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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 07 Apr 2025 at 01:46 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: ( "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-04-06
CmpDate: 2025-04-03

Clavijo-Salomon MA, G Trinchieri (2025)

Unlocking the power of the microbiome for successful cancer immunotherapy.

Journal for immunotherapy of cancer, 13(4):.

In recent years, evidence has shown that the gut microbiome significantly influences responses to immunotherapy. This has sparked interest in targeting it to improve therapy outcomes and predictions of response and toxicity. Research has demonstrated that dysbiosis, often resulting from antibiotic use, can diminish the effectiveness of immune checkpoint inhibitors, and this lack of efficacy could be linked to systemic inflammation. Certain bacterial species have been identified as having beneficial and harmful effects on immunotherapy in the clinic. While a clear consensus has yet to emerge on the optimal species for therapeutic use, introducing a new microbiome into immunotherapy-refractory patients may boost their chances of responding to further treatment attempts. State-of-the-art interventions targeting the microbiome-such as fecal microbiota transplantation-are being assessed clinically for their safety and potential to enhance treatment outcomes, with promising results. Additionally, the microbiome has been leveraged for its power to predict clinical outcomes using machine learning, and surprisingly, its predictive capability is comparable to that of other described multi-biomarker clinical scores. Here, we discuss developing knowledge concerning the microbiome's significance in cancer immunotherapy and outline future strategies for maximizing its potential in immuno-oncology.

RevDate: 2025-04-04

Liu J, Li F, Yang L, et al (2025)

Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM.

Frontiers in microbiology, 16:1554189.

The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.

RevDate: 2025-04-05

Wu Y, Chen X, Wu Q, et al (2025)

Research progress on fecal microbiota transplantation in tumor prevention and treatment.

Open life sciences, 20(1):20220954.

The application of fecal microbiota transplantation (FMT) as a therapeutic strategy to directly modify the makeup of the gut microbiota has made significant progress in the last few decades. The gut microbiota, a sizable microbial community present in the human gut, is essential for digestion, immunomodulation, and nutrition absorption. Alternatively, a growing body of research indicates that gut microbiota is a key contributor to cancer, and intratumoral bacteria are considered to be crucial "accomplices" in the development and metastasis of malignancies. The exceptional clinical effectiveness of FMT in treating melanoma patients has been adequately established in earlier research, which has created new avenues for the diagnosis and treatment of cancer and sparked an increasing interest in the treatment and prevention of other cancers. However, further research on the function and mechanisms of the gut microbiota is required to properly comprehend the impact and role of these organisms in tumor regulation. In this article, we present a detailed account of the influence of FMT on the entire course of cancer patients' illness and treatment, from tumor development, metastasis, and invasion, to the impact and application of treatment and prognosis, as well as address the associated mechanisms.

RevDate: 2025-04-04
CmpDate: 2025-04-03

Yarahmadi A, Najafiyan H, Yousefi MH, et al (2025)

Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.

Frontiers in cellular and infection microbiology, 15:1493915.

Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.

RevDate: 2025-04-04
CmpDate: 2025-04-03

Sommer F, Bernardes JP, Best L, et al (2025)

Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.

Microbiome, 13(1):91.

BACKGROUND: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.

RESULTS: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.

CONCLUSIONS: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.

RevDate: 2025-04-05
CmpDate: 2025-04-03

Ahn JS, Kim S, Han EJ, et al (2025)

Increasing spatial working memory in mice with Akkermansia muciniphila.

Communications biology, 8(1):546.

Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.

RevDate: 2025-04-05

Braga JD, Yang Y, Nagao T, et al (2025)

Fructooligosaccharides and Aspergillus enzymes increase brain GABA and homocarnosine by modulating microbiota in adolescent mice.

NPJ science of food, 9(1):48.

Recent research suggests that dietary prebiotics, probiotics, or healthy fecal-microbiota transplantation attenuate gut microbiota dysbiosis and ameliorate neurological disorders, in which gut-microbiota-derived γ-aminobutyric acid (GABA) has gained much attention as one of key mediators in the gut-brain axis. Although it is widely accepted that prebiotics and probiotics induce gut and brain GABA production via modulating gut microbiota, only evidence of probiotics has been solidly demonstrated while this evidence of prebiotics is scarce. Here, we demonstrated that prebiotic fructo-oligosaccharides and Aspergillus-derived enzymes elevated gut and brain GABA concentrations by modulating gut microbiota. Interestingly, we found that the prebiotic and enzymes increased a brain-specific dipeptide, homocarnosine. Gut GABA levels were found correlated with brain GABA/homocarnosine levels. Parabateroides, Akkermansia, Muribaculum, Hungatella, Marvinbryantia, Flavonifractor, and Incertae_sedis exhibited a positive correlation with gut GABA and brain GABA/homocarnosine levels, while Blautia, Unclassified_Lachnospiraceae, Colidextribacter, Acetatifactor, Roseburia, Unclassified_Oscillospiraceae, Romboutsia, and Eubacterium_coprostanoligenes exhibited a negative correlation with those levels.

RevDate: 2025-04-02

Abavisani M, Tafti P, Khoshroo N, et al (2025)

The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases.

Pathology, research and practice, 269:155931 pii:S0344-0338(25)00123-2 [Epub ahead of print].

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

RevDate: 2025-04-03
CmpDate: 2025-04-02

Li C, Cheng D, Ren H, et al (2025)

Unraveling the gut microbiota's role in PCOS: a new frontier in metabolic health.

Frontiers in endocrinology, 16:1529703.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.

RevDate: 2025-04-03
CmpDate: 2025-04-02

Chen F, Zhang H, Wei Q, et al (2025)

Disrupted gut microbiota promotes the progression of chronic kidney disease in 5/6 nephrectomy mice by Bacillus pumilus gavage.

Frontiers in cellular and infection microbiology, 15:1548767.

BACKGROUND: Our previous study identified differences in the gut microbiota between patients with chronic kidney disease (CKD) and healthy individuals. We observed that antibiotic-treated mice exhibited symptoms similar to those of patients with CKD after receiving a gut microbiota transplant from patients with CKD. Bacillus pumilus (B. pumilus), an alien microorganism to both human and mouse gut microbiota, possesses antibiotic properties that can alter the microbial community structure. Therefore, this study aimed to explore how changes in the gut microbiota structure induced by the oral gavage of B. pumilus affect the progression of CKD. We sought to identify the gut microbes and metabolic pathways associated with CKD to lay the groundwork for future clinical probiotic applications in patients with CKD.

METHODS: We constructed sham-operated and 5/6 nephrectomy mice as the sham control (SC) and CKD models, respectively. CKD models were divided into a control group (CG) and an intervention group (IG). After 16 weeks of normal feeding, the IG were treated with B. pumilus by oral gavage, while SC and CG were treated with PBS once daily, 5 days per week, for 7 weeks. Fecal samples were collected for 16s rRNA sequencing and metabolomic analysis, kidneys were harvested for histological examination, and the colon was used for RT-PCR analysis.

RESULTS: B. pumilus intervention exacerbated gut microbial homeostasis in CKD mice and increased serum creatinine and urea nitrogen levels, further aggravating kidney damage. 16s rRNA and metabolomic analysis revealed that Parvibacter and Enterorhabdus were probiotics related to kidney function, while Odoribacter was associated with kidney injury. Metabolomic analysis showed that glycerophospholipid and lysine metabolism were upregulated in CKD model mice, correlating with kidney damage.

CONCLUSION: This study shows that changes in the gut microbiota can affect the kidneys through gut metabolism, confirming that the lack of probiotics and the proliferation of harmful bacteria leading to gut microbiota dysbiosis are drivers of CKD progression. Our findings provide a basis for clinical interventions using gut microbes and offer a reference for targeted probiotic therapy.

RevDate: 2025-04-05
CmpDate: 2025-04-02

Yao N, Liu Y, Zhang ZY, et al (2025)

Excretion and clearance of Sabin-like type 3 poliovirus in a child diagnosed with severe combined immunodeficiency.

Human vaccines & immunotherapeutics, 21(1):2484882.

Children with primary immunodeficiency disorder (PID) are at higher risk of developing vaccine-associated paralytic poliomyelitis (VAPP) or vaccine-derived polioviruses (VDPV) infection when inadvertently expose to poliovirus vaccine, oral (OPV). A pilot study was initiated to describe the epidemiology of immunodeficiency-associated VDPV (iVDPV) and to estimate the risk of iVDPV shedding among individuals with PID. Children under 18 years of age newly diagnosed with PID were recruited for investigation and tested for poliovirus excretion. Children with poliovirus-positive stool samples had regular follow-up testing for poliovirus excretion and determination of clinical prognosis. A patient with severe combined immunodeficiency (SCID) with compound heterozygous mutations in the RAG1 gene was found to be excreting Sabin-like type 3 (SL3) poliovirus. Excretion stopped six weeks after hematopoietic stem-cell transplantation (HSCT). Graft versus host disease (GVHD) and poor graft function (PGF) occurred after HSCT, resulting in failure of hematopoiesis and immune system reconstitution. Given deficient innate and adaptive immunity, immune-mediated destruction of gastrointestinal (GI) tract caused by GVHD and inflammatory diarrheal illness of the girl may have contributed to her clearance of SL3 poliovirus. Intermittent surveillance of immune system parameters for iVDPV excreters receiving HSCT should be included in the PID surveillance program for further understanding poliovirus clearance mechanisms.

RevDate: 2025-04-02

Zheng Y, Chen J, Zhang Y, et al (2025)

Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.

Phytotherapy research : PTR [Epub ahead of print].

Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens, and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.

RevDate: 2025-04-01

Shi Y, Jiang M, Zhu W, et al (2025)

Cyclosporine combined with dexamethasone regulates hepatic Abca1 and PPARα expression and lipid metabolism via butyrate derived from the gut microbiota.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 186:118017 pii:S0753-3322(25)00211-2 [Epub ahead of print].

Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.

RevDate: 2025-04-01

Ishikawa D, Watanabe H, Nomura K, et al (2025)

Patient-donor similarity and donor-derived species contribute to the outcome of faecal microbiota transplantation for ulcerative colitis.

