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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 03 May 2025 at 01:48 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: 2025-04-30

Jiang ZM, Fang ZY, Yang X, et al (2025)

Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 142:156745 pii:S0944-7113(25)00384-8 [Epub ahead of print].

BACKGROUND: Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.

PURPOSE: This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.

RESULTS: This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.

CONCLUSION: The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.

RevDate: 2025-04-30

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

Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation.

The ISME journal pii:8123333 [Epub ahead of print].

Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced Akkermansia muciniphila levels. Contrary to expectations, Akkermansia muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, post-radiation Akkermansia muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables Akkermansia muciniphila to use mucin as an energy source. Additionally, Akkermansia muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of Akkermansia muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.

RevDate: 2025-05-02
CmpDate: 2025-04-30

Alves Costa Silva C, Almonte AA, L Zitvogel (2025)

Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes.

Biomolecules, 15(4):.

Growing evidence suggests that cancer should not be viewed solely as a genetic disease but also as the result of functional defects in the metaorganism, including disturbances in the gut microbiota (i.e., gut dysbiosis). The human microbiota plays a critical role in regulating epithelial barrier function in the gut, airways, and skin, along with host metabolism and systemic immune responses against microbes and cancer. Collaborative international networks, such as ONCOBIOME, are essential in advancing research equity and building microbiome resources to identify and validate microbiota-related biomarkers and therapies. In this review, we explore the intricate relationship between the microbiome, metabolism, and cancer immunity, and we propose microbiota-based strategies to improve outcomes for individuals at risk of developing cancer or living with the disease.

RevDate: 2025-05-02

Alum EU, Uti DE, Ugwu OP, et al (2025)

Unveiling the microbial orchestra: exploring the role of microbiota in cancer development and treatment.

Discover oncology, 16(1):646.

The human microbiota comprises a diverse microbial ecosystem that significantly impacts health and disease. Among its components, the gut microbiota plays a crucial role in regulating metabolic, immunologic, and inflammatory responses. Dysbiosis, an imbalance in microbial composition, has been linked to carcinogenesis through mechanisms such as chronic inflammation, metabolic disturbances, epigenetic modifications, and immune system dysregulation. Additionally, dysbiosis influences the efficacy and toxicity of cancer therapies. Given these associations, there is growing interest in leveraging the microbiota as a biomarker for cancer detection and outcome prediction. Notably, distinct microbial signatures have been identified across various cancer types, suggesting their potential as diagnostic markers. Furthermore, modulation of the microbiota presents a promising avenue for improving cancer treatment outcomes through strategies such as antibiotics, prebiotics, probiotics, fecal microbiota transplantation, dietary interventions, small-molecule inhibitors, and phage therapy. To explore these relationships, we conducted a comprehensive literature review using Web of Science, Scopus, PubMed, MEDLINE, Embase, and Google Scholar as our primary online databases, focusing on indexed peer-reviewed articles up to the present year. This review aims to elucidate the role of dysbiosis in cancer development, examine the molecular mechanisms involved, and assess the impact of microbiota on cancer therapies. Additionally, we highlight microbiota-based therapeutic strategies and discuss their potential applications in cancer management. A deeper understanding of the intricate interplay between the microbiota and cancer may pave the way for novel approaches to cancer prevention, early detection, and treatment optimization.

RevDate: 2025-04-30
CmpDate: 2025-04-30

Hoffmann DE, Javitt GH, Kelly CR, et al (2025)

Fecal microbiota transplantation: a tale of two regulatory pathways.

Gut microbes, 17(1):2493901.

Fecal microbiota transplantation (FMT) is a procedure involving the transfer of intestinal microbiota from a healthy donor to a patient to restore a functional intestinal microbiome. First described in modern science in 1958, the use of FMT has been practiced for decades, but only during the past dozen years have clinical frameworks and legal regulations from competent authorities been developed. Future development of microbiota-derived medical therapies will be shaped by the regulatory frameworks of various jurisdictions. This review examines the historical development and status of FMT regulations in the United States and Europe, with particular attention to their respective approaches to ensuring the safety and quality of the therapeutic product and patient access.

RevDate: 2025-04-29

Liu X, Cui J, Tan X, et al (2025)

Short-Chain Fatty Acids Alleviate Perioperative Neurocognitive Disorders Through BDNF/PI3K/Akt Pathway in Middle-Aged Rats.

Molecular neurobiology [Epub ahead of print].

Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3-V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation-all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management.

RevDate: 2025-04-29

Kamath S, Bryant RV, Costello SP, et al (2025)

Translational strategies for oral delivery of faecal microbiota transplantation.

