventing progression to OHE, reducing the frequency of SAEs, and decreasing ammonia levels, NCT level, and hospitalization rates when compared to placebo/no treatment.}, } @article {pmid37505920, year = {2023}, author = {Tan, J and Hu, R and Gong, J and Fang, C and Li, Y and Liu, M and He, Z and Hou, DX and Zhang, H and He, J and Wu, S}, title = {Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2238959}, doi = {10.1080/19490976.2023.2238959}, pmid = {37505920}, issn = {1949-0984}, abstract = {Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.}, } @article {pmid37504971, 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 alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo01929b}, pmid = {37504971}, issn = {2042-650X}, abstract = {Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from Rhodiola rosea L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg[-1] of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of Turicibacter, Alistipes, Romboutsia and the increased relative abundance of Lactobacillus at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.}, } @article {pmid37503350, year = {2023}, author = {Yang, S and Liu, G and Savelkoul, HFJ and Jansen, CA and Li, B}, title = {Mini-review: microbiota have potential to prevent PEDV infection by improved intestinal barrier.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1230937}, pmid = {37503350}, issn = {1664-3224}, abstract = {Porcine epidemic diarrhea virus (PEDV) infection poses a significant threat to the global pig industry. Current prevention and control strategies are inadequate in protecting pigs from new PEDV variants. This review aims to examine the relationship between PEDV and intestinal microbes, and investigate whether modulating intestinal microbes could affect PEDV infection. The mechanisms by which various intestinal microbes affect viral infection were initially introduced. Intestinal microbes can influence enteric viral infection through direct contact, such as binding, or by affecting interferons (IFNs) production and the intestinal barrier. Influencing the intestinal barrier by microbes can impact PEDV infection in young piglets. To narrow down the range of microbes that may influence PEDV infection, this review summarized microbes that change after infection. Short chain fatty acids (SCFAs), bacterial cell components, and toxins from microbes were identified as important mediators affecting PEDV infection. SCFAs primarily strengthen the intestinal barrier and inhibit intestinal inflammation, while bacterial cell components and toxins are more likely to damage the intestinal barrier. Therefore, this review hypothesizes that fecal transplantation, which allows the host to colonize more SCFAs-producing microbes, may prevent PEDV infection. However, these hypotheses require further proof, and the transplantation of intestinal microbes in pigs requires more exploration.}, } @article {pmid37503065, year = {2023}, author = {Akbarali, H and Muchhala, K and Kang, M and Koseli, E and Poklis, J and Xu, Q and Dewey, W and Fettweis, J and Jimenez, N}, title = {The Role of Morphine-Induced Impairment of Intestinal Epithelial Antibacterial Activity in Dysbiosis and its Impact on the Microbiota-Gut-Brain Axis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-3084467/v1}, pmid = {37503065}, abstract = {Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the gut epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that intestinal antimicrobial activity is reduced, and epithelial permeability is increased in a morphine-dependent mouse model. Antimicrobial activity and permeability are restored by fecal transplant (FMT) from morphine-naïve mice or by oral gavage of sodium butyrate. Butyrate levels are reduced in the fecal samples of morphine-treated mice concomitant with a reduction in the phylum, Firmicutes . The alpha diversity of the microbiome is also restored by oral butyrate in morphine-dependent mice. FMT or sodium butyrate prevents downregulation of the antimicrobial peptide, Regenerating islet-derived 3 gamma (Reg3γ), and the development of antinociceptive tolerance in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which morphine disrupts the microbiota-gut-brain axis.}, } @article {pmid37498052, year = {2023}, author = {Huang, Z and Li, Y and Park, H and Ho, M and Bhardwaj, K and Sugimura, N and Lee, HW and Meng, H and Ebert, MP and Chao, K and Burgermeister, E and Bhatt, AP and Shetty, SA and Li, K and Wen, W and Zuo, T}, title = {Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2237645}, doi = {10.1080/19490976.2023.2237645}, pmid = {37498052}, issn = {1949-0984}, abstract = {The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.}, } @article {pmid37495339, year = {2023}, author = {Barber, TM and Hanson, P and Weickert, MO}, title = {Metabolic-Associated Fatty Liver Disease and the Gut Microbiota.}, journal = {Endocrinology and metabolism clinics of North America}, volume = {52}, number = {3}, pages = {485-496}, doi = {10.1016/j.ecl.2023.01.004}, pmid = {37495339}, issn = {1558-4410}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/etiology/therapy ; Liver/metabolism/pathology ; *Probiotics/therapeutic use ; Bile Acids and Salts/metabolism ; }, abstract = {As an important sequela of the burgeoning global obesity problem, metabolic-associated fatty liver disease (MAFLD) has gained increasing prominence recently. The gut-liver axis (GLA) provides a direct conduit to the liver for the gut microbiota and their metabolic by-products (including secondary bile acids, ethanol, and trimethylamine). These GLA-related factors, including the host inflammatory response and integrity of the gut mucosal wall, likely contribute to the pathogenesis of MAFLD. Accordingly, these GLA-related factors are targets for possible preventive and treatment strategies for MAFLD, and include probiotics, prebiotics, bile acids, short-chain fatty acids, fecal microbiota transplantation, carbon nanoparticles, and bacteriophages.}, } @article {pmid37494556, year = {2023}, author = {Gedgaudas, R and Bajaj, JS and Skieceviciene, J and Valantiene, I and Kiudeliene, E and Bang, C and Franke, A and Schreiber, S and Kupcinskas, J}, title = {Sterile Fecal Filtrate From A Healthy Donor Improves Microbial Diversity In Patients With Hepatic Encephalopathy.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {}, number = {}, pages = {}, doi = {10.15403/jgld-4906}, pmid = {37494556}, issn = {1842-1121}, abstract = {BACKGROUND AND AIMS: Hepatic encephalopathy (HE) remains one of the most debilitating complications of liver cirrhosis. Changes in gut microbiome composition have been linked to liver diseases and its complications including HE. Recent randomized controlled trials showed fecal microbiota transplantation to be safe and effective in HE treatment, however transferring unidentified live bacteria could cause various complications, including infections, especially in immunocompromised patients. This study aimed to evaluate the safety and efficacy of sterile fecal filtrate transfer (SFFT) for the modulation of the intestinal microbiome of patients with cirrhosis and HE.

METHODS: A custom-made air pressure filtration device was used for the sterile fecal filtrate preparation. Seven patients received SFFT from the same healthy donor. Patients were monitored at least 30 days after the procedure. Cognition tests, blood and stool sampling were performed to assess the safety and efficacy of SFFT on HE, liver function, and stool microbiome composition on follow-up days 7 and 30.

RESULTS: SFFT was well tolerated and resulted in fluctuations in the microbial composition of study participants: α-diversity increased in 4/7 of the patients, without robust engraftment of donors' microbial composition as assessed by β-diversity analysis. No significant effect on cognition tests or liver function was noted after the procedure. One death occurred three months after the procedure, however, it was not related to the SFFT.