Journal of Crohn's & colitis pii:8102791 [Epub ahead of print].

BACKGROUND AND AIMS: Clinical applications of faecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonisation of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.

METHODS: Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 faecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one patient-to-one donor strategy.

RESULTS: Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (p = 0.027), immunosuppressants (p = 0.049), and biologics (p = 0.029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; p = 0.03, LTR; p = 0.05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (p < 0.05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (p < 0.05).

CONCLUSIONS: This study provides important insights for developing patient-tailored FMT-based therapies for UC.

RevDate: 2025-04-01

Xiang M, Wu S, Liu M, et al (2025)

Iota-carrageenan oligosaccharide ameliorates DSS-induced colitis in mice by mediating gut microbiota dysbiosis and modulating SCFAs-PI3K-AKT pathway.

Inflammopharmacology [Epub ahead of print].

Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia. They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1, BDKRB1, LCN2, and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses.

RevDate: 2025-04-01
CmpDate: 2025-04-01

Huang M, Ji Q, Huang H, et al (2025)

Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.

Gut microbes, 17(1):2486519.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.

RevDate: 2025-04-01

Zhang Z, Zhu T, Li Y, et al (2025)

Butyrate Regulates Intestinal DNA Virome and Lipopolysaccharide Levels to Prevent High-Fat Diet-Related Liver Damage in Rats.

Journal of agricultural and food chemistry [Epub ahead of print].

As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.

RevDate: 2025-04-02

Halvorsen N, Hassan C, Correale L, et al (2025)

Benefits, burden, and harms of computer aided polyp detection with artificial intelligence in colorectal cancer screening: microsimulation modelling study.

BMJ medicine, 4(1):e001446.

OBJECTIVE: To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.

DESIGN: Microsimulation modelling study.

SETTING: Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.

POPULATION: Four cohorts of 100 000 European individuals aged 60-69 years.

INTERVENTION: The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.

MAIN OUTCOME MEASURES: Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10 years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

RESULTS: For 100 000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.

CONCLUSION: With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.

RevDate: 2025-04-02
CmpDate: 2025-04-01

Ding W, Cheng Y, Liu X, et al (2025)

Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.

Frontiers in immunology, 16:1563450.

Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight against AMR. In contrast, gut dysbiosis disrupts this defense, thereby facilitating the persistence, colonization, and dissemination of resistant pathogens. This review will explore how gut microbiota influence drug-resistant bacterial infections, its involvement in various types of AMR-related infections, and the potential for novel microbiota-targeted therapies, such as fecal microbiota transplantation, prebiotics, probiotics, phage therapy. Elucidating the interactions between gut microbiota and AMR pathogens will provide critical insights for developing novel therapeutic strategies to prevent and treat AMR infections. While previous reviews have focused on the general impact of the microbiota on human health, this review will specifically look at the latest research on the interactions between the gut microbiota and the evolution and spread of AMR, highlighting potential therapeutic strategies.

RevDate: 2025-04-01

Wang L, Shao L, Gao YC, et al (2025)

Panax notoginseng Saponins Alleviate Inflammatory Bowel Disease via Alteration of Gut Microbiota-Bile Acid Metabolism.

The American journal of Chinese medicine [Epub ahead of print].

Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.

RevDate: 2025-04-01

Jia L, Ke Y, Zhao S, et al (2025)

Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer's disease.

Molecular psychiatry [Epub ahead of print].

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a decade-long preclinical pathological period that can be divided into several stages. Emerging evidence has revealed that the microbiota-gut-brain axis plays an important role in AD pathology. However, the role of gut microbiota in different AD stages has not been well characterized. In this study, we performed fecal shotgun metagenomic analysis on a Chinese cohort with 476 participants across five stages of AD pathology to characterize stage-specific alterations in gut microbiota and evaluate their diagnostic potential. We discovered extensive gut dysbiosis that is associated with neuroinflammation and neurotransmitter dysregulation, with over 10% of microbial species and gene families showing significant alterations during AD progression. Furthermore, we demonstrated that microbial gene families exhibited strong diagnostic capabilities, evidenced by an average AUC of 0.80 in cross-validation and 0.75 in independent external validation. In the optimal model, the most discriminant gene families are primarily involved in the metabolism of carbohydrates, amino acids, energy, glycan and vitamins. We found that stage-specific microbial gene families in AD pathology could be validated by an in vitro gut simulator and were associated with specific genera. We also observed that the gut microbiota could affect the progression of cognitive decline in 5xFAD mice through fecal microbiota transplantation, which could be used for early intervention of AD. Our multi-stage large cohort metagenomic analysis demonstrates that alterations in gut microbiota occur from the very early stages of AD pathology, offering important etiological and diagnostic insights.

RevDate: 2025-03-31

Cintosun A, Jamal I, Samnani S, et al (2025)

Gastroenterology/Hepatology: What You May Have Missed in 2024.

Annals of internal medicine [Epub ahead of print].

This article highlights selected major advances in gastroenterology and hepatology from 2024 that are relevant for internal medicine specialists. In colorectal cancer (CRC) screening, new developments include a head-to-head comparison of different fecal immunochemical tests and a new blood-based DNA screening test, benefits and harms of artificial intelligence-assisted colonoscopy, and adenoma detection rate improvement and risk for cancer. Treatment options for metabolic dysfunction-associated steatotic liver disease now include resmetirom, a recently approved drug for treatment of patients with moderate-to-severe fibrosis, and liver transplantation may now be an option in patients with unresectable colorectal liver metastases. Also featured are new data on the efficacy of indomethacin and pancreatic stent placement for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography and news on the efficacy and safety of zastaprazan, a new potassium-competitive acid blocker for reflux esophagitis. Finally, a recent randomized trial is highlighted that has dispelled concerns about potential harms of proton-pump inhibitors for stress ulcer prophylaxis in patients receiving invasive mechanical ventilation.

RevDate: 2025-03-31
CmpDate: 2025-03-31

Sigtryggsson AT, Helgason KO, Bjarnason A, et al (2025)

[Clostridioides difficile infections at Landspítali University Hospital 2017-2022].

Laeknabladid, 111(4):158-165.

OBJECTIVE: To investigate the epidemiology, severity, treatment, and prognosis of patients with C. difficile infections (CDI) diagnosed at Landspítali University Hospital from 2017-2022.

MATERIALS AND METHODS: The study population consisted of adult patients at Landspítali with double-positive (PCR + ELISA) diagnostic tests. If the same patient had two or more positive samples within a 28-day period, they were considered to reflect the same infection, and the latter samples were excluded.

RESULTS: Overall, 358 CDI were identified in 301 patients. The majority of cases were diagnosed in women (59.5%). The incidence of healthcare-associated CDI was 3.23 infections/10.000 in-hospital days (range 2.65 - 3.26). Incidence of community-associated CDI was 0.57 infections/10.000 inhabitants of the Reykjavik metropolitan area. Incidence was positively correlated with increasing age and remained similar throughout the study period. The recurrence rate during the study period was 15.3% with a mean follow-up period of 1.6 person-years. At least 85.5% of patients had taken antibiotics within a month before diagnosis, most commonly from the penicillin class (57.8%), followed by cephalosporins (51.5%). More than half (54.7%) of patients had taken proton pump inhibitors preceding diagnosis. Metronidazole was the most common initial treatment (63.0%). Of these, 29.4% of cases required further treatment within 28 days of treatment start. Fecal microbiota transplantation was performed in 13 cases. The 30-day all-cause mortality rate was 7.3%.

CONCLUSIONS: The incidence of CDI at Landspítali has remained stable and comparable to what has been reported in Europe during the same period. Most patients had one or more risk factors present. Most received antibiotics as treatment, most commonly metronidazole. The results of this study indicate that incidence and clinical presentation of CDI in Iceland are stable, whilst novel treatment options look promising.

RevDate: 2025-03-31

Zhong XS, Lopez KM, Krishnachaitanya SS, et al (2025)

Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.

bioRxiv : the preprint server for biology pii:2025.03.13.643179.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.

METHODS: We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 [-/-] spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.

RESULTS: Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and β-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1 , Map3k6 , Pck1 , Cfd), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 [-/-] colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes (Lbp and Cdkn1a in Il10 [-/-] mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 [-/-] mice. Notably, Il10 [-/-] mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.

CONCLUSIONS: Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.

RevDate: 2025-04-02

Dai W, Chen X, Zhou H, et al (2025)

Microbiota modulation for infectious complications following allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies.

Frontiers in pediatrics, 13:1509612.

The intervention of microbiota modulation in the treatment of infection complications after allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies has shown potential benefits. Through the use of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), these interventions modulate the gut microbiota and enhance immune function to prevent and treat infections. They have been shown to reduce the incidence of diarrhea and intestinal infections, mitigate the issue of antibiotic resistance, and promote the recovery of gut microbiota. Future research is needed to further assess the safety and efficacy of these interventions and to establish standardized treatment protocols.

RevDate: 2025-04-02

Tucker EC, Angelica B, Mathias RM, et al (2025)

Outcomes of Fecal Microbiota Transplantation for Clostridioides difficile Infection in South Australia.

Open forum infectious diseases, 12(4):ofaf149.

BACKGROUND: Fecal microbiota transplantation (FMT) sourced from a bank of prescreened anaerobically processed frozen donor stool has been available in South Australia since 2013. This study aimed to evaluate the real-world clinical and safety outcomes of FMT for recurrent, refractory, and/or severe or fulminant Clostridioides difficile infection (CDI) facilitated via this centralized facility.

METHODS: Donor screening test data were prospectively collected on all donors who passed prescreening evaluations between April 2013 and August 2023. The South Australian FMT for CDI database prospectively recorded outcomes for consecutive patients who underwent FMT for CDI from August 2013 to May 2023 in South Australia.