Gut pii:gutjnl-2025-335077 [Epub ahead of print].

Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.

RevDate: 2025-04-29
CmpDate: 2025-04-30

Almonte AA, L Zitvogel (2025)

Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.

Journal for immunotherapy of cancer, 13(4): pii:jitc-2025-011540.

Immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies, depend heavily on a healthy and diverse gut microbiome for optimal efficacy. Dysbiosis, or an imbalance in gut microbial composition and function, can diminish immunotherapy responses by altering immune cell trafficking and metabolic output. Key microbial metabolites such as short-chain fatty acids and modified bile acids shape host immunity and influence T-cell function, while their disruption can foster an immunosuppressive microenvironment. Emerging strategies to restore a balanced microbiome and boost treatment outcomes include dietary interventions, supplementation with beneficial microbes, and fecal microbiota transplantation. Despite these advances, challenges remain in defining dysbiosis, identifying reliable biomarkers, and tailoring microbiota-centered interventions. Nevertheless, as our understanding evolves, the gut microbiome holds promise as an integral component of personalized cancer immunotherapy.

RevDate: 2025-05-01

Mahmoud AA, Wang X, Liao X, et al (2025)

Impact of prophages on gut microbiota and disease associations.

Microbial pathogenesis, 204:107642 pii:S0882-4010(25)00367-5 [Epub ahead of print].

The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.

RevDate: 2025-05-01
CmpDate: 2025-04-30

De Sabato L, Ianiro G, Alborali GL, et al (2023)

Molecular Characterization and Phylogenetic Analysis of Hepatitis E Virus (HEV) Strains from Pigs Farmed in Eight European Countries between 2020 and 2022.

Transboundary and emerging diseases, 2023:2806835.

In high-income countries, the hepatitis E virus (HEV) is considered an emerging threat causing autochthonous acute hepatitis in humans, with an increased number of reported cases over the last 10 years and related increased burden of chronic hepatitis in immunocompromised and transplant patients. Pigs are the main reservoir of the HEV-3 genotype, which is the most common in Europe, and can be transmitted to humans through the consumption of raw and undercooked pork products. Extensive sequencing revealed the existence of several HEV-3 subtypes in both humans and pigs, confirming a broad heterogeneity of the virus, with some subtypes, such as 3e, 3f, and 3c, which are predominant in Europe. In this study, 291 HEV sequences were obtained from pig feces sampled in more than 74 farms located in Austria, Bulgaria, Czech Republic, Germany, Italy, Poland, the United Kingdom, as well as an unknown number of farms in Netherlands. Of the 99 nonidentical sequences (99/291), 90 were assigned to seven established HEV-3 subtypes: 3a, 3c, 3e, 3f, 3g (here named 3g-like), 3i, and 3l (named 3l-like), already described in Europe, while nine sequences of HEV-3 could not be assigned to any existing subtype (here named 3 [∗]). The 3e subtype was the most common, detected in six out of eight countries, followed by 3f and 3c, which were also present in several countries; 3g-like, 3i, and 3l-like subtypes showed only a limited circulation. The distribution of frequently (3e, 3f, and 3c) and rarely (3g-like, 3i, and 3l-like) detected HEV-3 subtypes in pigs was correlated with their detection rates in human patients in Europe. The results from this study confirm the wide circulation of several HEV-3 strains in European pigs and confirm that sequencing is needed to monitor the different strains and to identify possible zoonotic transmission paths.

RevDate: 2025-04-29

Liu Z, Zhang H, Wang J, et al (2025)

Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis.

Microbiological research, 297:128191 pii:S0944-5013(25)00147-8 [Epub ahead of print].

The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1[-/-]) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1[-/-] mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.

RevDate: 2025-04-29

Cao J, Wang X, Lei Y, et al (2025)

Health Risks of Low-Dose Dietary Exposure to Triphenyl Phosphate and Diphenyl Phosphate in Mice: Insights from the Gut-Liver Axis.

Environmental science & technology [Epub ahead of print].

Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine the health risks associated with exposure to triphenyl phosphate (TPHP) and its metabolite diphenyl phosphate (DPHP). Here, C57BL/6J male mice were exposed to TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 and 7 μg/kg bw/day. TPHP intake affected the levels of short-chain fatty acids and bile acids in the gut, enhancing the production of 29 medium- and long-chain fatty acids in the liver by 3.72-fold and significantly increasing hepatic lipid and cholesterol levels. Metabolomic and molecular analysis confirmed that elevated liver cholesterol levels persisted after an 8 week recovery period. Gut microbiota-dependent cholesterol alterations were the toxic end points observed in TPHP-fed mice, as supported by the results of fecal microbiota transplantation. In DPHP-fed mice, serotonergic and glutamatergic synapses were simultaneously altered in the liver and intestine, corresponding to the reduction of five brain neurotransmitters (15.4-60.8%). Decreased liver carbohydrate levels and insulin resistance were observed in the DPHP-fed mice. These results suggest that TPHP and DPHP affect metabolism via different toxic modes, mediated through the gut-liver axis, providing novel insights into the mechanisms of organophosphate-ester-mediated metabolic disruption.