CONCLUSIONS: Despite the effect on the gut microbiome, we did not observe robust improvement in patients' liver function or HE cognition tests after the procedure.}, } @article {pmid37493938, year = {2023}, author = {Berry, P and Khanna, S}, title = {Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {}, number = {}, pages = {}, pmid = {37493938}, issn = {1179-190X}, abstract = {Clostridioides difficile is one of the most important causes of healthcare-associated diarrhea. The high incidence and recurrence rates of C. difficile infection, as well as its associated morbidity and mortality, are great concerns. The most common complication of C. difficile infection is recurrence, with rates of 20-30% after a primary infection and 60% after three or more episodes. Medical management of recurrent C. difficile infection involves a choice of therapy that is different from the antibiotic used in the primary episode. Patients with recurrent C. difficile infection also benefit from fecal microbiota transplantation or standardized microbiome restoration therapies (approved or experimental) to restore eubiosis. In contrast to antibiotics, microbiome restoration therapies restore a normal gut flora and eliminate C. difficile colonization and infection. Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo. Fecal microbiota transplantation has traditionally been considered safe, with the most common adverse reactions being abdominal discomfort, and diarrhea, and rare serious adverse events. Significant heterogeneity and a lack of standardization regarding the process of preparation, and administration of fecal microbiota transplantation remain a major pitfall. Standardized microbiome-based therapies provide a promising alternative. In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%. Both these agents are now US Food and Drug Administration approved for recurrent C. difficile infection. Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection.}, } @article {pmid37491512, year = {2023}, author = {Pernigoni, N and Guo, C and Gallagher, L and Yuan, W and Colucci, M and Troiani, M and Liu, L and Maraccani, L and Guccini, I and Migliorini, D and de Bono, J and Alimonti, A}, title = {The potential role of the microbiota in prostate cancer pathogenesis and treatment.}, journal = {Nature reviews. Urology}, volume = {}, number = {}, pages = {}, pmid = {37491512}, issn = {1759-4820}, abstract = {The human body hosts a complex and dynamic population of trillions of microorganisms - the microbiota - which influences the body in homeostasis and disease, including cancer. Several epidemiological studies have associated specific urinary and gut microbial species with increased risk of prostate cancer; however, causal mechanistic data remain elusive. Studies have associated bacterial generation of genotoxins with the occurrence of TMPRSS2-ERG gene fusions, a common, early oncogenic event during prostate carcinogenesis. A subsequent study demonstrated the role of the gut microbiota in prostate cancer endocrine resistance, which occurs, at least partially, through the generation of androgenic steroids fuelling oncogenic signalling via the androgen receptor. These studies present mechanistic evidence of how the host microbiota might be implicated in prostate carcinogenesis and tumour progression. Importantly, these findings also reveal potential avenues for the detection and treatment of prostate cancer through the profiling and modulation of the host microbiota. The latter could involve approaches such as the use of faecal microbiota transplantation, prebiotics, probiotics, postbiotics or antibiotics, which can be used independently or combined with existing treatments to reverse therapeutic resistance and improve clinical outcomes in patients with prostate cancer.}, } @article {pmid37491256, year = {2023}, author = {He, S and Li, J and Yao, Z and Gao, Z and Jiang, Y and Chen, X and Peng, L}, title = {Insulin alleviates murine colitis through microbiome alterations and bile acid metabolism.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {498}, pmid = {37491256}, issn = {1479-5876}, support = {81900506//National Natural Science Foundation of China/ ; 2019M662871//China Postdoctoral Science Foundation/ ; 2020T130133//China Postdoctoral Science Foundation/ ; 2018A030313970//National Science Foundation of Guangdong/ ; 2021A1515012162//National Science Foundation of Guangdong/ ; 202102020798//Basic and Applied Research Program of Guangzhou/ ; 202102010319//Basic Research Project of Peak Hospital/ ; }, abstract = {BACKGROUND: Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota.

METHODS: We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin.

RESULTS: We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages.

CONCLUSION: Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD.}, } @article {pmid37486121, year = {2023}, author = {Zhang, K and Yang, J and Chen, L and He, J and Qu, D and Zhang, Z and Liu, Y and Li, X and Liu, J and Li, J and Xie, X and Wang, Q}, title = {Gut Microbiota Participates in Polystyrene Microplastics-Induced Hepatic Injuries by Modulating the Gut-Liver Axis.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.3c04449}, pmid = {37486121}, issn = {1936-086X}, abstract = {Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.}, } @article {pmid37484415, year = {2023}, author = {Churchward, MA and Michaud, ER and Mullish, BH and Miguens Blanco, J and Garcia Perez, I and Marchesi, JR and Xu, H and Kao, D and Todd, KG}, title = {Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16908}, pmid = {37484415}, issn = {2405-8440}, abstract = {The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.}, } @article {pmid37483406, year = {2023}, author = {Shi, H and Chen, M and Zheng, C and Yinglin, B and Zhu, B}, title = {Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats.}, journal = {Journal of pain research}, volume = {16}, number = {}, pages = {2419-2432}, pmid = {37483406}, issn = {1178-7090}, abstract = {PURPOSE: Paclitaxel-induced peripheral neuropathy (PIPN) constitutes a refractory and progressive adverse consequence of paclitaxel treatment, causing pain and sensory anomalies in cancer survivors. Although the gut-brain axis is involved in multiple disorders including cancer, its impact on peripheral pain conditions remains elusive. Thus, we assessed the importance of gut microbiota and related mechanisms in PIPN.

METHODS: By implementing fecal microbiota transplantation (FMT) in a rat PIPN model (ie, rats treated with paclitaxel; hereafter as PIPN rats), we explored the effect of gut microbiota on PIPN rats using multiple methods, including different behavioral tests, 16S ribosomal DNA (rDNA) sequencing, and biochemical techniques.

RESULTS: Sequencing of 16S rDNA revealed that the abundance of genera Bacteroides and UCG-005 increased, while that of genera Turicibacter, Clostridium sensu stricto 1 and Corynebacterium decreased in the PIPN rats. However, when treated with FMT using fecal from normal rats, the mechanical allodynia and thermal hyperalgesia in PIPN rats were significantly alleviated. In addition, FMT treatment reduced the expression of toll-like receptor 4 (TLR4), phospho-p38 mitogen-activated protein kinase (p-p38MAPK), and the astrocytic marker glial fibrillary acidic protein in the colon and spinal dorsal horn. TAK242 (a TLR4 inhibitor) significantly alleviated the behavioral hypersensitivity of PIPN rats and inhibited the TLR4/p38MAPK pathway in astrocytes in these rats.

CONCLUSION: The gut microbiota played a critical role in PIPN. Future therapies treating PIPN should consider microbe-based treatment as an option.}, } @article {pmid37482926, year = {2023}, author = {Baunwall, SMD and Hansen, MM and Andreasen, SE and Eriksen, MK and Rågård, N and Kelsen, J and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Donor, patient age and exposure to antibiotics are associated with the outcome of faecal microbiota transplantation for recurrent Clostridioides difficile infection: A prospective cohort study.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.17642}, pmid = {37482926}, issn = {1365-2036}, support = {8056-00006B//Innovationsfonden/ ; R373-2021-1202//Lundbeckfonden/ ; NNF22OC0074080//Novo Nordisk Fonden/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably.

AIMS: To optimise the effectiveness of FMT for rCDI and validate determinants for effect.

METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8 weeks after their latest FMT.

RESULTS: 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65 years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faeces microbes nor standardising the processing improved outcomes.

CONCLUSION: FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes.