RESULTS: An overall 98 potential donors passed prescreening assessments and underwent laboratory screening tests: 32 (33%) had tests that failed, 5 (5%) had incomplete screening, and 61 (62%) passed. Detection of an extended-spectrum β-lactamase-producing organism (9/65, 14%) was the common reason for ineligibility following completion of screening tests. In total 220 cases of CDI were recorded, and follow-up data were available in 216. Primary cure occurred in 84% of cases (182/216): 88% (132/150) for recurrent CDI, 76% (50/66) for refractory CDI, 85% (51/60) for severe disease, and 65% (17/26) for fulminant disease. Repeat FMT was delivered in 23 of 34 cases (68%), with secondary cure in 74% (17/23 cases). Serious adverse events were observed in 6 patients overall (3%). No deaths were directly attributable to FMT.

CONCLUSIONS: FMT was safe and efficacious for management of recurrent and refractory CDI over a 10-year period in a real-world prospective Australian cohort. Further studies to optimize the use of FMT for severe and fulminant CDI are warranted.

RevDate: 2025-04-02

Cao Z, Gao T, Bajinka O, et al (2025)

Fecal microbiota transplantation-current perspective on human health.

Frontiers in medicine, 12:1523870.

Recently, microbiome medicine has attracted the attention of researchers. While this rapidly growing medical approach for various diseases and disorders is changing the paradigm, it is imperative to weigh both its benefits and the associated risk factors. For instance, manipulation of the gut microbiota (GM) has positive effects on metabolic and neurodegenerative diseases. Notably, fecal microbiota transplantation (FMT), a complex method, has shown promise; however, many doubt its feasibility without adverse effects on human health. Given the number of human clinical trials investigating FMT for the treatment of various disorders, this review summarizes recent findings on its impact on human health. This review summarizes the metabolic responses associated with FMT and their reversal effects on gastrointestinal infections, behavioral changes, and immune responses. Additionally, this review discusses the role of FMT in antimicrobial resistance and its co-supplementation effects on human health, safety, potential risks, limitations, prospects, and recommendations. Although this review does not cover all the studies in the database, the searched terms for FMT and human health in clinical trials are sufficient to provide a summary of the current perspective.

RevDate: 2025-03-30

Bretthauer M, M Kalager (2025)

First head-to-head trial of colonoscopy versus faecal testing for colorectal cancer screening.

Lancet (London, England) pii:S0140-6736(25)00288-0 [Epub ahead of print].

RevDate: 2025-03-29

Han Y, Zhang Y, Chen J, et al (2025)

Iron overload exacerbates metabolic dysfunction-associated steatohepatitis via the microbiota-gut-liver axis through lipopolysaccharide-mediated Akr1b8 activation.

Free radical biology & medicine pii:S0891-5849(25)00189-3 [Epub ahead of print].

Iron homeostatic is closely linked to the development of metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanisms remain poorly understood. HFE knockout (KO) mice were used to generate mild iron-overload models. MASH was induced by feeding mice a methionine- and choline-deficient (MCD) diet for 4 weeks. Iron overload significantly exacerbated the pathologies of MCD-induced MASH, including liver injury, hepatic lipid accumulation, inflammation, and fibrosis. Additionally, iron overload reshaped the composition of gut microbiota, and fecal microbiota transplantation assay proved that gut microbiota from iron-overload mice contributed to hepatic lipid accumulation in control mice. Furthermore, iron overload-induced dysbacteriosis altered the metabolite profiles, reducing short-chain fatty acid levels and increasing lipopolysaccharide (LPS) levels. Notably, elevated LPS levels upregulated the expression of aldo-keto reductase family 1 member B8 (Akr1b8), which accelerated lipid accumulation and inflammation in hepatocytes. Above results indicated that iron overload promoted MASH progression through the microbiota-gut-liver axis, mediated by LPS-induced activation of Akr1b8. These findings highlight the critical role of iron homeostasis and gut microbiota in MASH pathogenesis.

RevDate: 2025-03-29

Rahimi A, Baghernejadan Z, Hazrati A, et al (2025)

Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 186:118014 pii:S0753-3322(25)00208-2 [Epub ahead of print].

Colorectal cancer (CRC) is still one of the leading causes of cancer deaths worldwide. Even though there has been progress in cancer immunotherapy, the results of applying immune checkpoint inhibitors (ICIs) have been unsatisfactory, especially in microsatellite stable (MSS) CRC. Single-agent ICIs that target programmed cell death-1 (PD-1)/ PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene (LAG)-3 have emerged as having specific benefits. However, many primary and secondary resistance mechanisms are available in the tumor microenvironment (TME) that prevent it from happening. Combination strategies, such as the use of anti-PD-1 and anti-CTLA-4, can be effective in overcoming these resistance pathways, but toxicities remain a significant concern. Moreover, ICIs have been integrated with various treatment modalities, including chemotherapy, radiotherapy, antibiotics, virotherapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and heat shock protein 90 (HSP90) inhibitors. The outcomes observed in both preclinical and clinical settings have been encouraging. Interestingly, manipulating gut microbiota via fecal microbiota transplantation (FMT) has been identified as a new strategy to increase the efficacy of immunotherapy in CRC patients. Therefore, integrating ICIs with other treatment approaches holds promise in enhancing the prognosis of CRC patients. This review focuses on the unmet need for new biomarkers to select patients for combination therapies and the ongoing work to overcome resistance and immune checkpoint blockade.

RevDate: 2025-03-31
CmpDate: 2025-03-29

Karataş M, Bloemen M, Cuypers L, et al (2025)

14 years of rotavirus A surveillance: unusual dominance of equine-like G3P[8] genotype with DS-1-like genotype constellation after the pandemic, Belgium, 2009 to 2023.

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 30(12):.

IntroductionDespite vaccine availability, rotavirus persists as a leading cause of gastroenteritis in children younger than 5 years.AimWe aimed to evaluate temporal changes in rotavirus epidemiology in Belgium between 2009 and 2023, including the period of the COVID-19 pandemic.MethodsWe collected 8,024 rotavirus-positive stool samples throughout Belgium. For 6,352 samples, we determined the G and/or P genotypes through sequencing of the genes encoding the outer capsid proteins VP7 and VP4.ResultsBefore the COVID-19pandemic, we received on average 622 samples per rotavirus epidemiological year, which decreased to 114 and 111 samples during the two pandemic rotavirus epidemiological years, followed by a peak of 1,048 samples in the first post-pandemic year. Notably, the proportion of cases in the age group 2-5-years increased from 20.3% before to 33% after the pandemic (p < 0.001). Over the 14-year study period, the most common genotypes were G2P[4], G3P[8] and G9P[8]. Post-pandemic data show an unusually strong dominance of the equine-like G3P[8] genotype which carried a DS-1-like genotype constellation in the period 2021 to 2023. Additionally, vaccinated individuals were significantly overrepresented among patients infected with the equine-like VP7 carrying G3P[8] rotavirus compared with other genotypes, including typical human VP7 G3P[8].ConclusionDespite the presence of typical yearly genotype fluctuations, several epidemiological changes were associated with the COVID-19 pandemic, including the unusual dominance of an emerging rotavirus strain against which current vaccines may be less effective. It is essential to closely monitor this strain to determine if the phenomenon is temporary.

RevDate: 2025-03-28

Lin SM, Le PH, Chen CL, et al (2025)

Fecal microbiota transplantation to decolonize vancomycin-resistant Enterococcus: A pilot study to evaluate safety and clinical outcome.

Journal of global antimicrobial resistance pii:S2213-7165(25)00069-4 [Epub ahead of print].

OBJECTIVES: Fecal microbiota transplantation (FMT) has shown promise as a treatment for recurrent or refractory Clostridioides difficile infections. This study aimed to evaluate the decolonization effects of FMT on vancomycin-resistant Enterococcus (VRE).

METHODS: This feasibility trial prospectively recruited patients with more than three recurrent VRE infections. FMT was performed by infusing fecal microbiota solutions from healthy, unrelated donors into the participants' guts via colonoscopy. Fecal microbiota profiles before and after FMT were analyzed.

RESULTS: Three of the six patients (50%) experienced VRE decolonization after FMT, lasting over six months. Baseline analysis revealed that patients who achieved decolonization had greater microbial diversity compared to those with persistent VRE colonization. Throughout the study, there were no adverse events observed in the patients after FMT. Elevated alpha diversity persisted in responders, while non-responders showed no significant changes. In responders, the abundance of genera within the phylum Firmicutes (Bacillota), including Anaerostipes, Blautia, Faecalibacterium, and Ruminococcus, and the genus Collinsella within the phylum Actinobacteriota increased steadily through 180 days post-FMT.

CONCLUSIONS: FMT may leverage bacterial strain competition to facilitate decolonization of drug-resistant organisms, with successful VRE decolonization potentially linked to increased abundance of phyla Firmicutes and Actinobacteriota over 6 months.

RevDate: 2025-03-28

Martin D, Bonneau M, Orfila L, et al (2025)

Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice.

Cell reports pii:S2211-1247(25)00219-0 [Epub ahead of print].

Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.

RevDate: 2025-03-30
CmpDate: 2025-03-28

Gabarre P, Palacios R, Perez K, et al (2025)

Immunosuppressive drugs and diet interact to modify the gut microbiota and cardiovascular risk factors, and to trigger diabetes.

PloS one, 20(3):e0320438.

BACKGROUND: Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.

METHODS: 8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.

RESULTS: The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.

CONCLUSION: The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.

RevDate: 2025-03-29

Cai X, Cho JY, Chen L, et al (2025)

Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types.

iScience, 28(4):112162.

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore, luxS, manA, fliC, and trpB exhibited consistent changes between R and NR across 12 datasets. Follow-up microbiota transplant experiments showed that inter-species signaling by different QS autoinducer-2 (AI-2) molecules (synthesized by luxS) can act on overall community function to promote the colonization of Akkermansia muciniphila, which is associated with superior ICI responses. Together, our data highlight the role of gut microbiota function in modulating the microbiome and antitumor immunity.

RevDate: 2025-03-30

Wang K, Suo Y, Shen D, et al (2025)

Improvement in Heat Stress-Induced Damage to Sperm Quality Following Fecal Microbiota Transplantation from L-Arginine-Treated Mice.

Animals : an open access journal from MDPI, 15(6):.