RevDate: 2025-05-01

Eslami M, Adampour Z, Fadaee Dowlat B, et al (2025)

A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.

Biomedicines, 13(4):.

The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.

RevDate: 2025-05-01

Hauser G, Benjak Horvat I, Rajilić-Stojanović M, et al (2025)

Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.

Biomedicines, 13(4):.

Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.

RevDate: 2025-04-29

Gao X, Fu N, Ben Q, et al (2025)

A Meta-Analysis of the Effects of Gut Microbiota-Based Interventions on Gastrointestinal and Behavioral Symptoms in Children With Autism Spectrum Disorder.

Nutrition reviews pii:8121820 [Epub ahead of print].

CONTEXT: Despite an increasing body of research showing gut microbiota-based interventions can improve gastrointestinal (GI) symptoms and behavioral symptoms in both humans and animals, there are still disagreements about its impact on autism spectrum disorder (ASD) in children.

OBJECTIVE: The goal of this systematic review and meta-analysis was to fully investigate the effects of gut microbiota-based interventions (eg, fecal microbiota transplantation, probiotics, prebiotics) on GI and behavioral symptoms in children with ASD.

DATA SOURCES: The PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Scopus databases were searched from inception to August 25, 2024.

DATA EXTRACTION: Data were extracted by 2 reviewers independently, and discrepancies in authors' judgments were resolved by discussion or consulting a third author.

DATA ANALYSIS: The scale score of GI and behavioral symptoms before and after the intervention was extracted from included trials to evaluate the therapeutic effects of gut microbiota-based therapy in children with autism.

RESULTS: A total of 5722 records were identified, of which 13 included in narrative synthesis and 8 studies included a meta-analysis. The nonsignificant overall effect size of gut microbiota-based intervention on GI symptoms (standardized mean difference [SMD] = -0.34 [95% CI, -0.76 to 0.07]; P = .11) and behavioral symptoms (SMD = -0.18 [95% CI, -0.37 to 0.02]; P = .08) was observed. Nevertheless, we observed a significant effect size on behavioral symptoms in the subgroup of the intervention duration (SMD = -0.26 [95% CI, -0.49 to -0.03]; P = .02).

CONCLUSIONS: In children with autism, the proof supporting the validity of gut microbiota-based intervention on GI and behavioral symptoms should be interpreted cautiously. More randomized controlled trials with rigorous methodological quality are required to precisely confirm the curative benefits of gut microbiota-based interventions on GI and behavioral symptoms in children with autism.

PROSPERO registration no. CRD42024583213.

RevDate: 2025-04-29

Cusumano G, Flores GA, Venanzoni R, et al (2025)

The Impact of Antibiotic Therapy on Intestinal Microbiota: Dysbiosis, Antibiotic Resistance, and Restoration Strategies.

Antibiotics (Basel, Switzerland), 14(4):.

The human gut microbiota-an intricate and dynamic ecosystem-plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota-gut-brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions-such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics-have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis.

RevDate: 2025-04-30
CmpDate: 2025-04-29

Pei X, Liu L, Y Han (2025)

Advances in human microbiome and prostate cancer research.

Frontiers in immunology, 16:1576679.

Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.

RevDate: 2025-04-30

Nguyen JDK, Yohannes KG, Setiady I, et al (2025)

Factors associated with failure of fecal microbiota transplant for recurrent Clostridioides difficile infection.

Therapeutic advances in gastroenterology, 18:17562848251334517.

BACKGROUND: Clostridioides difficile infection (CDI) has emerged as a prevalent and recurrent antibiotic-associated infection. Fecal microbiota transplantation (FMT) is the most effective treatment for recurrent CDI (rCDI). Despite high success rates, FMT is ineffective in 5%-20% of cases. Factors associated with failure have not been clearly defined.

OBJECTIVES: In this study, we seek to identify factors predictive of FMT failure.

DESIGN: Retrospective cohort study.

METHODS: A retrospective chart review was conducted on adult patients who were screened at the Complicated C. difficile Clinic at the University of Virginia Health System and received FMT for rCDI between 2013 and 2022. The primary outcome was failure of FMT, defined as either rCDI or all-cause death within 1 year.