CLINICALTRIALS: gov (Study identifier: NCT03712722).}, } @article {pmid37482657, year = {2023}, author = {Wang, Z and Dan, W and Zhang, N and Fang, J and Yang, Y}, title = {Colorectal cancer and gut microbiota studies in China.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236364}, doi = {10.1080/19490976.2023.2236364}, pmid = {37482657}, issn = {1949-0984}, abstract = {Colorectal cancer (CRC) is the third most common malignant tumor worldwide. The incidence and mortality rates of CRC have been increasing in China, possibly due to economic development, lifestyle, and dietary changes. Evidence suggests that gut microbiota plays an essential role in the tumorigenesis of CRC. Gut dysbiosis, specific pathogenic microbes, metabolites, virulence factors, and microbial carcinogenic mechanisms contribute to the initiation and progression of CRC. Gut microbiota biomarkers have potential translational applications in CRC screening and early diagnosis. Gut microbiota-related interventions could improve anti-tumor therapy's efficacy and severe intestinal toxic effects. Chinese researchers have made many achievements in the relationship between gut microbiota and CRC, although some challenges remain. This review summarizes the current evidence from China on the role of gut microbiota in CRC, mainly including the gut microbiota characteristics, especially Fusobacterium nucleatum and Parvimonas micra, which have been identified to be enriched in CRC patients; microbial pathogens such as F. nucleatum and enterotoxigenic Bacteroides fragilis, and P. micra, which Chinese scientists have extensively studied; diagnostic biomarkers especially F. nucleatum; therapeutic effects, including microecological agents represented by certain Lactobacillus strains, fecal microbiota transplantation, and traditional Chinese medicines such as Berberine and Curcumin. More efforts should be focused on exploring the underlying mechanisms of microbial pathogenesis of CRC and providing novel gut microbiota-related therapeutic and preventive strategies.}, } @article {pmid37478946, year = {2023}, author = {Zhang, L and Kang, H and Zhang, W and Wang, J and Liu, Z and Jing, J and Han, L and Gao, A}, title = {Probiotics ameliorate benzene-induced systemic inflammation and hematopoietic toxicity by inhibiting Bacteroidaceae-mediated ferroptosis.}, journal = {The Science of the total environment}, volume = {899}, number = {}, pages = {165678}, doi = {10.1016/j.scitotenv.2023.165678}, pmid = {37478946}, issn = {1879-1026}, abstract = {The intestinal microbiota is associated with the development of benzene-induced hematopoietic toxicity. Modulation of intestinal homeostasis by probiotic supplementation has been considered an effective strategy to prevent adverse health effects. However, the role and mechanism of probiotics in benzene-induced hematopoietic toxicity are unclear. After 45 days of exposure, benzene caused bone marrow hematopoietic toxicity in mice. Furthermore, we found that benzene altered the intestinal barrier in mice, leading to an increase in the abundance of Bacteroidaceae and the activation of systemic inflammation. Interestingly, Fe[2+] accumulation, lipid peroxidation, and differential expression of ferroptosis proteins were observed in the intestinal tissues of benzene-exposed mice. After fecal microbiota transplantation, stool microbes from benzene-exposed mice led to the development of intestinal ferroptosis in recipient mice. In particular, oral probiotics significantly reversed elevated Bacteroidaceae and intestinal ferroptosis, ultimately improving benzene-induced hematopoietic damage. We further used the benzene metabolite 1,4-BQ to treat human normal colonic epithelial cells (NCM460) and intervened with the ferroptosis inhibitor liproxstatin-1 (Lip-1) to validate the relationship between intestinal ferroptosis and inflammation. The results showed that 1,4-BQ treatment resulted in increased intracellular ROS levels and abnormal expression of ferroptosis proteins and the inflammatory factors IL-5 and IL-13. However, the use of Lip-1 significantly inhibited oxidative stress, ferroptosis, and inflammation in NCM460 cells. This result suggested that ferroptosis might be involved in benzene-induced hematopoietic toxicity by mediating Th2-type systemic inflammation. Overall, these findings revealed a role for Bacteroidaceae-intestinal ferroptosis-inflammation in benzene-induced hematopoietic toxicity and highlighted that probiotics could be a promising strategy to prevent adverse hematologic outcomes.}, } @article {pmid37477511, year = {2023}, author = {Granger, MF and Kelly, M and Fortier, LC and Fournier, E and Côté-Gravel, J and Malouin, F and Valiquette, L and Lévesque, S}, title = {Chronic diarrhea caused by Klebsiella oxytoca toxin producer following antibiotic-associated hemorrhagic colitis: successful treatment by faecal microbiota transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciad436}, pmid = {37477511}, issn = {1537-6591}, abstract = {Klebsiella oxytoca is a Gram-negative bacterium found in faecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant.}, } @article {pmid37475750, year = {2023}, author = {Videvall, E and Bensch, HM and Engelbrecht, A and Cloete, S and Cornwallis, CK}, title = {Coprophagy rapidly matures juvenile gut microbiota in a precocial bird.}, journal = {Evolution letters}, volume = {7}, number = {4}, pages = {240-251}, pmid = {37475750}, issn = {2056-3744}, abstract = {Coprophagy is a behavior where animals consume feces, and has been observed across a wide range of species, including birds and mammals. The phenomenon is particularly prevalent in juveniles, but the reasons for this remain unclear. One hypothesis is that coprophagy enables offspring to acquire beneficial gut microbes that aid development. However, despite the potential importance of this behavior, studies investigating the effects in juveniles are rare. Here we experimentally test this idea by examining how ingestion of adult feces by ostrich chicks affects their gut microbiota development, growth, feeding behavior, pathogen abundance, and mortality. We conducted extensive longitudinal experiments for 8 weeks, repeated over 2 years. It involved 240 chicks, of which 128 were provided daily access to fresh fecal material from adults and 112 were simultaneously given a control treatment. Repeated measures, behavioral observations, and DNA metabarcoding of the microbial gut community, both prior to and over the course of the experiment, allowed us to evaluate multiple aspects of the behavior. The results show that coprophagy causes (a) marked shifts to the juvenile gut microbiota, including a major increase in diversity and rapid maturation of the microbial composition, (b) higher growth rates (fecal-supplemented chicks became 9.4% heavier at 8 weeks old), (c) changes to overall feeding behavior but no differences in feed intake, (d) lower abundance of a common gut pathogen (Clostridium colinum), and (e) lower mortality associated with gut disease. Together, our results suggest that the behavior of coprophagy in juveniles is highly beneficial and may have evolved to accelerate the development of gut microbiota.}, } @article {pmid37475473, 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 = {Gut microbes}, volume = {15}, number = {1}, pages = {2236750}, doi = {10.1080/19490976.2023.2236750}, pmid = {37475473}, issn = {1949-0984}, abstract = {The gastrointestinal microbiome plays a significant role in modulating numerous host processes, including metabolism. Prior studies show that when mice receive fecal transplants from obese donors on high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes, demonstrating the prominent role that gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, the impact of gut viruses on these phenotypes is understudied. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow over a 4-week study. By characterizing the gut bacterial biota via 16S rRNA amplicon sequencing and measuring mouse weights over time, we demonstrate that transplanted viruses affect the gut bacterial community, as well as weight gain/loss. Notably, mice fed chow but gavaged with HFD-derived viromes gained more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained less weight than their counterparts receiving HFD-derived viromes. Results were replicated in two independent experiments and phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Due to methodological limitations, we were unable to identify the specific bacterial strains responsible for respective phenotypic changes. This study confirms that virome-mediated perturbations can alter the fecal microbiome in vivo and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.}, } @article {pmid37474764, year = {2023}, author = {Chuang, C and Lee, KC and Wang, YP and Lee, PC and Chang, TE and Huang, YH and Lin, YT and Hou, MC}, title = {High carriage rate of extended-spectrum β-lactamase Enterobacterales and diarrheagenic Escherichia coli in healthy donor screening for fecal microbiota transplantation.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {37474764}, issn = {1435-4373}, support = {V107E-007-1 (108)//Taipei Veterans General Hospital/ ; V108E-007-1 (108)//Taipei Veterans General Hospital/ ; V108E-007-1 (109)//Taipei Veterans General Hospital/ ; V110E-002-1//Taipei Veterans General Hospital/ ; }, abstract = {The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs.}, } @article {pmid37474544, year = {2023}, author = {Castellini, G and Cassioli, E and Vitali, F and Rossi, E and Dani, C and Melani, G and Flaccomio, D and D'Andria, M and Mejia Monroy, M and Galli, A and Cavalieri, D and Ricca, V and Bartolucci, GL and De Filippo, C}, title = {Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11753}, pmid = {37474544}, issn = {2045-2322}, abstract = {Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.}, } @article {pmid37474412, year = {2023}, author = {Ribaldone, DG and Parisio, L and Variola, A and Bossa, F and Castiglione, F and Marzo, M and Piazza, N and Aratari, A and Savarino, EV and Bodini, G and Mastronardi, M and Micheli, F and Mazzuoli, S and Ascolani, M and Viganò, C and Cappello, M and Bezzio, C and Ciccocioppo, R and Scardino, G and Sarli, E and Pugliese, D and Scaldaferri, F and Napolitano, D and Todeschini, A and Geccherle, A and Colaci, N and Guerra, M and Annese, M and Testa, A and Caiazzo, A and Conforti, FS and Festa, S and Lorenzon, G and Marra, A and Magiotta, A and Baccini, F and Amato, A and Poshnjari, A and Vernero, M and Caprioli, F and Caviglia, GP and , }, title = {Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2023.07.011}, pmid = {37474412}, issn = {1878-3562}, abstract = {BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations.

AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission.

METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch.

RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%).

CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.}, } @article {pmid37473910, year = {2023}, author = {Zhao, Q and Chen, J and Wu, M and Yin, X and Jiang, Q and Gao, H and Zheng, H}, title = {Microbiota from healthy mice alleviates cognitive decline via reshaping the gut-brain metabolic axis in diabetic mice.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110638}, doi = {10.1016/j.cbi.2023.110638}, pmid = {37473910}, issn = {1872-7786}, abstract = {Diabetic cognitive decline has been associated with the gut microbial disorders, but its potential gut-brain axis mechanisms remain unclear. Herein we transplanted the gut microbiota from healthy mice into type 1 diabetic (T1D) mice and then investigated the effect of fecal microbiota transplantation (FMT) on cognitive function and the gut-brain metabolic axis. The results demonstrate that FMT from healthy mice effectively improved the learning and memory abilities in T1D mice, and significantly reduced neuroinflammation and neuron injury in the cortex and hippocampus. Moreover, FMT partly reversed the gut microbiota and gut-brain metabolic disorders, particularly glutamate metabolism. In vitro study, we found that glutamate notably decreased microglia activation and the expression levels of proinflammatory factor. Hence, our study suggests that glutamate serves as a key signal metabolite connecting the gut to brain and affects cognitive functions.}, } @article {pmid37471410, year = {2023}, author = {Qiu, B and Liang, J and Li, C}, title = {Effects of fecal microbiota transplantation in metabolic syndrome: A meta-analysis of randomized controlled trials.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0288718}, doi = {10.1371/journal.pone.0288718}, pmid = {37471410}, issn = {1932-6203}, abstract = {OBJECTIVE: The prevalence of obesity and type 2 diabetes is rapidly increasing worldwide, posing serious threats to human health. This study aimed to evaluate the role of FMT in the treatment of obesity and/or metabolic syndrome and its impact on clinically important parameters.

METHODS: We searched Medline, Embase, and Cochrane Library databases up to April 31, 2022 and further assessed articles that met the eligibility criteria. Mean differences and 95% confidence intervals were used to analyze continuous data. The I2 statistic was used to measure study heterogeneity. Univariate meta-regression or subgroup analyses were performed to explore the covariates that might contribute to heterogeneity. Potential publication bias was assessed using the Egger's test. We used the GRADEpro guideline development tool to assess the quality of the evidence.

RESULTS: Nine studies, comprising 303 participants, were included in the meta-analysis. In the short-term outcomes (<6 weeks after FMT), compared with the placebo group, patients in the FMT group had lower FBG (MD = -0.12 mmol/L, 95% Cl: -0.23, -0.01), HbA1c (MD = -0.37 mmol/mol, 95%Cl: -0.73, -0.01), and insulin levels (MD = -24.77 mmol/L, 95% Cl: -37.60, -11.94), and higher HDL cholesterol levels (MD = 0.07 mmol/L, 95% Cl: 0.02, 0.11).

CONCLUSIONS: FMT, as an adjunctive therapy, does not produce any serious adverse effects and may be useful in the treatment of metabolic syndrome, especially in improving HbA1c, insulin sensitivity, and HDL cholesterol. However, there was no significant difference between the FMT group and the placebo group in terms of weight reduction.}, } @article {pmid37470727, year = {2023}, author = {Wang, W and Cui, B and Nie, Y and Sun, L and Zhang, F}, title = {Radiation injury and gut microbiota-based treatment.}, journal = {Protein & cell}, volume = {}, number = {}, pages = {}, doi = {10.1093/procel/pwad044}, pmid = {37470727}, issn = {1674-8018}, abstract = {The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and•organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes ten common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.}, } @article {pmid37469740, year = {2023}, author = {Singh, SV and Ganguly, R and Jaiswal, K and Yadav, AK and Kumar, R and Pandey, AK}, title = {Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review.}, journal = {World journal of clinical cases}, volume = {11}, number = {19}, pages = {4458-4476}, pmid = {37469740}, issn = {2307-8960}, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.}, } @article {pmid37469721, year = {2023}, author = {da Ponte Neto, AM and Clemente, ACO and Rosa, PW and Ribeiro, IB and Funari, MP and Nunes, GC and Moreira, L and Sparvoli, LG and Cortez, R and Taddei, CR and Mancini, MC and de Moura, EGH}, title = {Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial.}, journal = {World journal of clinical cases}, volume = {11}, number = {19}, pages = {4612-4624}, pmid = {37469721}, issn = {2307-8960}, abstract = {BACKGROUND: Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease.

AIM: To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome.

METHODS: This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota.

RESULTS: There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated.

CONCLUSION: There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.}, } @article {pmid37469558, year = {2023}, author = {Tian, E and Wang, F and Zhao, L and Sun, Y and Yang, J}, title = {The pathogenic role of intestinal flora metabolites in diabetic nephropathy.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1231621}, pmid = {37469558}, issn = {1664-042X}, abstract = {With the increasing incidence of diabetes, diabetic kidney disease has become a major cause of chronic kidney disease. The role of the gut microbiota in diabetes and its related complications have been extensively investigated; the modulatory effect of the gut microbiota on the host depends on several gut microbial metabolites, particularly short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. In this review, we focused on the evidence related to the pathogenic role of each of the gut microbial metabolites in diabetic nephropathy. The main novel therapies targeting the gut microbiota include probiotics, dietary prebiotics, synbiotic supplements, and faecal microbiota transplants, although there is no standard treatment principle. Further research is therefore needed to elucidate the link between gut microbes and diabetic nephropathy, and more therapeutic targets should be explored to treat diabetic nephropathy with dysbiosis of the gut microbes.}, } @article {pmid37469017, year = {2023}, author = {Tian, H and Cui, J and Ye, C and Zhao, J and Yang, B and Xu, Y and Ji, S and Wang, L and Lv, X and Ma, C and Zhou, S and Li, N and Wang, X and Qin, H and Chen, Q}, title = {Depletion of butyrate-producing microbes of the Firmicutes predicts nonresponse to FMT therapy in patients with recurrent Clostridium difficile infection.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236362}, doi = {10.1080/19490976.2023.2236362}, pmid = {37469017}, issn = {1949-0984}, abstract = {Approximately 10% of individuals diagnosed with Clostridium difficile infection (CDI) show the resistance to fecal microbiota transplantation (FMT), with the underlying mechanisms remaining elusive. Deciphering the intricate microbiome profile within this particular subset of FMT-refractory patients via clinical FMT investigations assumes paramount importance, as it holds the key to designing targeted therapeutic interventions tailored for CDI, particularly recurrent CDI (rCDI). A cohort of twenty-three patients afflicted with rCDI, exhibiting congruent clinical baselines, was meticulously selected for FMT. Rigorous screening of thousands of healthy individuals identified ten FMT donors who met stringent health standards, while a total of 171 stool samples were collected to serve as healthy controls. To assess the influence of microbiome dynamics on FMT efficacy, fecal samples were collected from four donors over a continuous period of twenty-five weeks. After FMT treatment, seven individuals exhibited an inadequate response to FMT. These non-remission patients displayed a significant reduction in α-diversity indexes. Meanwhile, prior to FMT, the abundance of key butyrate-producing Firmicutes bacteria, including Christensenellaceae_R_7_group, Ruminococcaceae_unclassified, Coprococcus_2, Fusicatenibacter, Oscillospira, and Roseburia, were depleted in non-remission patients. Moreover, Burkholderiales_unclassified, Coprococcus_2, and Oscillospira failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of Veillonella prior to treatment, whereas its depletion was commonly observed in non-remission individuals. Genera interactions in lower effectiveness FMT donors were more similar to those in non-remission patients, and Burkholderiales_unclassified, Coprococcus_2, and Oscillospira were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of Veillonella, consistent with their poor prognosis after FMT. FMT non-remission rCDI patients exhibited distinct characteristics that hindered the colonization of beneficial butyrate-producing Firmicutes microbes. These findings hold promise in advancing the precision of FMT therapy for rCDI patients.}, } @article {pmid37467715, year = {2023}, author = {Jarosch, S and Köhlen, J and Ghimire, S and Orberg, ET and Hammel, M and Gaag, D and Evert, M and Janssen, KP and Hiergeist, A and Gessner, A and Weber, D and Meedt, E and Poeck, H and D'Ippolito, E and Holler, E and Busch, DH}, title = {Multimodal immune cell phenotyping in GI biopsies reveals microbiome-related T cell modulations in human GvHD.}, journal = {Cell reports. Medicine}, volume = {4}, number = {7}, pages = {101125}, doi = {10.1016/j.xcrm.2023.101125}, pmid = {37467715}, issn = {2666-3791}, abstract = {Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining disease severity are not well defined yet. By combining multiplexed tissue imaging and single-cell RNA sequencing on gastrointestinal biopsies from aHSCT-treated individuals with fecal microbiome analysis, we link high microbiome diversity and the abundance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells (Tregs). Furthermore, aGvHD severity strongly associates with the clonal expansion of mainly CD8 T cells, which we find distributed over anatomically distant regions of the gut, persistent over time, and inversely correlated with the presence of suppressive Tregs. Overall, our study highlights the pathophysiological importance of expanded CD8 T cell clones in the progression of aGvHD toward more severe clinical manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.}, } @article {pmid37464825, year = {2023}, author = {Moghadam, MT and Ramírez-Coronel, AA and Darijani, S and Akbarizadeh, MR and Naderifar, M and Soltaninejad, S and Shahbazi, S and Dousari, AS and Mojtahedi, A and Akhavan-Sigari, R}, title = {Perturbations in microbiota composition as a novel mediator in neuropsychiatric, neurological and mental disorders: Preventive and therapeutic complementary therapies to balance the change.}, journal = {Current Alzheimer research}, volume = {}, number = {}, pages = {}, doi = {10.2174/1567205020666230718160914}, pmid = {37464825}, issn = {1875-5828}, abstract = {Although microbiology and neurology are separate disciplines, they are linked to some infectious and neurological diseases. Today, microbiome is considered as one of the biomarkers of health by many researchers. This has led to the association of microbiome changes with many neurological diseases. The natural microbiota has many beneficial properties. If disrupted and altered, it can lead to irreversible complications and many neurological diseases. Therefore, according to previous studies, some preventive and therapeutic complementary therapies can prevent or restore microbiome dysbiosis and inflammation in the nervous system. With our current perception of the microbiological basis for different neurological disorders, both aspects of drug treatment and control of perturbations of the microbiome should be considered, and targeting them simultaneously will likely help to attain favorable results.}, } @article {pmid37460073, year = {2023}, author = {Fang, J and Li, YX and Luo, HY and Zhang, WH and Chan, KC and Chan, YM and Chen, HB and Zhao, ZZ and Li, SL and Dong, CX and Xu, J}, title = {Impacts of sulfur fumigation on the chemistry and immunomodulatory activity of polysaccharides in ginseng.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {125843}, doi = {10.1016/j.ijbiomac.2023.125843}, pmid = {37460073}, issn = {1879-0003}, abstract = {Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.}, } @article {pmid37458581, year = {2023}, author = {Montalto, M and Gallo, A and Agnitelli, MC and Pellegrino, S and Lipari, A and Pero, E and Covino, M and Landi, F and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in frail and very old patients.}, journal = {Journal of the American Geriatrics Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgs.18500}, pmid = {37458581}, issn = {1532-5415}, support = {//Italian Ministry of Health-Ricerca Corrente 2023 and European Union-Next Generation EU (AGE-IT)/ ; }, abstract = {BACKGROUND: Older age is a well-known risk factor for recurrent and severe Clostridioides difficile infection (CDI). Fecal microbiota transplantation (FMT) is widely recognized as an effective and safe therapeutic option for the treatment of recurrent CDI (rCDI). However, the efficacy and safety of FMT for rCDI in very old patients are uncertain. This study evaluated the efficacy and safety of FMT in a group of very old subjects with rCDI, and the reliability of overall comorbidity and frailty assessment for identifying patients at higher risk of worse clinical outcomes.