Heat stress has become a significant concern in animal husbandry, as it adversely affects reproductive performance, particularly sperm quality, through mechanisms that are not fully understood. This study aimed to investigate the protective effects of L-arginine against heat stress-induced sperm damage and explore its potential mechanisms through the modulation of the intestinal microbiota. This study consisted of two experiments. First, in a heat-stressed mouse model, L-arginine was administered to evaluate its effects on the reproductive health of heat-stressed mice. In the second experiment, by transplanting L-arginine-induced changes in the gut microbiota into heat-stressed mice, the protective effects of the microbiota on the sperm of heat-stressed mice were assessed. The findings revealed a significant amelioration of decreased sperm quality and testicular injury induced by heat stress. Post heat stress, mice supplemented with L-arginine presented an increase in seminal vesicle gland weight and index, partial alleviation of testicular tissue morphology, and a substantial increase in testosterone concentration (p < 0.05). Additionally, L-arginine upregulated the expression of testosterone synthesis genes and the mRNA levels of sperm generation-related genes, including 3β-HSD, Stra8, WT1, and Gdnf (p < 0.05). Concurrently, L-arginine-induced microbial communities mitigated heat stress-induced decreases in sperm quality and testicular injury, coupled with increases in the mRNA expression levels of Cyp17a1, 17β-HSD, Plzf, and Gdnf (p < 0.05). Furthermore, there was a reduction in the expression of proinflammatory factors, namely, NFκB, MyD88, TNF-α, and TGF-β3 (p < 0.05). In conclusion, L-arginine may influence the ratio of beneficial bacteria to harmful bacteria in the intestinal microbiota, thereby reducing inflammation caused by heat stress, maintaining intestinal health, and influencing the microenvironment for spermatogenesis.

RevDate: 2025-03-30

Sivakumar N, Krishnamoorthy A, Ryali H, et al (2025)

Gut Microbial Targets in Inflammatory Bowel Disease: Current Position and Future Developments.

Biomedicines, 13(3):.

Inflammatory bowel disease (IBD) is a debilitating condition in which surgery is often seen as a last resort. However, this is associated with morbidity and, in some cases, mortality. There are emerging therapies that seek to better modulate the immune response of hosts with IBD. Aims: The main aim of this study is to focus on novel therapies and techniques studied in the last year that are non-surgical treatments of IBD. Methods: We looked at all the research between March 2024 and February 2025 detailing treatment in IBD and focused on the gut microbiome and gene therapy. Results: Novel therapies are gaining traction in safety and popularity. The results from some animal studies show promise and, with FDA approval, some probiotic therapies show optimistic research potential for future human trials. Conclusions: The research into the diagnostics and novel therapies available on the horizon for humans is very promising. Animal studies have shown potentially transferrable and safe therapies that can target specific sites of inflammation. Modulating the inflammatory response is a powerful therapy with what is shown to be a reasonably safe profile to build further research on.

RevDate: 2025-03-30

Zhang B, Mohd Sahardi NFN, Di W, et al (2025)

The Gut-Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer-A Narrative Review.

Cancers, 17(6):.

Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut-endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes.

RevDate: 2025-03-30

Kenneth MJ, Wu CC, Fang CY, et al (2025)

Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.

Antibiotics (Basel, Switzerland), 14(3):.

With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.

RevDate: 2025-03-27
CmpDate: 2025-03-27

Foroutan F, Vandvik PO, Helsingen LM, et al (2025)

Computer aided detection and diagnosis of polyps in adult patients undergoing colonoscopy: a living clinical practice guideline.

BMJ (Clinical research ed.), 388:e082656.

CLINICAL QUESTION: In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)?

CONTEXT AND CURRENT PRACTICE: Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient.

EVIDENCE: Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30 000 participants and a companion microsimulation study simulating 10 year follow-up for 100 000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance.

RECOMMENDATION: For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation).

An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation UNDERSTANDING THE RECOMMENDATION: The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens-including more frequent surveillance colonoscopies-are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use.The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate.

UPDATES: This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ.

RevDate: 2025-03-27

Shawcross DL, VC Patel (2025)

FMT for Hepatic Encephalopathy? The THEMATIC Trial aims to make is a 'no brainer'.

RevDate: 2025-03-27

Ye X, An X, Zhang T, et al (2025)

CGA protects against experimental colitis by modulating host purine metabolism through the gut microbiota.

International immunopharmacology, 153:114547 pii:S1567-5769(25)00537-5 [Epub ahead of print].

OBJECTIVE: Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.

METHODS: A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.

RESULTS: CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.

CONCLUSION: CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.

RevDate: 2025-03-28

Zhou M, Niu B, Ma J, et al (2025)

Intervention and research progress of gut microbiota-immune-nervous system in autism spectrum disorders among students.

Frontiers in microbiology, 16:1535455.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive and stereotyped behaviors, restricted interests, and sensory abnormalities. Its etiology is influenced by both genetic and environmental factors, with no definitive cause identified and no specific pharmacological treatments available, posing a significant burden on patients' families and society. In recent years, research has discovered that gut microbiota dysbiosis plays a crucial role in the pathogenesis of ASD. The gut microbiota can influence brain function and behavior through the gut-brain axis via the nervous system, immune system, and metabolic pathways. On the one hand, specific gut microbes such as Clostridium and Prevotella species are found to be abnormal in ASD patients, and their metabolic products, like short-chain fatty acids, serotonin, and GABA, are also involved in the pathological process of ASD. On the other hand, ASD patients exhibit immune system dysfunction, with gut immune cells and related cytokines affecting neural activities in the brain. Currently, intervention methods targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, have shown some potential in improving ASD symptoms. However, more studies are needed to explore their long-term effects and optimal treatment protocols. This paper reviews the mechanisms and interrelationships among gut microbiota, immune system, and nervous system in ASD and discusses the challenges and future directions of existing research, aiming to provide new insights for the prevention and treatment of ASD.

RevDate: 2025-03-27

Zhang F, Kamm MA, Wu X, et al (2025)

Preferred Reporting Items for Microbiotherapy (PRIM) Guidelines Across Medical Disciplines: An International Delphi Consensus.

Journal of gastroenterology and hepatology [Epub ahead of print].

Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.

RevDate: 2025-03-29

Niu Q, Yang K, Zhou Z, et al (2025)

Intergenerational Transmission of Gut Microbiome from Infected and Non-Infected Salmonella pullorum Hens.

Microorganisms, 13(3):.

Pullorum disease (PD) is one of the common infectious diseases in the poultry industry in the world. Our previous study showed that gut bacterial structure has a significant difference between positive and negative hens. However, the gut bacterial basis of intergenerational transmission of PD continues to elude a scientific explanation. The present study carried out fecal microbiota transplantation (FMT) in chicks of a negative group, then fecal samples of the chicks in the control team (CT), Salmonella pullorum (S. pullorum)-negative transplantation team (PN) and S. pullorum-positive transplantation team (PP) were separately collected to be analyzed for microbial structure and prediction functions. Microbial diversity results revealed that there was a large difference in the gut microbiota of these three groups. Prevotella and Parasutterella with higher abundance in PN (p < 0.05) were transplanted from gut bacteria of S. pullorum-negative hens. Furthermore, the differences of the most major microbial functions (top 100) were similar in hens and chicks, including a pentose phosphate pathway and oxidative phosphorylation. The data provided a reference for exploring the intergenerational transmission and genetic mechanisms of gut microbiota associated with S. pullorum in poultry, as well as a theoretical basis for improving intestinal health through the rational regulation of microbiota-host interactions.

RevDate: 2025-03-29

Shaheen M, McDougall C, Chan L, et al (2025)

Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection.

Microorganisms, 13(3):.

Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.

RevDate: 2025-03-29

Kume M, Din J, DF Zegarra-Ruiz (2025)

Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models.

Microorganisms, 13(3):.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.

RevDate: 2025-03-29
CmpDate: 2025-03-27

Ye Y, Abulizi A, Zhang Y, et al (2025)

Ganoderic Acid Ameliorates Ulcerative Colitis by Improving Intestinal Barrier Function via Gut Microbiota Modulation.

International journal of molecular sciences, 26(6):.

Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.

RevDate: 2025-03-29
CmpDate: 2025-03-27

Wang Y, Chen Y, Xiao Z, et al (2025)

Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model.

Renal failure, 47(1):2480749.

BACKGROUND: Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear.

METHODS: C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration via gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred in vivo. Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed.

RESULTS: FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection.

CONCLUSIONS: FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.

RevDate: 2025-03-28
CmpDate: 2025-03-27

Wu Y, Cheng R, Lin H, et al (2025)

Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.

BMC medicine, 23(1):183.

Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.

RevDate: 2025-03-26

Liang T, Jiang T, Liang Z, et al (2025)

Gut microbiota-driven BCAA biosynthesis via Staphylococcus aureus -expressed acetolactate synthase impairs glycemic control in type 2 diabetes in South China.

Microbiological research, 296:128145 pii:S0944-5013(25)00101-6 [Epub ahead of print].

An increase in branched-chain amino acid (BCAA) levels can result in insulin resistance at different stages of type 2 diabetes (T2D), however, the causes of this increase are unclear. We performed metagenomics and metabolomics profiling in patients with prediabetes (PDM), newly diagnosed diabetes (NDDM), and post-medication type 2 diabetes (P2DM) to investigate whether altered gut microbes and metabolites could explain the specific clinical characteristics of different disease stages of T2D. Here we identify acetolactate synthase (ALS) a BCAA biosynthesis enzyme in Staphylococcus aureus as a cause of T2D insulin resistance. Compared with healthy peoples, patients with PDM, NDDM, and P2DM groups, especially in P2DM group, have increased faecal numbers of S. aureus. We also demonstrated that insulin administration may be a risk factor for S. aureus infection in T2D. The presence of ALS-positive S. aureus correlated with the levels of BCAAs and was associated with an increased fasting blood glucose (FBG) and insulin resistance. Humanized microbiota transplantation experiment indicated that ALS contributes to disordered insulin resistance mediated by S. aureus. We also found that S. aureus phage can reduced the FBG levels and insulin resistance in db/db mice. The ALS-positive S. aureus are associated with insulin resistance in T2D, opening a new therapeutic avenue for the prevention or treatment of diabetes.