RESULTS: In total, 240 patients underwent FMT: 70.4% were female, the median age was 68, and the median episode of CDI was 4. A total of 24.6% experienced failure within 1 year (18.3% had rCDI and 7.1% died). Age 70 or older (odds ratio (OR) = 2.66 (1.29-5.67)), ⩾4 episodes of CDI (OR = 3.13 (1.47-7.09)), and diabetes mellitus (OR = 2.82 (1.25-6.50)) were associated with failure on multivariate analysis.

CONCLUSION: Our study shows that FMT remains an effective treatment for rCDI. We highlight several factors associated with FMT failure, such as older age, ⩾4 episodes of CDI, and diabetes mellitus, and the need for additional research to clearly define causality.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Zheng H, Chen Y, Lu S, et al (2025)

Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.

Gut microbes, 17(1):2497399.

The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.

RevDate: 2025-04-28
CmpDate: 2025-04-29

Ahmadi A, Shokoohizadeh L, Sheikhesmaili F, et al (2025)

Gut microbiomes and treatment-resistant ulcerative colitis: a case-control study using qPCR.

BMC microbiology, 25(1):254.

BACKGROUND: The gut microbiome has been identified as a pivotal factor in ulcerative colitis (UC), given its role as the main reservoir of microbes in the body. This community of microorganisms, present in variable concentrations in the digestive tract, makes a wide range of beneficial roles for the host. However, the role of the gut microbiome in patients with refractory UC is still significant, so this study aimed to further investigate the role of these bacteria in patients with refractory UC.

METHODS: This case-control study was conducted on stool samples from four distinct groups: the first group comprised new patients diagnosed with ulcerative colitis (all of them had responded to treatment after follow-up) (N = 24); the second group consisted of patients with treatment-resistant ulcerative colitis (N = 23); the third group included first-degree relatives of group 1 patients (N = 24); and the fourth group consisted of first-degree relatives of group 2 patients (N = 23). The research tools employed in this study included a questionnaire, quantitative real-time PCR (qPCR) test, and culture on stool samples.

RESULT: The mean age of patients in groups 1 and 2 was 45.88 ± 18.51 and 41.30 ± 13.01 years, while the mean age of controls in groups 3 and 4 was 37.29 ± 9.62 and 40.96 ± 13.01 years, respectively. Stool culture results for pathogenic bacteria were negative in all four groups. The of history of consuming dairy products containing probiotics was highest in Group 1, with 22 (91.67%) subjects, while the lowest was observed in Group 3, with 16 (66.67%). The highest history of self-administered antibiotic use was observed in Group 2, with 13 cases (56.52%), while the lowest was noted in Group 3, with 4 cases (16.67%). The findings indicated a statistically significant relationship (P < 0.05) between Groups 2 and 4 with respect to the E. coli and Bifidobacterium ssp. microbial population. Additionally, a significant relationship was identified between the Lactobacillus ssp., Bifidobacterium ssp., and Bacteroides ssp. microbial community between groups 1 and 2 (P < 0.05).

CONCLUSION: The findings of this study demonstrated that several intestinal microbiomes have a substantial impact on the management of ulcerative colitis. The results of this study suggest that by comparing the gut microbiome of treatment-resistant and individuals newly diagnosed with ulcerative colitis, we can gain a better understanding of microbiome differences that may influence treatment outcomes. The results of this study may also lead to the identification of new therapeutic strategies that are based on regulating the gut microbiome. These strategies could include the use of fecal microbiome transplantation (FMT), probiotics, prebiotics, or specific bacteria-based therapies.

RevDate: 2025-04-30
CmpDate: 2025-04-29

Mohammadi M, Rahimi K, Rezaie A, et al (2025)

The role of fecal microbiota transplantation on the NLRP3-Caspase 1 pathway and anxiety like behavioral in the ulcerative colitis model in rats.

Scientific reports, 15(1):14831.