METHODS: This is a retrospective single-center study including patients ≥85 years undergoing FMT for rCDI between 2014 and 2022. Primary outcomes included efficacy of FMT, defined as cure of CDI at 8 week-follow-up, and safety evaluation. At baseline, comorbidity was measured with the Charlson Comorbidity Index (CCI). Frailty was measured with the Clinical Frailty Scale (CFS).

RESULTS: Overall, 43 patients with a median age of 88 years underwent FMT by colonoscopy in the study period. The rate of first FMT success was 77%. Five of the 10 patients who failed the first FMT infusion were cured after repeat FMT, with an overall efficacy of 88%. In patients with successful treatment, the CFS was significantly lower compared to those who failed the FMT or underwent repeat FMT (p < 0.01 for both). Mild adverse events occurred in 11 patients (25%). One death, not related to FMT or rCDI, occurred within 7 days from the first procedure.

CONCLUSIONS: FMT is effective and safe in very old patients. Frailty and high comorbidity do not limit use of FMT in these patients. Frailty assessment has potential to better identify patients at higher risk of worse outcomes or for repeat treatment with FMT.}, } @article {pmid37457968, year = {2023}, author = {Fatani, AMN and Suh, JH and Auger, J and Alabasi, KM and Wang, Y and Segal, MS and Dahl, WJ}, title = {Pea hull fiber supplementation does not modulate uremic metabolites in adults receiving hemodialysis: a randomized, double-blind, controlled trial.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1179295}, pmid = {37457968}, issn = {2296-861X}, abstract = {BACKGROUND: Fiber is a potential therapeutic to suppress microbiota-generated uremic molecules. This study aimed to determine if fiber supplementation decreased serum levels of uremic molecules through the modulation of gut microbiota in adults undergoing hemodialysis.

METHODS: A randomized, double-blinded, controlled crossover study was conducted. Following a 1-week baseline, participants consumed muffins with added pea hull fiber (PHF) (15 g/d) and control muffins daily, each for 4 weeks, separated by a 4-week washout. Blood and stool samples were collected per period. Serum p-cresyl sulfate (PCS), indoxyl sulfate (IS), phenylacetylglutamine (PAG), and trimethylamine N-oxide (TMAO) were quantified by LC-MS/MS, and fecal microbiota profiled by 16S rRNA gene amplicon sequencing and specific taxa of interest by qPCR. QIIME 2 sample-classifier was used to discover unique microbiota profiles due to the consumption of PHF.

RESULTS: Intake of PHF contributed an additional 9 g/d of dietary fiber to the subjects' diet due to compliance. No significant changes from baseline were observed in serum PCS, IS, PAG, or TMAO, or for the relative quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium, or Roseburia, taxa considered health-enhancing. Dietary protein intake and IS (r = -0.5, p = 0.05) and slow transit stool form and PCS (r = 0.7, p < 0.01) were significantly correlated at baseline. PHF and control periods were not differentiated; however, using machine learning, taxa most distinguishing the microbiota composition during the PHF periods compared to usual diet alone were enriched Gemmiger, Collinsella, and depleted Lactobacillus, Ruminococcus, Coprococcus, and Mogibacteriaceae.

CONCLUSION: PHF supplementation did not mitigate serum levels of targeted microbial-generated uremic molecules. Given the high cellulose content, which may be resistant to fermentation, PHF may not exert sufficient effects on microbiota composition to modulate its activity at the dose consumed.}, } @article {pmid37457967, year = {2023}, author = {Cao, C and Shi, M and Wang, X and Yao, Y and Zeng, R}, title = {Effects of probiotics on non-alcoholic fatty liver disease: a review of human clinical trials.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1155306}, pmid = {37457967}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a global public health issue, of which the prevalence is about 25% worldwide. The incidence of NAFLD is increasing in patients with obesity, type 2 diabetes (T2DM) and the metabolic syndrome. The crosstalk between gut microbiota and metabolism-related diseases has been raised great concern. Patients with NAPLD were observed with disruption of gut microbiota. Several researches showed that gut microbiota was the determination in the progression of NAFLD by the experiments using fecal microbiota transplants. The application of probiotics, as one of the most important strategies for the regulation of gut microbiota disorder, have been explored whether it is beneficial to gut-related diseases of intestine-distal organs. Some probiotics were showed to improve the liver parameters and phenotype in patients with NAFLD. The oral intake of them might become the effective management for the prevention and treatment of NAFLD. In this review, we summarized the human clinical trials focusing on the effects of probiotics on NAFLD to give some evidential reference for the administration of NAFLD.}, } @article {pmid37454252, year = {2023}, author = {Jun, Z and Junhua, W and Xiaobing, LI and Chenyi, W and Fangjun, LI and Yanni, L and Hao, C and Meiying, S}, title = {Efficacy of Heshouwu () on gut mircobiota in mice with autoimmune encephalomyelitis.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {43}, number = {4}, pages = {676-685}, pmid = {37454252}, issn = {2589-451X}, support = {82101419//National Natural Science Foundation of China: Role and Mechanism of Akkermansia-Mediated Activation of Microglia NLRP3 Inflammasome in Multiple Sclerosis/ ; 20212BAB216024//Jiangxi Provincial Natural Science Foundation: the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Change in EAE Mice/ ; 2021B660//Jiangxi Science and Technology Project of Chinese Medicine: Study on the Role and Mechanism of CGAS-STING Signaling Pathway in Microglia Mediated by Rhodiola Sachalinensis in Multiple Sclerosis/ ; 2022B1007//Jiangxi Science and Technology Project of Chinese Medicine: Study on the Role and Mechanism of CGAS-STING Signaling Pathway in Microglia Mediated by Rhodiola Sachalinensis in Multiple Sclerosis/ ; 202210392//Jiangxi Science and Technology Program of Health Commission: the Role and Mechanism of Intestinal Flora Changes in Mediating the Activation of NLRP3 Inflammasome in Microglia in Multiple Sclerosis/ ; GJJ200215//Science and Technology Research Project of Jiangxi Education: Study on the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Changes in EAE Mice/ ; YFYPY202021//Scientific Research and Development Project of the First Affiliated Hospital of Nanchang University: Effects of Exercise Training on Intestinal Flora of Multiple Sclerosis Model Rats and Its Mechanism/ ; }, mesh = {Mice ; Animals ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; RNA, Ribosomal, 16S ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy/genetics ; Spinal Cord/pathology ; *Encephalomyelitis/pathology ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: To learn the mechanisms between gut microbiome and the autoimmunity benefits on Traditional Chinese Medicine (TCM) in central nervous system (CNS), we investigated the neuro-protection effects and gut mircobiota changes of Heshouwu () on experimental autoimmune encepha-lomyelitis (EAE), an animal model of multiple sclerosis (MS).