RevDate: 2025-03-28

Mougiou D, Gioula G, Skoura L, et al (2025)

Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome.

Journal of personalized medicine, 15(3):.

Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection's symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI.

RevDate: 2025-03-28

Zalila-Kolsi I, Dhieb D, Osman HA, et al (2025)

The Gut Microbiota and Colorectal Cancer: Understanding the Link and Exploring Therapeutic Interventions.

Biology, 14(3):.

CRC remains a significant public health challenge due to its high prevalence and mortality rates. Emerging evidence highlights the critical role of the gut microbiota in both the pathogenesis of CRC and the efficacy of treatment strategies, including chemotherapy and immunotherapy. Dysbiosis, characterized by imbalances in microbial communities, has been implicated in CRC progression and therapeutic outcomes. This review examines the intricate relationship between gut microbiota composition and CRC, emphasizing the potential for microbial profiles to serve as biomarkers for early detection and prognosis. Various interventions, such as prebiotics, probiotics, postbiotics, fecal microbiota transplantation, and dietary modifications, aim to restore microbiota balance and shift dysbiosis toward eubiosis, thereby improving health outcomes. Additionally, the integration of microbial profiling into clinical practice could enhance diagnostic capabilities and personalize treatment strategies, advancing the field of oncology. The study of intratumoral microbiota offers new diagnostic and prognostic tools that, combined with artificial intelligence algorithms, could predict treatment responses and assess the risk of adverse effects. Given the growing understanding of the gut microbiome-cancer axis, developing microbiota-oriented strategies for CRC prevention and treatment holds promise for improving patient care and clinical outcomes.

RevDate: 2025-03-26

Flores-Treviño S, Bocanegra-Ibarias P, Salas-Treviño D, et al (2025)

Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.

Expert opinion on biological therapy [Epub ahead of print].

INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.

AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridiodes difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.

EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.

RevDate: 2025-03-26
CmpDate: 2025-03-26

Gao Q, Bai M, Qi T, et al (2025)

Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections.

International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, 95(1):26126.

BACKGROUND: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD and GM play significant roles in immune regulation and in maintaining intestinal barrier function.

METHODS: This prospective case-control study included 48 consecutive pediatric patients who underwent HSCT, as well as 20 healthy children from the community. Plasma samples were collected pre- and post-HSCT, together with post-HSCT fecal samples. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured using chemiluminescence and enzyme linked immunosorbent assay, respectively. GM was analyzed by 16S rDNA next generation sequencing.

RESULTS: The incidence of BSI in pediatric HSCT recipients was 33.3% (16/48). No significant differences in serum 25(OH)D or 1,25(OH)2D3 levels were observed between the BSI and non-BSI groups either before or after transplantation, or with the healthy control group. The α-diversity of GM in BSI and non-BSI patients was significantly lower than in healthy subjects. Proteobacteria were significantly more abundant in BSI patients than in non-BSI patients (p = 0.0434) or healthy controls (p = 0.0193). Pediatric HSCT patients showed significantly higher levels of Staphylococcus (p < 0.001), Pseudomonas (p < 0.001), Enterococcus (p < 0.001), Clostridium innocuum (p = 0.0175) and Enterobacter (p = 0.0394) compared to the controls, whereas the levels of Firmicutes (p = 0.009), Actinobacteria (p < 0.001), Bifidobacterium (p < 0.001) and Faecalibacterium (p < 0.001) were significantly lower. β-diversity analysis revealed significant population differences between the three groups.

CONCLUSIONS: These results indicate there is no practical value in monitoring VD in HSCT patients. During HSCT and BSI, the GM experiences a loss of probiotics and an increase in potential pathogens.

RevDate: 2025-03-26
CmpDate: 2025-03-26

Jing Y, Wang Q, Bai F, et al (2025)

Age-related alterations in gut homeostasis are microbiota dependent.

NPJ biofilms and microbiomes, 11(1):51.

Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.

RevDate: 2025-03-26
CmpDate: 2025-03-26

Tillett BJ, Dwiyanto J, Secombe KR, et al (2025)

SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome.

Nature communications, 16(1):2893.

Type 1 diabetes (T1D) is linked to an altered gut microbiota characterized by reduced short-chain fatty acid (SCFA) production. Oral delivery of a SCFA-yielding biotherapy in adults with T1D was followed by increased SCFAs, altered gut microbiota and immunoregulation, as well as delaying diabetes in preclinical models. Here, we show that SCFA-biotherapy in humans is accompanied by remodeling of the gut proteome and mucosal immune homeostasis. Metabolomics showed arginine, glutamate, nucleotide and tryptophan metabolism were enriched following the SCFA-biotherapy, and found metabolites that correlated with glycemic control. Fecal microbiota transfer demonstrated that the microbiota of SCFA-responders delayed diabetes progression in humanized gnotobiotic mice. The protected mice increased similar metabolite pathways to the humans including producing aryl-hydrocarbon receptor ligands and reducing inflammatory mucosal immunity and increasing IgA production in the gut. These data demonstrate that a potent SCFA immunomodulator promotes multiple beneficial pathways and supports targeting the microbiota as an approach against T1D. Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12618001391268.

RevDate: 2025-03-25

Duan JQ, Sun YF, Wang X, et al (2025)

Shaoyao-Gancao decoction improves dyslipidemia in rats with polycystic ovary syndrome by reshaping the gut microbiota and regulating the bile acid/FXR pathway.

Journal of Asian natural products research [Epub ahead of print].

This study aims to investigate the potential mechanism of Shaoyao-Gancao Decoction (SGD) in treating polycystic ovary syndrome (PCOS). Our results suggested that SGD effectively regulated estrous cycles, reduced body weight and serum lipid levels in PCOS rats. Additionally, SGD administration significantly remodeled the structure of gut microbiota, especially the BA-related bacteria. The mRNA expressions of BAs metabolism pathway-related genes were significantly changed by SGD treatment. Furthermore, transplantation of fecal microbiota from SGD rats verified these results. In conclusion, SGD could ameliorate dyslipidemia in PCOS rats by remodeling the structure of the gut microbiome and regulating the bile acid/FXR pathway.

RevDate: 2025-03-25

Kellingray L, Savva GM, Garcia-Gutierrez E, et al (2025)

Temporal dynamics of SARS-CoV-2 shedding in feces and saliva: a longitudinal study in Norfolk, United Kingdom during the 2021-2022 COVID-19 waves.

Microbiology spectrum [Epub ahead of print].

UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally described as a respiratory illness; however, it is now known that the infection can spread to the gastrointestinal tract, leading to shedding in feces potentially being a source of infection through wastewater. We aimed to assess the prevalence and persistence of SARS-CoV-2 in fecal and saliva samples for up to 7 weeks post-detection in a cohort of 98 participants from Norfolk, United Kingdom using RT-qPCR. Secondary goals included sequencing the viral isolates present in fecal samples and comparing the genetic sequence with isolates in the saliva of the same participant. Furthermore, we sought to identify factors associated with the presence of detectable virus in feces or saliva after a positive SARS-CoV-2 test. Saliva remained SARS-CoV-2-positive for longer periods compared to fecal samples, with all positive fecal samples occurring within 4 weeks of the initial positive test. Detectable virus in fecal samples was positively associated with the number of symptoms experienced by the individuals. Based on the genome sequencing and taxonomic classification of the virus, one donor had a distinct strain in feces compared to saliva on the same collection date, which suggests that different isolates could dominate different tissues. Our results underscore the importance of considering multiple biological samples, such as feces, in the detection and characterization of SARS-CoV-2, particularly in clinical procedures involving patient fecal material transplant. Such insights could contribute to enhancing the safety protocols surrounding the handling of patient samples and aid in devising effective strategies for mitigating the spread of coronavirus disease.

IMPORTANCE: This study provides critical insights into the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in fecal and saliva samples, demonstrating that while viral RNA is detectable shortly after diagnosis, its prevalence declines rapidly over the course of infection. Detection was more common among individuals with more concurrent symptoms, emphasizing the potential influence of symptom burden on viral persistence. By analyzing a United Kingdom-based cohort, this study fills a significant gap in the literature, which has largely focused on Asian and North American populations, offering a geographically unique perspective on viral shedding dynamics. Our findings contribute to a globally relevant understanding of SARS-CoV-2 shedding by revealing differences in shedding durations compared to studies from other regions. These differences highlight the need for geographically diverse research to account for variations in genetic background, immune response, and healthcare practices.

RevDate: 2025-03-27

Wang IC, Buffington SA, R Salas (2024)

Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders.

Current epidemiology reports, 11(4):222-232.

PURPOSE OF REVIEW: Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.

RECENT FINDINGS: The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.

SUMMARY: Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.

RevDate: 2025-03-27
CmpDate: 2025-03-25

Feng Y, Chen W, Chen J, et al (2025)

Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation.

Microbiome, 13(1):83.

OBJECTIVE: Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.

DESIGN: C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.

RESULTS: CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.

CONCLUSIONS: This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.

RevDate: 2025-03-24

Verbiest A, Møller Andersen JH, Hvistendahl MK, et al (2025)

TRANSFERABILITY OF METABOLIC BALANCE STUDIES IN SHORT BOWEL SYNDROME.

Clinical nutrition ESPEN pii:S2405-4577(25)00120-2 [Epub ahead of print].

BACKGROUND: Metabolic balance studies (MBS) are the gold standard method to assess the intestinal absorptive function in patients with short bowel syndrome (SBS). During a full MBS, patients are admitted to the hospital to collect duplicates of all ingested foods and drinks, as well as their fecal and urinary output, typically over a 72-hour period. These collections are further processed to assess absorption of energy, macronutrients (nitrogen, fat and carbohydrate) and electrolytes (sodium, potassium, calcium and magnesium). Full MBS require dedicated laboratory personnel, equipment, knowledge and experience, which explains why they are currently only performed in one center.