The purpose of this study was to investigate the function of the NLRP3-Caspase 1 signaling pathway in the colon during fecal microbiota transplantation (FMT) in colitis induced by acetic acid. Additionally, the study aimed to determine the impact of FMT on anxiety behaviors by analyzing the function of the NLRP3-Caspase 1 signaling pathway in the hippocampus. A total of twenty-four rats were selected randomly for the study and divided into two groups, a control group, and an acid acetic-induced colitis group. The acid acetic-induced colitis group further consisted of three subgroups: untreated acid acetic-induced colitis group, mesalazine 0.3 gr/kg group, and FMT group. After 6 days, the colon was evaluated for macroscopic and microscopic damage, and the signaling pathway NLRP3-Caspase1-related genes in the colon and hippocampus were analyzed. Additionally, anxiety-related behaviors of the rats were observed. FMT decreased colonic mRNA expression levels of NLRP3, NF-кB, and Caspase1 and pro-inflammatory cytokines (IL-1β and IL-18). Also, FMT reduced the expression of NLRP3, NF-κB, and Caspase1 protein levels as well as pro-inflammatory cytokines IL-1β and IL-18 in the hippocampus, resulting in a reduction of anxiety behaviors in the open field and elevated plus maze tests in the colitis model. FMT may improve acetic acid-induced colitis by regulating the NLRP3-Caspase1 signaling pathway in the colon. It also reduced colitis-induced anxiety behavior by regulating the expression of proteins related to the NLRP3-Caspase 1 pathway in the hippocampus.

RevDate: 2025-04-28
CmpDate: 2025-04-29

Sun J, Shi L, Xu F, et al (2025)

Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway.

Journal of microbiology and biotechnology, 35:e2412029 pii:jmb.2412.12029.

Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.

RevDate: 2025-04-28

Duarte L, Magne F, M Gotteland (2025)

Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease.

Current opinion in clinical nutrition and metabolic care [Epub ahead of print].

PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.

RECENT FINDINGS: Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.

SUMMARY: Levels of harmful bacterial metabolites including ethanol, NH3, trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.

RevDate: 2025-04-29
CmpDate: 2025-04-28

Ma P, Wang R, Chen H, et al (2025)

Fecal microbiota transplantation alleviates lipopolysaccharide-induced osteoporosis by modulating gut microbiota and long non-coding RNA TUG1 expression.

Frontiers in cellular and infection microbiology, 15:1535666.

PURPOSE: To study whether fecal microbiota transplantation (FMT) can alleviate lipopolysaccharide (LPS)-induced osteoporosis (OP) by regulating the composition and abundance of gut microbiota and the expression level of long non-coding RNA (lncRNA) TUG1.

METHODS: Twenty C57BL/6 mice were selected. Two mice were randomly designated as fecal donors, while the remaining mice were randomly divided into control group, LPS group, and LPS + FMT group. Each group consisted of 6 mice. The mice in the LPS and LPS + FMT groups were intraperitoneally injected with LPS to establish the OP model, and the mice in the LPS + FMT group were treated with donor feces by gavage. Micro-CT was used to scan the femur specimens of mice, and the bone structural parameters of the control and LPS groups were compared to verify the effectiveness of the OP model. HE staining was used to compare the microstructure of femurs in the 3 groups. 16S rRNA gene sequencing was used to analyze the composition and abundance of gut microbiota in mice. Immunofluorescence staining was used to compare the expression levels of Runt-related transcription factor 2 (RUNX2) in the femur of the 3 groups. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to compare the expression levels of lncRNA TUG1 in the intestines and serum of mice in the 3 groups.

RESULTS: Micro-CT showed that compared with the control group, the mice in the LPS group had more bone loss. The bone mineral density, trabecular number, and trabecular thickness of the control group was higher, and the trabecular separation was smaller. The models were validated effectively. HE staining showed that compared with the control group, the bone trabeculae in the LPS group were thinner and sparse, while that in the LPS + FMT group were dense and clear. The 16s rRNA sequencing showed that the abundance of Bacteroides and Lactobacillus in LPS+FMT group was significantly higher than that in LPS group. Immunofluorescence staining showed that the RUNX2 level in the control group and LPS + FMT group was similar, and both were higher than that in the LPS group. The qRT-PCR results showed that the TUG1 mRNA level in the control group and LPS + FMT group was similar and significantly higher than that in the LPS group.

CONCLUSION: FMT can enhance osteoblast levels and improve bone structure by modulating the abundance of gut microbiota in OP mice (such as increasing Bacteroides and Lactobacillus populations) and promoting the expression of lncRNA TUG1, thereby alleviating LPS-induced OP.

RevDate: 2025-04-29
CmpDate: 2025-04-28

Bu F, Chen K, Chen S, et al (2025)

Gut microbiota and intestinal immunity interaction in ulcerative colitis and its application in treatment.

Frontiers in cellular and infection microbiology, 15:1565082.

Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease characterized by inflammation and injury of the colonic mucosa, exhibiting an increasing global incidence. Although research into UC pathogenesis is ongoing, the precise mechanisms remain to be fully elucidated. Studies indicate that UC development results from a complex interplay of factors, including genetic predisposition, environmental exposures, gut microbial dysbiosis, and immune dysregulation. Specifically, UC pathogenesis involves aberrant immune responses triggered by interactions between the host and gut microbiota. A complex, dynamic relationship exists between the microbial community and the host immune system throughout UC pathogenesis. Accumulating evidence suggests that changes in microbiota composition significantly impact gut immunity. This review will examine the intricate balance between the gut microbiota and mucosal immunity in UC progression and discuss potential therapeutic applications, providing a reference for further clinical treatment of this patient population.

RevDate: 2025-04-29
CmpDate: 2025-04-28

Mattar L, Thalib HI, Alnuwaimi M, et al (2025)

Challenges of concurrent HIV infection in the course and management of Crohn's disease.

Journal of medicine and life, 18(3):171-178.

Crohn's disease (CD) is a chronic transmural bowel inflammation with a multifactorial etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. In patients with human immunodeficiency virus (HIV), an already compromised immune system further complicates the progression and management of CD, creating unique therapeutic challenges. Probiotics have recently gained attention as a potential therapeutic option for CD, especially due to their role in modulating the gut microbiota. However, their effectiveness in patients with HIV, especially in enhancing and maintaining remissions, remains underexplored. This review aimed to examine how HIV infection influences the course of inflammatory bowel disease (IBD) and its impact on CD management strategies. A systematic literature search was conducted using Google Scholar, PubMed, Springer, and Web of Science to identify studies on patients with HIV and CD. HIV infection significantly alters the progression and management of CD due to its impact on the immune system. The immunosuppressed state of patients with HIV can complicate both the diagnosis and treatment of CD, often requiring adjustments in therapeutic approaches, necessitating a careful, tailored approach.

RevDate: 2025-04-28

Gao L, Zhang Y, Hu Z, et al (2025)

Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus-like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the eDDxtracellular signal-regulated kinase (ERK)-hypoxia-inducible factor-1alpha (HIF-1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.

RevDate: 2025-04-28

Xu Z, Li L, Cheng L, et al (2025)

Maternal obesity and offspring metabolism: revisiting dietary interventions.

Food & function [Epub ahead of print].

Maternal obesity increases the risk of metabolic disorders in offspring. Understanding the mechanisms underlying the transgenerational transmission of metabolic diseases is important for the metabolic health of future generations. More research is needed to elucidate the mechanisms underlying the associated risks and their clinical implications because of the inherently complex nature of transgenerational metabolic disease transmission. Diet is a well-recognized risk factor for the development of obesity and other metabolic diseases, and rational dietary interventions are potential therapeutic strategies for their prevention. Despite extensive research on the physiological effects of diet on health and its associated mechanisms, little work has been devoted to understanding the effects of early-life dietary interventions on the metabolic health of offspring. In addition, existing dietary interventions are insufficient to meet clinical needs. Here, we discuss the literature on the effects of maternal obesity on the metabolic health of offspring, focusing on the mechanisms underlying the transgenerational transmission of metabolic diseases. We revisit current dietary interventions and describe their strengths and weaknesses in ameliorating maternal obesity-induced metabolism-related disorders in offspring. We also propose innovative strategies, such as the use of precision nutrition and fecal microbiota transplantation, which may limit the vicious cycle of intergenerational metabolic disease transmission.

RevDate: 2025-04-28
CmpDate: 2025-04-28

Grimstad T, Carlsen A, Kvaløy JT, et al (2025)

Fatigue in Inflammatory Bowel Disease: No Effect of Serum Concentrations of Infliximab, Adalimumab or Anti-Drug Antibodies During Maintenance Therapy.

Scandinavian journal of immunology, 101(5):e70029.

Several studies have shown that infliximab and adalimumab ameliorate fatigue in inflammatory bowel disease. We investigated whether serum levels of these agents above or below a selected threshold influence fatigue severity. In this cross-sectional study, we measured serum concentrations (s-) of infliximab and adalimumab and corresponding anti-drug antibody levels. Therapeutic thresholds were defined as s-infliximab ≥ 5.0 mg/L and s-adalimumab ≥ 7.0 mg/L. Disease activity was assessed using the Harvey-Bradshaw Index for Crohn's disease, Partial Mayo Score for ulcerative colitis, and C-reactive protein (CRP) and faecal calprotectin levels for both conditions. Fatigue was assessed with the Fatigue Visual Analog Scale and Fatigue Severity Scale, and depression was evaluated with the Hospital Anxiety and Depression Scale, Depression subscale. Of 171 included patients (112 with Crohn's disease, 59 with ulcerative colitis), 66 (38.6%) were on infliximab and 105 (61.4%) were on adalimumab. Scores on the two fatigue scales were similar for serum values above versus below therapeutic thresholds for both drugs and did not differ with versus without anti-drug antibodies against either drug. CRP was numerically higher with infliximab levels below versus above the threshold (p = 0.06), whereas both CRP and faecal calprotectin were increased with adalimumab below versus above the threshold (p = 0.022, p = 0.0242). In patients with inflammatory bowel disease on maintenance therapy, s-infliximab and s-adalimumab levels below or above therapeutic thresholds or the presence of anti-drug antibodies did not affect fatigue severity. Trial Registration: ClinicalTrials.gov identifier: NCT02134054.