METHODS: Mice were randomly divided into four groups: EAE mice (control phosphate-buffered saline group), 50 mg·kg·d Heshouwu ()-treated EAE mice, 100 mg·kg·d Heshouwu ()-treated EAE mice, and 200 mg·kg·d Heshouwu ()-treated EAE mice. The spinal cords were stained with hematoxylin and eosin (HE) and luxol fast blue for evaluating inflammatory infiltration and demyelination. The percentages of granulocyte macrophage-colony stimulating factor (GM-CSF)+CD4+, interleukin 17 (IL-17)+CD4+, Foxp3 CD4+, and interferon-γ (IFN-γ)+CD4+ T cells in the inguinal lymph nodes (LNs) and brain were determined by flow cytometry analysis. 16S rRNA gene sequencing was employed to analyze the changes in gut microbiota.

RESULTS: We found that Heshouwu () alleviated the disease severity and neuropathology of EAE as evaluated by clinical and histopathologyical scores. Heshouwu () increased the diversity and abundance of the gut microbiota, and decreased / ratio (F/B ratio). Heshouwu () also decreased the concentrations of IL-10, and IL-21 and increase the levels of GM-CSF, IL-17A, IL-17F and IL-22 in serum of EAE mice. Moreover, Heshouwu () modulated the T cell responses by inhibiting Th17 cells and restoring Treg cells in the small intestine lymphoid tissues and inguinal lymph nodes. Microbiota-depleted mice receiving Heshouwu ()-treated fecal microbiota trans-plantation had lower disease severity, neuropathology scores and alleviation of Th17/Treg imbalance compared to ad libitum group.

CONCLUSIONS: Our findings suggested that the vital neuro-protection role of Heshouwu () (TCM) in immunomodulation effects partly by regulations of gut microbiome.}, } @article {pmid37454113, year = {2023}, author = {Zheng, H and Zhao, Q and Chen, J and Lu, J and Li, Y and Gao, H}, title = {Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {166}, pmid = {37454113}, issn = {1742-2094}, support = {22074106//National Natural Science Foundation of China/ ; 21974096//National Natural Science Foundation of China/ ; }, mesh = {Male ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Neuroinflammatory Diseases ; RNA, Ribosomal, 16S/genetics ; Quality of Life ; *Cognitive Dysfunction ; *Pneumonia ; *Respiratory Distress Syndrome/microbiology ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients' quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive.

METHODS: Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte and neuron in the cortex and hippocampus were examined via immunofluorescent staining.

RESULTS: We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide (LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons.

CONCLUSIONS: Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice.}, } @article {pmid37453856, year = {2023}, author = {Jiang, L and Xu, J and Cheng, SY and Wang, Y and Cai, W}, title = {The gut microbiome and intestinal failure-associated liver disease.}, journal = {Hepatobiliary & pancreatic diseases international : HBPD INT}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hbpd.2023.07.002}, pmid = {37453856}, issn = {1499-3872}, abstract = {Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, and cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.}, } @article {pmid37451630, year = {2023}, author = {Zhang, X and Cremers, N and Hendrickx, S and Debing, Y and Roskams, T and Coelmont, L and Neyts, J and Kaptein, SJF}, title = {Establishment of a robust rat hepatitis E virus fecal-oral infection model and validation for antiviral studies.}, journal = {Antiviral research}, volume = {216}, number = {}, pages = {105670}, doi = {10.1016/j.antiviral.2023.105670}, pmid = {37451630}, issn = {1872-9096}, abstract = {The hepatitis E virus (HEV) is a major cause of hepatitis, with an estimated 3.3 million symptomatic cases annually. There is no HEV-specific treatment besides the off-label use of ribavirin and a vaccine is only available in China and Pakistan. To aid the development of therapeutic and preventive strategies, there is a need for convenient HEV infection models in small laboratory animals. To this end, we make use of the rat hepatitis E virus. Human infections with this virus have been reported in recent years, making it a relevant pathogen for the establishment of a small animal infection model. We here report that oral gavage of a feces suspension, containing a pre-defined viral RNA load, results in a reproducible synchronized infection in athymic nude rats. This route of administration mimics fecal-oral transmission in a standardized fashion. The suitability of the model to study the effect of antiviral drugs was assessed by using ribavirin, which significantly reduced viral loads in the feces, liver, and other tissues.}, } @article {pmid37451270, year = {2023}, author = {Yang, J and Yang, X and Wu, G and Huang, F and Shi, X and Wei, W and Zhang, Y and Zhang, H and Cheng, L and Yu, L and Shang, J and Lv, Y and Wang, X and Zhai, R and Li, P and Cui, B and Fang, Y and Deng, X and Tang, S and Wang, L and Yuan, Q and Zhao, L and Zhang, F and Zhang, C and Yuan, H}, title = {Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2023.06.010}, pmid = {37451270}, issn = {1932-7420}, abstract = {The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.}, } @article {pmid37450947, year = {2023}, author = {Zaman, S and Akingboye, A and Mohamedahmed, AY and Peterknecht, E and Bhattacharya, P and El-Asrag, ME and Iqbal, TH and Quraishi, MN and Beggs, AD}, title = {Faecal microbiota transplantation (FMT) in the treatment of chronic refractory pouchitis: A systematic review and meta-analysis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjad120}, pmid = {37450947}, issn = {1876-4479}, abstract = {BACKGROUND: The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation (FMT) in the treatment of chronic pouchitis.

METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews (CENTRAL), clinical trials.gov, ScienceDirect, and VHL (virtual health library). The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life and changes in the gut microbiome.

RESULTS: Seven observational cohort studies/case series and two randomised controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied amongst the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting adverse events were reported, and the treatment was well tolerated with a good short- and long-term safety profile.Successful FMT engraftment in recipients varied and on average microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species suggestive of a 'healthier' pouch microbiota were observed following treatment with FMT.