AIM: We aimed to explore the transferability of full MBS in patients with SBS from the reference center to a clinical center that was new to and unexperienced in MBS.

METHODS: A collaboration between the centers was initiated to transfer knowledge on how to perform MBS collections, how to process and how to analyze energy, macronutrient and electrolyte content in the collected samples. At practical level, transferability included successful MBS collecting and processing. At analytical level, transferability included the lyophilization of homogenized samples at both centers. The powder that was created at the reference center was measured at both centers to assess the transferability of the analytical methods; while the site-specific powder was measured at the corresponding center to determine full process transferability. The intraclass correlation coefficient (ICC) was calculated to define the absolute agreement between both centers.

RESULTS: A total of 21 MBS were performed in 7 patients with SBS at the new center. A total of 189 samples were collected, equally distributed among combined meals and drinks (n=63), fecal output (n=63) and urinary output (n=63). Meals and drinks samples and fecal output samples were processed in the new center and lyophilized at both centers, with a perfect reliability for dry matter between the centers (ICC = 1). At the level of method transferability, there was an excellent absolute agreement between centers for energy and nitrogen analyses (ICC>0.9). For fat, the mean coefficients of variation (cv) between centers for fecal output (6.3%) and meals and drinks (12.0%) were higher, but ICC showed excellent (0.957) to good (0.787) agreement, respectively. Carbohydrate results differed more between the centers (mean cv of 17.5% for fecal output and 16.4% for meals and drinks), translating into a moderate (meals and drinks, ICC = 0.654) to good (fecal output, ICC = 0.812) reliability. Similar results and degrees of agreement as obtained for the method transferability were observed with the site-specific powder.

CONCLUSION: Our study showed the feasibility of a full MBS transferability to a new unexperienced center with promising agreement of the results obtained between both centers. Our findings aim to inspire other specialized intestinal failure centers to adopt the full MBS methodology for both clinical practice and research purposes.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Tian HL, Wang L, Ma CL, et al (2025)

[Fecal microbiota transplantation for the treatment of intestinal disorders: An analysis of treatment of 15 000 patients].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):296-303.

Objective: To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis. Methods: This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions. Results: At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT. Conclusion: FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Li L, Wang L, Guo GG, et al (2025)

[Evaluation of the efficacy and safety of multi-center fecal microbiota transplantation for treatment of functional constipation: A retrospective real-world study].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):288-295.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment. Methods: This retrospective, multicenter, single-arm, pre-post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m[2], and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups. Results: In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923-0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions: FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Xu Y, Ye C, Li N, et al (2025)

[Challenges and progress in in the clinical application of fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):266-273.

With the deepening understanding of the role of gut microbiota in human health and disease, fecal microbiota transplantation has gained widespread attention as an emerging therapeutic approach in recent years. This technique involves the transplantation of microbial communities from the feces of healthy donors into patients to reconstruct or improve the gut microbiota structure, thereby achieving therapeutic goals. Fecal microbiota transplantation has become an effective method for treating recurrent or refractory Clostridium difficile infections and has shown good therapeutic effects and safety in clinical trials for various gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, slow transit constipation, and chronic diarrhea. Moreover, its application has been extended to research in metabolic diseases and neurological disorders, which are not directly related to the gut. However, the clinical efficacy of fecal microbiota transplantation still needs improvement, and there are many challenges regarding specific application strategies that remain to be addressed. This article discusses the current progress and challenges of fecal microbiota transplantation strategies and reviews cutting-edge interventional methods such as small intestine microbiota intervention and bacteriophage therapy, aiming to provide reference for further research in fecal microbiota transplantation.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Jin YF, Wen WJ, T Zuo (2025)

[Phages in human health and gut microbiota transplantation therapy].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):261-265.

Phages, prokaryotic viruses widely present in the human, are a crucial component of the gut microbiome. They play a significant role in human health and the development of diseases. Emerging evidence indicates that phages can interact with bacteria to affect their abundance, metabolism, and antibiotic resistance, thereby influencing the balance of the gut microbiota. In addition, phages also contribute to the gut immune response, and can become dysregulated in a range of immune-related diseases. Gut phages also carry important roles in fecal microbiota transplantation (FMT) for disease treatment. Phages can target specific bacterial members and communities, thereby reduce the risk of bacterial infections or the presence of bacteria, and maintain the stability of the gut microbiome. However, gut phageome research is still in its infancy and additional basic and clinical researches are required to evaluate its species composition, mechanisms of pathogenicity or protection, as well as its efficacy and safety.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Wang XJ, Zhao D, Qin YH, et al (2025)

[How close is fecal microbiota transplantation to moving to precision medicine?].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):254-260.

Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Parenteral and Enteral Nutrition Branch of the Chinese Medical Association, Chinese Society for the Promotion of Human Health Science and Technology, Committee on Gut Microecology and Fecal Microbiota Transplantation, Shanghai Preventive Medicine Association (2025)

[Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 28(3):225-235.

In recent years, significant progress has been made in the clinical and basic research on fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). With the continuous application of new microbiota-based diagnostic and therapeutic concepts in clinical practice, it is imperative to standardize the diagnostic and therapeutic processes of FMT for IBD and provide consensus recommendations based on the latest evidence from evidence-based medicine for clinical practitioners. Organized by the Chinese Society for Parenteral and Enteral Nutrition of the Chinese Medical Association, the Gut Microbiota and FMT Committee of the Chinese Society for Human Health Sciences, and the Gut Microbiota Committee of the Shanghai Preventive Medicine Association, and with reference to the latest international consensus and relevant research advancements, this consensus integrates the clinical practice experience of domestic experts to establish the "Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)". This consensus provides 29 recommendations focusing on the selection of FMT indications, gut microbiota analysis, donor selection and quality control for IBD transplantation, considerations during the transplantation period, selection of transplantation routes and dosages, management of FMT-related complications, and future research directions, aiming to offer standardized guidance for the clinical application of FMT in the treatment of IBD.

RevDate: 2025-03-23

González-Correa C, Moleón J, Miñano S, et al (2025)

Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.

Phytotherapy research : PTR [Epub ahead of print].

The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.

RevDate: 2025-03-23

Su R, Wen W, Jin Y, et al (2025)

Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.

Gut pii:gutjnl-2024-334516 [Epub ahead of print].

BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.

OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.

DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.

RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.

CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.

RevDate: 2025-03-22

Xu DQ, Geng JX, Gao ZK, et al (2025)

To explore the potential combined treatment strategy for colorectal cancer: inhibition of cancer stem cells and enhancement of intestinal immune microenvironment.

European journal of pharmacology pii:S0014-2999(25)00287-0 [Epub ahead of print].

BACKGROUND: The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

METHODS: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

RESULTS: In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8[+] T cells and Ly6G[+] neutrophils, as well as reducing F4/80[+] macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

CONCLUSIONS: Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.

RevDate: 2025-03-22

Luo F, Yang J, Song Z, et al (2025)

Renshen Zhuye decoction ameliorates high-fat diet-induced obesity and insulin resistance by modulating gut microbiota and metabolic homeostasis.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 141:156655 pii:S0944-7113(25)00295-8 [Epub ahead of print].

BACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.

PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.

METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.

RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.

CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.

RevDate: 2025-03-22

Gao C, Chen Y, Zhang Z, et al (2025)

LAYING RATE WAS CORRELATED WITH MICROBIAL Fecal microbiota transplantation improves the laying performance by changing the gut microbiota composition in late laying period.

Poultry science, 104(5):105064 pii:S0032-5791(25)00303-7 [Epub ahead of print].

This research investigated the differences and succession patterns of microbes in different ages, the performance of laying hens, and the effect of Fecal Microbiota Transplantation (FMT) on aged laying hens. First, based on the different laying rates and age, we divided the laying hens into four groups: 75-week-old high-yield (OH, laying rate (LR) > 90%), 75-week-old low-yield (OL, LR < 60%), 75-week-old non-laying hens (OZ, LR = 0%) and 35-week-old high-yield (YH, LR > 90%) with 5 replicates in each group and 6 chickens in each replicate. The microbial metabolic patterns between different ages and laying rates were determined using 16S rDNA technology. Then, to verify the results of microbiome research, we utilized FMT technology to transplant the gut microbiota from OH to OZ (OZFMT-OH), thereby revealing the connection between gut microbes and production performance. The results showed that high-yielding hens (YH and OH groups) had higher levels of Superoxide dismutase (SOD) and Immunoglobulin A (IgA) compared to OL and OZ groups. The Villus height to Crypt depth ratio(V/C) was significantly higher in the YH group than in 75-week-old hens (P < 0.05). Alpha diversity indicated higher microbial diversity in the YH group compared to older hens (P < 0.05), with YH hens harboring more Megamonas, OH hens more Bacteroides, and OL and OZ groups showing higher levels of harmful bacteria. The villus height, V/C, mucosal layer thickness, cup cell number acetic acid level, and LR in the OZFMT-OH group were significantly higher than those in the OZ group (P < 0.05), while the IL-2 level, crypt depth and cecal intestinal wall thickness were significantly lower than those in OZ group (P < 0.05). FMT also changed the morphological structure of grade follicles and small yellow follicles, improved the microbe composition of cecum and increased Bacteroides abundance. In the late laying period, if the intestinal flora cannot maintain the dynamic balance and carry out timely replacement, the production performance may be decreased, and the increase of Bacteroides abundance in the intestinal tract can improve the intestinal health and production performance of laying hens in the late laying period.

RevDate: 2025-03-23

Zhang J, Zhou J, He Z, et al (2025)

Salidroside attenuates NASH through regulating bile acid-FXR/TGR5 signaling pathway via targeting gut microbiota.

International journal of biological macromolecules, 307(Pt 4):142276 pii:S0141-8130(25)02828-4 [Epub ahead of print].