RevDate: 2025-04-27

La Rosa F, Guzzardi MA, Pardo-Tendero M, et al (2025)

Effects of Children's Microbiota on Adipose and Intestinal Development in Sex-Matched Mice Persist into Adulthood Following a Single Fecal Microbiota Transplantation.

Molecular metabolism pii:S2212-8778(25)00064-X [Epub ahead of print].

BACKGROUND: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood.

OBJECTIVE: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life.

METHODS: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics.

RESULTS: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet.

CONCLUSION: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.

RevDate: 2025-04-27

Banerjee A, Mal S, Roy P, et al (2025)

Regulating environmental arsenic-mediated gut-brain toxicity using chitosan-conjugated luteolin gold nanoparticles.

Ecotoxicology and environmental safety, 297:118250 pii:S0147-6513(25)00586-X [Epub ahead of print].

Anxiety and depression are two major contributors to global disease burden. Amongst various causal factors, exposure to even low doses of environmental heavy metals, like arsenic, can induce anxiety and depression-like behaviour in mammals. Ingestion of arsenic, primarily through contaminated drinking water, severely disrupts the gut microbes, thereby inducing structural and functional abnormalities in the brain. Fecal microbiota transplantation (FMT) from arsenic-exposed mice to recipient healthy mice (As-FMT) enriched LPS-secreting Gram-negative bacteria and upregulated the expression of TLR4 in intestinal epithelial cells. Consequently, inflammation, oxidative stress and compromised barrier integrity in the gut facilitated LPS translocation into the bloodstream and promoted systemic inflammation. The secretomes eventually affected the brain by activating microglia, altering neurotransmitter levels and reducing the glucocorticoid receptor (GR) expression, contributing to appearance of pyknotic nuclei in dentate gyrus of hippocampus and emergence of anxiety- and depression-like behaviour. Luteolin, a flavonoid, devoid of any apparent side-effects, yet known for its anti-inflammatory and antioxidant properties, showed potential in alleviating the gut-brain toxic effects. However, its limited solubility and bioavailability pose challenges for its effectiveness, for which chitosan-conjugated luteolin gold nanoparticles (CH-LuAuNPs) were synthesized. Interestingly, where FMT from arsenic-treated mice to healthy mice showed deleterious effects in the transplanted mice, FMT from arsenic-treated mice co-administered with CH-LuAuNP attenuated As-FMT-mediated disruption of the gut-brain axis. This study highlighted the critical contribution of healthy gut microbiota in preserving neurobehavioural physiology, as well as underscored the potential therapeutic benefits of luteolin nanoparticles in ameliorating arsenic-induced gut dysbiosis and consequent mental disorders.

RevDate: 2025-04-29
CmpDate: 2025-04-27

Zou T, Tang X, Wang H, et al (2025)

Nanocrystalline cellulose-geniposide complex enhances gut-brain axis modulation for depression treatment.

Communications biology, 8(1):667.

Depression, a major global health issue, is closely associated with imbalances in gut microbiota and altered intestinal functions. This study investigates the antidepressant potential of a composite of Geniposide (GP) and Nanocrystalline Cellulose (NCC), focusing on its effects on the gut-brain axis. Utilizing network pharmacology, GP was identified as a key compound targeting the BCL2 gene in depression management. Experimental approaches, including a chronic unpredictable mild stress (CUMS) model in mice, cellular assays, and fecal microbiota transplantation (FMT), were used to evaluate the composite's effectiveness. Results indicate that GP activates the adenosine monophosphate-activated protein kinase (AMPK) pathway by upregulating BCL2, enhancing intestinal barrier integrity, and balancing gut flora. These mechanisms contribute to its positive effects on hippocampal function and depressive-like behaviors in mice, suggesting that the GP-NCC composite could be a promising avenue for developing depression therapies that target gut health.

RevDate: 2025-04-26

Ji H, Dong Z, Yang Y, et al (2025)

Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 142:156775 pii:S0944-7113(25)00414-3 [Epub ahead of print].

BACKGROUND: Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.