CONCLUSION: The evidence for FMT in the treatment of chronic pouchitis is sparse which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate but the treatment is well tolerated with a good safety profile. This review emphasises the need for rationally designed well powered randomised placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.}, } @article {pmid37450589, year = {2023}, author = {Shi, B and Zhang, X and Song, Z and Dai, Z and Luo, K and Chen, B and Zhou, Z and Cui, Y and Feng, B and Zhu, Z and Zheng, J and Zhang, H and He, X}, title = {Targeting gut microbiota-derived kynurenine to predict and protect the remodeling of the pressure-overloaded young heart.}, journal = {Science advances}, volume = {9}, number = {28}, pages = {eadg7417}, doi = {10.1126/sciadv.adg7417}, pmid = {37450589}, issn = {2375-2548}, abstract = {Pressure-overloaded left ventricular remodeling in young population is progressive and readily degenerate into heart failure. The aims of this study were to identify a plasma metabolite that predicts and is mechanistically linked to the disease. Untargeted metabolomics determined elevated plasma kynurenine (Kyn) in both the patient cohorts and the mice model, which was correlated with remodeling parameters. In vitro and in vivo evidence, combined with single-nucleus RNA sequencing (snRNA-seq), demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by activating aryl hydrocarbon receptors (AHR) to up-regulate hypertrophy- and fibrosis-related genes. Shotgun metagenomics and fecal microbiota transplantation revealed the existence of the altered gut microbiota-Kyn relationship. Supplementation of selected microbes reconstructed the gut microbiota, reduced plasma Kyn, and alleviated ventricular remodeling. Our data collectively discovered a gut microbiota-derived metabolite to activate AHR and its gene targets in remodeling young heart, a process that could be prevented by specific gut microbiota modulation.}, } @article {pmid37449731, year = {2023}, author = {}, title = {Fecal Microbiota Transplantation plus Anti-PD-1 Is Safe in a First-line Setting.}, journal = {Cancer discovery}, volume = {}, number = {}, pages = {OF1}, doi = {10.1158/2159-8290.CD-RW2023-109}, pmid = {37449731}, issn = {2159-8290}, abstract = {Fecal microbiota transplantation combined with anti-PD-1 is safe in melanoma in the first-line setting.}, } @article {pmid37446647, year = {2023}, author = {Yan, X and Li, J and Wu, D}, title = {The Role of Short-Chain Fatty Acids in Acute Pancreatitis.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {13}, pages = {}, doi = {10.3390/molecules28134985}, pmid = {37446647}, issn = {1420-3049}, support = {32170788//National Natural Science Foundation of China/ ; 2022-PUMCH-B-023//National High Level Hospital Clinical Research Funding/ ; ZK108000//National Key Clinical Specialty Construction Project/ ; 7232123//Beijing Natural Science Foundation/ ; }, abstract = {Acute pancreatitis (AP) is a digestive emergency and can develop into a systematic illness. The role of the gut in the progression and deterioration of AP has drawn much attention from researchers, and areas of interest include dysbiosis of the intestinal flora, weakened intestinal barrier function, and bacterial and endotoxin translocation. Short-chain fatty acids (SCFAs), as one of the metabolites of gut microbiota, have been proven to be depleted in AP patients. SCFAs help restore gut homeostasis by rebuilding gut flora, stabilizing the intestinal epithelial barrier, and regulating inflammation. SCFAs can also suppress systematic inflammatory responses, improve the injured pancreas, and prevent and protect other organ dysfunctions. Based on multiple beneficial effects, increasing SCFAs is an essential idea of gut protective treatment in AP. Specific strategies include the direct use of butyrate or indirect supplementation through fiber, pre/pro/synbiotics, or fecal microbiota transplantation as a promising adjective therapy to enteral nutrition.}, } @article {pmid37446182, year = {2023}, author = {Zhu, M and Song, Y and Xu, Y and Xu, H}, title = {Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, doi = {10.3390/ijms241311004}, pmid = {37446182}, issn = {1422-0067}, support = {U1902213//the NSFC-Joint Foundation of Yunnan Province/ ; 2020B1111110003//the Guangdong Province Key Area R&D Program of China/ ; }, abstract = {Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn's disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota.}, } @article {pmid37444223, year = {2023}, author = {Ang, WS and Law, JW and Letchumanan, V and Hong, KW and Wong, SH and Ab Mutalib, NS and Chan, KG and Lee, LH and Tan, LT}, title = {A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {13}, pages = {}, doi = {10.3390/foods12132485}, pmid = {37444223}, issn = {2304-8158}, support = {ECR-000039//Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia/ ; }, abstract = {A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.}, } @article {pmid37443082, year = {2023}, author = {Zhang, H and Zheng, L and Li, C and Jing, J and Li, Z and Sun, S and Xue, T and Zhang, K and Xue, M and Cao, C and Ouyang, L and Qian, Z and Xu, R and He, Z and Ma, R and Chen, L and Yao, B}, title = {Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.}, journal = {Journal of ovarian research}, volume = {16}, number = {1}, pages = {138}, pmid = {37443082}, issn = {1757-2215}, support = {82271687//National Natural Science Foundation of China/ ; 82274651//National Natural Science Foundation of China/ ; BE2022712//Jiangsu Provincial Key Research and Development Program/ ; ZD2022004//Key Medical Research Projects of Jiangsu Provincial Health Commission/ ; }, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota.

METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated.

RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues.

CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.}, } @article {pmid37442498, year = {2023}, author = {Keubler, LM and Talbot, SR and Bleich, A and Boyle, EC}, title = {Systematic review and meta-analysis of the effect of fecal microbiota transplantation on behavior in animals.}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {105316}, doi = {10.1016/j.neubiorev.2023.105316}, pmid = {37442498}, issn = {1873-7528}, abstract = {The bi-directional interaction between gut microbiota and the central nervous system has been coined the gut microbiota-brain axis. Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient. Preclinical FMT experiments are essential to prove causality in the context of the gut microbiota-brain axis. In this systematic review, we assess the body of evidence related to the ability of FMT to modulate an animal's behavior. Accordingly, we provide a detailed summary of the use of FMT in behavior-related animal studies, an extensive risk of bias analysis, and a meta-analysis of the overall effect of FMT on behavioral outcome measures in 64 studies, representing 4889 animals. The resulting meta-analysis revealed FMT was effective at changing animal behavior, thereby substantiating evidence for the gut microbiota-brain axis. However, our study also highlights an urgent need for methodological safeguards within this research field to reduce the risk of bias and improve the internal validity of future studies.}, } @article {pmid37442219, year = {2023}, author = {Qi, D and Zou, S and Lu, D and Pei, X and Huang, S and Huang, DL and Liu, J and Si, H and Li, Z}, title = {Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {109573}, doi = {10.1016/j.exer.2023.109573}, pmid = {37442219}, issn = {1096-0007}, abstract = {The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.}, } @article {pmid37441951, year = {2023}, author = {Zhang, Y and Hou, B and Liu, T and Wu, Y and Wang, Z}, title = {Probiotics improve polystyrene microplastics-induced male reproductive toxicity in mice by alleviating inflammatory response.}, journal = {Ecotoxicology and environmental safety}, volume = {263}, number = {}, pages = {115248}, doi = {10.1016/j.ecoenv.2023.115248}, pmid = {37441951}, issn = {1090-2414}, abstract = {As a new type of environmental pollutant, microplastics have been garnered increasing attention, especially in regard to their effects on the reproductive system. However, researchers have yet to report whether prevention and treatment measures exist for reproductive injury caused by microplastics. The aim of this study was therefore to explore the mechanism of spermatogenic injury induced by polystyrene microplastics (PS-MPs) and the intervention effect of probiotics based on the gut microbiota-testis axis. Mice were orally exposed for 35 days to 5 µm of PS-MPs with a gavage dose was 0.1 mg/day, and the intervention group was given probiotics (Lactobacillus, Bifidobacterium longum, and Enterococcus) orally. Fecal samples were then subjected to 16 S rRNA sequencing analysis, and sperm motion was analyzed by a Hamilton-Thorne Sperm analyzer. The results showed that PS-MPs exposed mice had significant spermatogenic dysfunction and testicular inflammation. In addition, the intestinal microbial structure of exposed mice changed significantly; the abundance of Lactobacillus decreased, and the abundance of Prevotella increased. Furthermore, with fecal microbiota transplantation, the recipient mice showed a significant decrease in sperm quality. However, probiotics supplementation helped inhibit the activation of IL-17A signaling driven by gut microbes, thereby alleviating the inflammatory response and improving sperm quality decline caused by PS-MPs. These results may provide a scientific basis for further understanding of the mechanism of male reproductive damage caused by environmental pollutants such as microplastics and for novel reproductive damage intervention measures.}, } @article {pmid37441494, year = {2023}, author = {Neri-Rosario, D and Martínez-López, YE and Esquivel-Hernández, DA and Sánchez-Castañeda, JP and Padron-Manrique, C and Vázquez-Jiménez, A and Giron-Villalobos, D and Resendis-Antonio, O}, title = {Dysbiosis signatures of gut microbiota and the progression of type 2 diabetes: a machine learning approach in a Mexican cohort.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1170459}, pmid = {37441494}, issn = {1664-2392}, abstract = {INTRODUCTION: The gut microbiota (GM) dysbiosis is one of the causal factors for the progression of different chronic metabolic diseases, including type 2 diabetes mellitus (T2D). Understanding the basis that laid this association may lead to developing new therapeutic strategies for preventing and treating T2D, such as probiotics, prebiotics, and fecal microbiota transplants. It may also help identify potential early detection biomarkers and develop personalized interventions based on an individual's gut microbiota profile. Here, we explore how supervised Machine Learning (ML) methods help to distinguish taxa for individuals with prediabetes (prediabetes) or T2D.