Nonalcoholic steatohepatitis (NASH) is a significant threat to human health. Our previous study revealed that salidroside attenuated NASH and regulated the gut microbiota. However, whether the therapeutic effect of salidroside depends on gut microbiota remains to be determined. Therefore, we conducted further experiments to elucidate the essential functions of gut microbiota-associated metabolic pathways in the anti-NASH effects of salidroside. Our results showed that salidroside effectively alleviated lipid accumulation and inflammatory injury in NASH mice. 16S rRNA sequencing revealed that salidroside increased the abundance of Bacteroides. Mice receiving fecal microbiota transplantation (FMT) from salidroside-treated also presented less hepatic steatosis and higher abundance of Bacteroides. Antibiotics eliminated the effects of salidroside on hepatic steatosis and the gut microbiota. Mechanistically, salidroside and FMT from salidroside-treated altered the bile acid (BA) profile by decreasing the levels of conjugated BAs and tauro-α/β-muricholic acid and activated downstream farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Furthermore, we found that inhibitors of bile salt hydrolase (BSH) and FXR/TGR5 abolished the effects of salidroside and reduced downstream carnitine palmitoyltransferase 1α and lipoprotein lipase expression. These data demonstrate that salidroside attenuated NASH via gut microbiota-BA-FXR/TGR5 signaling pathway and reveal the underlying mechanism of salidroside on NASH.

RevDate: 2025-03-22

Wu S, Qiao L, Liu H, et al (2025)

Age related gut microbiota regulates energy-related metabolism to influence natural aging phenotypes in the heart.

Experimental gerontology, 203:112734 pii:S0531-5565(25)00063-4 [Epub ahead of print].

As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study aimed to explore the roles and mechanisms of the gut microbiota and related metabolites in the natural aging of the heart. Animal models of fecal microbiota transplantation (FMT) were established in elderly and young rats. 16S rRNA sequencing revealed that the gut microbiota of the recipients shifted toward the profile of the donors, with concomitant cardiac structure and diastolic function changes detected via ultrasound and positron emission tomography-computed tomography (PET-CT). A group of significantly enriched myocardial metabolites detected by LC/MS were involved in the fatty acid β-oxidation process. Together with altered glucose uptake, as revealed by PET-CT, changes in ATP content and mitochondrial structure further verified a metabolic difference related to energy among rats transplanted with the gut microbiota from donors of different ages. This study demonstrated that gut microbes may participate in the physiological aging process of the rat heart by regulating oxidative stress and autophagy. The gut microbiota has been shown to be involved in the natural aging of the heart at multiple levels, from the organ level to the metabolically plastic myocardiocytes and associated molecules.

RevDate: 2025-03-25

Chinna Meyyappan A, Sgarbossa C, Bromley H, et al (2025)

The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuité et efficacité du traitement de l'écosystème microbien (met-2) dans la dépression majeure - une étude de phase 2 à double insu contrölée par placebo : résultats cliniques.

Canadian journal of psychiatry. Revue canadienne de psychiatrie [Epub ahead of print].

ObjectivesThis study examines the safety and efficacy of a fecal transplant alternative, Microbial Ecosystem Therapeutic-2 (MET-2), in improving symptoms of depression. The primary objective of this study is to assess changes in depressive symptoms before, during, and after administration of MET-2 in comparison to placebo. Mood-related symptoms such as anxiety and anhedonia, gastrointestinal symptoms, and safety of the therapeutic were also assessed using both self-report and clinician-rated measures.MethodsTwenty-nine participants (n = 29) experiencing a major depressive episode were recruited from the Kingston and Toronto areas. Participants orally consumed MET-2, an encapsulated microbial therapeutic containing 40 different strains of bacteria, or placebo alternative, once daily for 6 weeks with a 2-week follow-up. Participants underwent a series of clinical assessments used to measure mood, anxiety, and gastrointestinal symptoms.ResultsThere was a significant improvement in depressive symptomology over time as determined by Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001); however there was no significant difference between placebo and MET-2 groups (p = 0.338). No serious adverse events were reported. The findings of this study are the first to provide evidence for the role of oral microbial therapeutics, such as MET-2, as treatment for symptoms of depression.ConclusionsThough there are positive trends suggesting a greater improvement in depressive symptomology among the MET-2 group compared to the placebo group, a larger sample size is needed for more conclusive results. Clinicaltrials.gov NCT04602715.

RevDate: 2025-03-21

Prati D, Caprioli F, Stea L, et al (2025)

A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs.

Blood transfusion = Trasfusione del sangue pii:BloodTransfus.929 [Epub ahead of print].

Fecal Microbiota Transplantation (FMT) is an innovative therapy with growing applications, particularly for recurrent Clostridioides difficile infections (rCDI). However, the broader use of FMT is challenged by the complexities of donor recruitment, the necessity of stringent screening protocols, and the need for maintaining high-quality stool biobanks. This paper explores the integration of FMT programs within transfusion medicine departments, taking advantage of their expertise in donor management and biological material processing. Despite the complexities of donor screening, including a low eligibility rate, the collaboration between transfusion services and other hospital departments demonstrates a viable model for expanding FMT access. Additionally, the recent EU regulations on substances of human origin (SoHO) offer a framework for standardizing and scaling stool banking, enhancing the safety and efficacy of FMT procedures.

RevDate: 2025-03-21

Yang Y, Zhang Y, Zhang W, et al (2025)

Flammulina velutipes residue Polysaccharide Alleviates Immunosuppression and Intestinal Injury by Modulating Gut Microbiota and Associated Metabolites.

Journal of agricultural and food chemistry [Epub ahead of print].

This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.

RevDate: 2025-03-22

Waterman A, Doumas SA, Fischer M, et al (2025)

Uncovering the Hidden Link Between the Aberrant Intestinal Microbiome and Fibromyalgia.

Gastroenterology & hepatology, 21(2):111-121.

Fibromyalgia is a multifaceted syndrome primarily characterized by chronic widespread pain and fatigue. Despite its significant prevalence and incidence, the mechanisms mediating the disease pathogenesis have remained poorly understood; however, increasing evidence suggests a potentially central role of intestinal dysbiosis. Researchers have been examining possible diagnostic biomarkers, such as Helicobacter pylori infection, urine metabolite profiles, and cytokine levels, which reflect these microbiome changes. Additionally, evaluation of therapeutic interventions targeting the gut microbiome, including probiotics, fecal microbiota transplantation, and antibiotics for specific infections, has highlighted their potential in alleviating fibromyalgia symptoms. This article delves into the emerging role of the gut microbiome in fibromyalgia pathogenesis, illustrating how alterations in gut bacterial composition and diversity are implicated in the pathophysiology of the disease through the gut-brain axis, and sets a direction for future research to enhance diagnostic accuracy and therapeutic efficacy of this complex condition.

RevDate: 2025-03-20
CmpDate: 2025-03-20

Vernon JJ (2025)

Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.

Advances in experimental medicine and biology, 1472:277-294.

The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.

RevDate: 2025-03-21

Zhu B, Gu Z, Hu H, et al (2025)

Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation.

Research (Washington, D.C.), 8:0636.

Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.

RevDate: 2025-03-21

Zhang C, Wang Y, Cheng L, et al (2025)

Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response.

Frontiers in oncology, 15:1557959.

Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.

RevDate: 2025-03-21
CmpDate: 2025-03-20

Cai S, Li Z, Bai J, et al (2025)

Optimized oxygen therapy improves sleep deprivation-induced cardiac dysfunction through gut microbiota.

Frontiers in cellular and infection microbiology, 15:1522431.

Adequate sleep is of paramount importance for relieving stress and restoring mental vigor. However, the adverse physiological and pathological responses resulting from sleep insufficiency or sleep deprivation (SD) are becoming increasingly prevalent. Currently, the impact of sleep deficiency on gut microbiota and microbiota-associated human diseases, especially cardiac diseases, remains controversial. Here, we employed the following methods: constructed an experimental sleep-deprivation model in mice; conducted 16S rRNA sequencing to investigate the changes in gut microbiota; through fecal microbiota transplantation (FMT) experiments, transplanted fecal microbiota from sleep-deprived mice to other mice; established an environment with a 30% oxygen concentration to explore the therapeutic effects of oxygen therapy on gut microbiota-associated cardiac fibrosis and dysfunction; and utilized transcriptome data to study the underlying mechanisms of oxygen therapy. The results revealed that: sleep-deprived mice exhibited weakness, depression-like behaviors, and dysfunction in multiple organs. Pathogenic cardiac hypertrophy and fibrosis occurred in sleep-deprived mice, accompanied by poor ejection fraction and fractional shortening. 16S rRNA sequencing indicated that sleep deprivation induced pathogenic effects on gut microbiota, and similar phenomena were also observed in mice that received fecal microbiota from sleep-deprived mice in the FMT experiments. The environment with a 30% oxygen concentration effectively alleviated the pathological impacts on cardiac function. Transcriptome data showed that oxygen therapy targeted several hypoxia-dependent pathways and inhibited the production of cardiac collagen. In conclusion, these results demonstrate the significance of sufficient sleep for gut microbiota and may represent a potential therapeutic strategy, where the oxygen environment exerts a protective effect on insomniacs through gut microbiota.

RevDate: 2025-03-24
CmpDate: 2025-03-24

Nagy M, Wychera C, Schemm J, et al (2025)

Bacterial and Parasitic Stool Studies Have Limited Utility in Pediatric Hematopoietic Stem Cell Transplant Patients.

Pediatric blood & cancer, 72(5):e31617.

BACKGROUND: Diarrhea is a common complication among pediatric hematopoietic stem cell transplantation (HCT) recipients. Although many of the cases are secondary to graft-versus-host disease (GVHD), stool microbiological studies are often performed to evaluate an underlying infectious etiology. The aim of this study was to assess the frequency and utility of stool studies in children who have undergone HCT.

METHODS: Demographics, clinical characteristics, and stool study results (viral, parasitic, and bacterial) of all patients who underwent HCT at a large, academic, freestanding children's hospital between January 2006 and December 2023 were obtained. Statistical analysis conducted included t tests, chi-square, and linear regression.

RESULTS: Overall, 1381 HCT recipients (9.2 ± 6.6 years) were included. Altogether, 6509 stool studies were obtained among 741 (54%) patients. Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli (SSYCE) studies were sent on 363 (26%, 2252 studies) patients with 1 (0.04%) positive result. Clostridium difficile was sent on 706 (51%, 2055 studies) patients, with 156 positive studies (7.6%). Stool ova and parasite testing was sent on 143 (10%, 242 studies) patients, with two positive results (0.8%). Viral studies were sent on 638 (46%, 1960 studies) patients, with 107 positive studies (5.5%).

CONCLUSIONS: While testing for Clostridium difficile and enteric viruses may have value in the work-up of pediatric HCT patients, SSYCE and O&P studies hold little to no value. Clinical practices surrounding routine stool microbiological studies should be reconsidered.

RevDate: 2025-03-19

Xue M, Deng Q, Deng L, et al (2025)

Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review.

European journal of pharmacology pii:S0014-2999(25)00275-4 [Epub ahead of print].

Psoriasis is a chronic, recurrent and systemic inflammatory skin disease which is mediated by immunoreaction. Its pathogenesis is multifactorial, and the exact driving factor remains unclear. Recent studies showed that gut microbiota, which maintain immune homeostasis of our bodies, is closely related with occurrence, development and prognosis of psoriasis. The intestinal microbial abundance and diversity in patients with psoriasis have changed significantly, including intestinal microbiota disorders and reduced production of short chain fatty acids (SCFAs), abnormalities in Firmicutes/Bacteroidetes (F/B), etc. Besides, the intestinal microbiota of psoriasis patients has also changed after treatment of systemic drugs, biologics and small molecule chemical drugs, suggesting that the intestinal microbiota may be a potential response-to-treatment biomarker for evaluating treatment effectiveness. Oral probiotics and prebiotics administration as well as fecal microbial transplantation were also reported to benefit well in psoriasis patients. Additionally, we also discussed the microbial changes from the skin and other organs, which regulated both the onset and treatment of psoriasis together with gut microbiota. Herein, we reviewed recent studies on the psoriasis-related microbiota in an attempt to confidently identify the "core" microbiota of psoriatic patients, understand how microbiota influence psoriasis through the gut-skin axis, and explore potential therapeutic strategies for psoriasis.

RevDate: 2025-03-20

Gu C, Sha G, Zeng B, et al (2025)

Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy.

Therapeutic advances in gastroenterology, 18:17562848251327167.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.

RevDate: 2025-03-20

Sharma P, Jain T, Sorgen A, et al (2025)

Smoking-induced gut microbial dysbiosis mediates cancer progression through modulation of anti-tumor immune response.

iScience, 28(3):112002.

Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.

RevDate: 2025-03-20

Hirsch W, Fischer M, Khoruts A, et al (2025)

Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Multicenter Observational Study.

Open forum infectious diseases, 12(3):ofaf130.

BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.

METHODS: This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration.

RESULTS: The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis.

CONCLUSIONS: Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.

RevDate: 2025-03-22
CmpDate: 2025-03-18

Deng Z, Mei S, Ouyang Z, et al (2025)

Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.

Gut microbes, 17(1):2476561.

The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.

RevDate: 2025-03-20
CmpDate: 2025-03-18

Xiao P, Li Y, Li X, et al (2025)

Long-term safety of fecal microbiota transplantation in Chinese children from 2013 to 2023: a single-center retrospective study.

BMC microbiology, 25(1):152.

BACKGROUND: The gut microbiome plays a vital role in influencing various health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a rapid, safe, and effective method for modifying the microbiome. However, there is a lack of long-term safety data regarding FMT in children. This study presents the largest single-center analysis of the long-term safety outcomes of FMT in pediatric patients in China, featuring a substantial sample size and an extended follow-up period to thoroughly examine its safety in children.

METHODS: A retrospective study was conducted on 813 patients who underwent FMT treatments at our hospital from December 2013 to December 2023. All FMT procedures adhered to standardized protocols. The safety of these treatments was retrospectively assessed, focusing on adverse events (AEs) and serious adverse events (SAEs). AEs associated with FMT were categorized as short-term (within 48 h post-FMT) and long-term (within 3 months). Various potential influencing factors for AEs, including sex, age, route of administration, disease type, and consanguineous donor, were examined as independent variables. Significant independent factors and their associated risk ratios with 95% confidence intervals (CI) were determined through multivariate logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.

RESULTS: A total of 813 patients underwent FMT, with a median age of 93 months (range 4-215) and 68.0% being males. The average follow-up time was 32.3 months (range 1-122). All short-term AEs resolved within 48 h, with an overall occurrence rate of 5.8% (47/813). The most common short-term AEs included vomiting (2.0%), abdominal pain (1.6%), diarrhea (0.9%), fever (0.7%), dysphoria (0.4%), and nausea (0.4%). Multivariable analysis revealed that patients with inflammatory bowel disease (IBD) (OR: 3.98, 95% CI: 1.78-8.92, P = 0.001) and those who received FMT via capsules (OR: 0.09, 95% CI: 0.03-0.27, P = 0.000) were independent risk factors for FMT-related AEs. All 813 patients were followed up for at least 1 month, with 78.8% followed for more than 12 months. No long-term AEs occurred during the longest follow-up period of 122 months.

CONCLUSIONS: FMT is a promising treatment option that appears to be safe and well tolerated. This study stands out for its substantial sample size, making it's the largest reported series in pediatrics, as well as for having the longest follow-up period for FMT in this population.

CLINICAL TRIAL NUMBER: Not applicable.

RevDate: 2025-03-20

Oami T, Shimazui T, Yumoto T, et al (2025)

Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets.

Journal of intensive care, 13(1):16.

BACKGROUND: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

MAIN BODY: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

CONCLUSION: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.

RevDate: 2025-03-20

Li L, Li T, Liang X, et al (2025)

A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.

Cell discovery, 11(1):25.

According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.

RevDate: 2025-03-20
CmpDate: 2025-03-17

Dongre DS, Saha UB, SD Saroj (2025)

Exploring the role of gut microbiota in antibiotic resistance and prevention.

Annals of medicine, 57(1):2478317.

BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.

RevDate: 2025-03-17
CmpDate: 2025-03-17

Newsome RC, McGriff C, Gharaibeh RZ, et al (2025)

Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice.

Journal of visualized experiments : JoVE.

Germ-free mice are an important investigation tool for understanding the contribution of microorganisms in host health and disease, enabling assessment of the specific role of individuals, defined or complex groups of microorganisms in host response. Traditionally bred and reared in flexible-film or semi-rigid isolators, germ-free mouse husbandry and experimental manipulation are costly and require numerous trained staff and a large space footprint in animal housing facilities. The IsoPositive caging system allows for experimental manipulation of germ-free mice in individual, hermetically-sealed, positive-pressure isolator cages (isocages), reducing cost and enabling greater flexibility in experimental manipulations. Here, a protocol is described for transferring germ-free mice from breeding isolators to isocages and subsequent fecal transfer from human donor stool into mice to create stable long-term gut "humanized" mice for future studies. The materials and preparation needed for the utilization of the isocage system are described, including the use of chlorine-dioxide sterilant chemical sterilant to clean cages, supplies, equipment, and personal protective equipment. The methods for confirming the germ-free status of transferred mice and how to determine contamination in the caging system are discussed. The procedure for husbandry, including bedding, food, and water supply, is further discussed. The protocol for human fecal slurry preparation and gavage into germ-free mice to create gut "humanized" mice, along with stool collection to monitor the microbial community composition of these mice, are described. An experiment illustrates that two weeks post-human fecal transplant allows for stable colonization of donor microbiota in the murine hosts, enabling subsequent experimental usage. Furthermore, the collection of humanized mouse feces in viability preservation media, enabling use in further functional experiments, is described. Overall, these methods allow for the safe and effective establishment of humanized mouse communities in experimental gnotobiotic cages for further manipulation.

RevDate: 2025-03-18

Wang X, Wang WY, Yu XL, et al (2025)

Comprehensive review of Clostridium difficile infection: Epidemiology, diagnosis, prevention, and treatment.

World journal of gastrointestinal pharmacology and therapeutics, 16(1):100560.

In recent years, nosocomial infections caused by Clostridium difficile (C. difficile) have risen, becoming a leading cause of hospital-acquired diarrhea. The global prevalence of C. difficile infection (CDI) varies across regions and populations. The diagnosis relies primarily on laboratory testing, including toxin, glutamate dehydrogenase, and nucleic acid amplification tests. Treatment strategies for CDI include antimicrobial therapy (e.g., metronidazole, vancomycin, and fidamycin), fecal transplantation, and immunotherapy (e.g., belotozumab), depending on the patient's specificity and severity. This paper reviews recent research on CDI's epidemiological characteristics, risk factors, diagnosis, treatment, and prevention, aiming to support hospitals and public health initiatives in implementing effective detection, prevention, and treatment strategies.

RevDate: 2025-03-17

Le PH, Chen CL, Kuo CJ, et al (2025)

Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.

RevDate: 2025-03-19
CmpDate: 2025-03-17

Liu Y, Liu J, Ren R, et al (2025)

Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m[6]A in white adipose tissue by gut microbiota.

Microbiome, 13(1):75.

BACKGROUND: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

RESULTS: Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m[6]A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m[6]A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m[6]A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m[6]A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.

CONCLUSIONS: Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m[6]A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.

RevDate: 2025-03-15

Fan J, Wu Y, Wang X, et al (2025)

The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis.

Journal of advanced research pii:S2090-1232(25)00177-8 [Epub ahead of print].

INTRODUCTION: The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

OBJECTIVES: This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

METHODS: Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

RESULTS: GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

CONCLUSIONS: L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.

RevDate: 2025-03-16

Hajjeh O, Rajab I, Bdair M, et al (2025)

Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease.

Neuroscience, 572:232-247 pii:S0306-4522(25)00216-7 [Epub ahead of print].

The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.

RevDate: 2025-03-15
CmpDate: 2025-03-15

Lin D, Howard A, Raihane AS, et al (2025)

Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes.

Current neurology and neuroscience reports, 25(1):23.

PURPOSE OF REVIEW: A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

RECENT FINDINGS: The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin and even a collection of poetry — Chicago Poems by Carl Sandburg.

Timelines

ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.

Biographies

Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 28 JUL 2024 )