METHODS: To this aim, we analyzed the GM profile (16s rRNA gene sequencing) in a cohort of 410 Mexican naïve patients stratified into normoglycemic, prediabetes, and T2D individuals. Then, we compared six different ML algorithms and found that Random Forest had the highest predictive performance in classifying T2D and prediabetes patients versus controls.

RESULTS: We identified a set of taxa for predicting patients with T2D compared to normoglycemic individuals, including Allisonella, Slackia, Ruminococus_2, Megaspgaera, Escherichia/Shigella, and Prevotella, among them. Besides, we concluded that Anaerostipes, Intestinibacter, Prevotella_9, Blautia, Granulicatella, and Veillonella were the relevant genus in patients with prediabetes compared to normoglycemic subjects.

DISCUSSION: These findings allow us to postulate that GM is a distinctive signature in prediabetes and T2D patients during the development and progression of the disease. Our study highlights the role of GM and opens a window toward the rational design of new preventive and personalized strategies against the control of this disease.}, } @article {pmid37441065, year = {2023}, author = {Yang, JW and Wan, S and Li, KP and Chen, SY and Yang, L}, title = {Gut and urinary microbiota: the causes and potential treatment measures of renal cell carcinoma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1188520}, pmid = {37441065}, issn = {1664-3224}, abstract = {Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC.}, } @article {pmid37440825, year = {2023}, author = {Pei, B and Ma, X and Wu, N and Wang, C and Yang, W}, title = {Effect of microbiome group on immune checkpoint inhibitors in treatment of gastrointestinal tumors.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {35}, number = {3}, pages = {252-265}, pmid = {37440825}, issn = {1000-9604}, abstract = {In recent years, immune checkpoint blockade (ICB) therapy has become an important treatment strategy for gastrointestinal tumors, however, it only benefits about 1/3 of patients. Since the microbiome has been shown to play an important role in the human body for a long time, a growing number of studies are focusing on its relationship to ICB therapy in cancer, specifically how intestinal microbes affect the efficacy of immune checkpoint inhibitors (ICIs) therapy in patients. On this basis, probiotic interventions, fecal microbiota transplantation (FMT), dietary interventions, and other methods which improve or maintain the structure of the intestinal flora have attracted widespread attention. This article discusses the four aspects of the microbiome, ICB, combined treatment of gastrointestinal tumors, and regulation of gut microbiome. Particularly, the discussion focuses on the contribution of probiotic intervention in improving the therapeutic effect of ICIs to prolong the survival time of patients and reduce the severity of immune-related adverse effects (irAEs).}, } @article {pmid37440367, year = {2023}, author = {Muralitharan, RR and Snelson, M and Meric, G and Coughlan, MT and Marques, FZ}, title = {Guidelines for Microbiome Studies in Renal Physiology.}, journal = {American journal of physiology. Renal physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajprenal.00072.2023}, pmid = {37440367}, issn = {1522-1466}, support = {105663,106698//National Heart Foundation of Australia (Heart Foundation)/ ; GNT2017382//DHAC | National Health and Medical Research Council (NHMRC)/ ; N/A//Sylvia and Charles Viertel Charitable Foundation (SCVCF)/ ; }, abstract = {Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and faecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animal and clinical studies assessing renal function, many which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatisation, baseline microbiota and its normalisation, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardising study designs, methods and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.}, } @article {pmid37439281, year = {2023}, author = {Mo, X and Shen, L and Cheng, R and Wang, P and Wen, L and Sun, Y and Wang, Q and Chen, J and Lin, S and Liao, Y and Yang, W and Yan, H and Liu, L}, title = {Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcsm.13294}, pmid = {37439281}, issn = {2190-6009}, support = {82230112//National Natural Science Foundation of China/ ; AF2019001-3//Angel Nutrition Research Fund/ ; }, abstract = {BACKGROUND: Gut microbiota plays a key role in the development of sarcopenia via the 'gut-muscle' axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia.

METHODS: The fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.

RESULTS: As evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross-section area of myofibres (both P < 0.001), fast-switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites-Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites-Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin-2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-induced alterations of gut microbiota and metabolites might be closely related to mitochondria-related genes and sarcopenia-related phenotypes.

CONCLUSIONS: yFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age-related sarcopenia.}, } @article {pmid37439168, year = {2023}, author = {Fan, J and Sun, Y and Liang, B and Zhang, X and Xiao, C and Huang, Z}, title = {[Role of gut microbiota in perioperative neurocognitive disorders after cardiopulmonary bypass surgery in rats with humanized gut flora].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {43}, number = {6}, pages = {964-969}, doi = {10.12122/j.issn.1673-4254.2023.06.11}, pmid = {37439168}, issn = {1673-4254}, abstract = {OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND).

METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test.

RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05).

CONCLUSION: In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.}, } @article {pmid37433041, year = {2023}, author = {Wu, H and Leng, X and Liu, Q and Mao, T and Jiang, T and Liu, Y and Li, F and Cao, C and Fan, J and Chen, L and Chen, Y and Yao, Q and Lu, S and Liang, R and Hu, L and Liu, M and Wan, Y and Li, Z and Peng, J and Luo, Q and Zhou, H and Yin, J and Xu, K and Lan, M and Peng, X and Lan, H and Li, G and Han, Y and Zhang, X and Xiao, ZJ and Lang, J and Wang, G and Xu, C}, title = {Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.}, journal = {Cancer research}, volume = {}, number = {}, pages = {}, doi = {10.1158/0008-5472.CAN-22-2593}, pmid = {37433041}, issn = {1538-7445}, abstract = {Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of ESCC patients to NACI. Intra-tumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing (scRNA-seq) demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ Treg cells. Mice that underwent fecal microbial transplantation (FMT) or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy.}, } @article {pmid37432606, year = {2023}, author = {Feitelson, MA and Arzumanyan, A and Medhat, A and Spector, I}, title = {Short-chain fatty acids in cancer pathogenesis.}, journal = {Cancer metastasis reviews}, volume = {}, number = {}, pages = {}, pmid = {37432606}, issn = {1573-7233}, abstract = {Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types. Dysbiosis is often characterized by diminished levels of SCFAs in the stool, and the presence of a "leaky gut," permitting the penetration of microbes and microbial derived molecules (e.g., lipopolysaccharides) through the gut wall, thereby triggering chronic inflammation. SCFAs attenuate inflammation by inhibiting the activation of nuclear factor kappa B, by decreasing the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha, by stimulating the expression of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor beta, and by promoting the differentiation of naïve T cells into T regulatory cells, which down-regulate immune responses by immunomodulation. SCFA function epigenetically by inhibiting selected histone acetyltransferases that alter the expression of multiple genes and the activity of many signaling pathways (e.g., Wnt, Hedgehog, Hippo, and Notch) that contribute to the pathogenesis of cancer. SCFAs block cancer stem cell proliferation, thereby potentially delaying or inhibiting cancer development or relapse by targeting genes and pathways that are mutated in tumors (e.g., epidermal growth factor receptor, hepatocyte growth factor, and MET) and by promoting the expression of tumor suppressors (e.g., by up-regulating PTEN and p53). When administered properly, SCFAs have many advantages compared to probiotic bacteria and fecal transplants. In carcinogenesis, SCFAs are toxic against tumor cells but not to surrounding tissue due to differences in their metabolic fate. Multiple hallmarks of cancer are also targets of SCFAs. These data suggest that SCFAs may re-establish homeostasis without overt toxicity and either delay or prevent the development of various tumor types.}, } @article {pmid37431863, year = {2023}, author = {Han, B and Lv, X and Liu, G and Li, S and Fan, J and Chen, L and Huang, Z and Lin, G and Xu, X and Huang, Z and Zhan, L and Lv, X}, title = {Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4β7-integrin therapy in humanized mice with colitis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2232143}, pmid = {37431863}, issn = {1949-0984}, mesh = {Animals ; Mice ; Humans ; *Gastrointestinal Microbiome ; Caco-2 Cells ; *Colitis/chemically induced/drug therapy ; *Inflammatory Bowel Diseases ; Bile Acids and Salts ; Integrins ; }, abstract = {The gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4β7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4β7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4β7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4β7-integrin in expe