METHODS: We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.

RESULT: Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients'serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.

CONCLUSION: NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota-a significant advance in the prevention and treatment of CAs.

RevDate: 2025-04-26

Hansen SH, Maseng MG, Grännö O, et al (2025)

Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort.

Inflammatory bowel diseases pii:8120328 [Epub ahead of print].

INTRODUCTION: We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD).

METHODS: Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling.

RESULTS: A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001).

CONCLUSIONS: Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.

RevDate: 2025-04-28

Zhang Y, Wang L, L Peng (2025)

The Role of Intestinal Fungi in the Pathogenesis and Treatment of Ulcerative Colitis.

Microorganisms, 13(4):.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.

RevDate: 2025-04-28
CmpDate: 2025-04-26

Bonomo MG, D'Angelo S, Picerno V, et al (2025)

Recent Advances in Gut Microbiota in Psoriatic Arthritis.

Nutrients, 17(8):.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.

RevDate: 2025-04-28

Boicean A, Ichim C, Sasu SM, et al (2025)

Key Insights into Gut Alterations in Metabolic Syndrome.

Journal of clinical medicine, 14(8):.

Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.

RevDate: 2025-04-28

Marano G, Rossi S, Sfratta G, et al (2025)

Gut Microbiota: A New Challenge in Mood Disorder Research.

Life (Basel, Switzerland), 15(4):.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.

RevDate: 2025-04-26

Nemati MH, Yazdanpanah E, Kazemi R, et al (2025)

Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential.

Biology, 14(4):.

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.

RevDate: 2025-04-26

Dipasquale V, C Romano (2025)

New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.

Healthcare (Basel, Switzerland), 13(8):.

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

RevDate: 2025-04-28
CmpDate: 2025-04-26

Wissel EF, Chien HY, Wei KH, et al (2025)

Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis.

Scientific reports, 15(1):14576.

Heart Failure (HF) impacts approximately 64 million people globally. While overall incidence of HF is relatively stable across countries, the overall number of HF patients is increasing due to aging populations. Many articles examine the microbiome in HF, however, studies from humans have not been analyzed systematically. The aim of this meta-analysis is to bridge this gap by analyzing previously published data on human HF patients with untargeted metabolomics to understand whether microbially-mediated metabolites are consistently important for HF status. A systematic survey of the literature identified 708 articles discussing HF, the microbiome, and metabolomics. Of these, 82 were primary studies of HF patients, 61 studied human adults, 23 included an untargeted metabolomics measure, and 3 studies had data that was usable and publicly accessible. These studies include a GCMS study from stool, NMR of saliva and exhaled breath condensate, and LCMS from left ventricle of HF patients undergoing transplantation and unused donor hearts. Significant differences were observed from PCA between HF and controls for stool and left ventricle, but not saliva or EBC samples. OPLS-DA was conducted for stool and ventricle samples, and further revealed significant group differences. Univariate testing with FDR correction revealed 8 significant microbially-relevant metabolites (p < 0.005 after correction), most notably asparagine from left ventricle and 2-methylbutyryl carnitine from stool. Though there is much discussion of the microbiome in health outcomes in HF, there is limited research from human populations. Some microbial co-metabolites from both stool and heart were significantly associated with HF.

RevDate: 2025-04-25

Wellens J, Vissers E, Dumoulin A, et al (2025)

Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.

Cell reports. Medicine pii:S2666-3791(25)00164-8 [Epub ahead of print].

Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis. We show that low-AGE-generating cooking methods such as boiling and steaming decrease serum AGEs, improve lipid profiles, and increase serum protein 4E-BP1. In contrast, high-AGE-generating cooking methods such as grilling and baking increase fecal butyrate. In sum, this suggests that low-AGE-generating cooking methods should be considered in cardiovascular risk prevention. Since current dietary guidelines focus on ingredients, but not cooking methods, our results suggest that culinary techniques should be considered as an important factor in cardiometabolic preventive strategies and future dietary trial design. This study was registered at ClinicalTrials.gov (NCT06547190).

RevDate: 2025-04-25

Cai W, Haddad M, Haddad R, et al (2025)

The gut microbiota promotes pain in fibromyalgia.

Neuron pii:S0896-6273(25)00252-1 [Epub ahead of print].

Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.

RevDate: 2025-04-25

Zheng Z, Du Y, Jiang H, et al (2025)

KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 142:156766 pii:S0944-7113(25)00405-2 [Epub ahead of print].

BACKGROUND: Colorectal cancer liver metastasis (CRLM) represents one of the most severe complications of colorectal cancer (CRC), often associated with unfavorable prognosis. The herbal formulation Kang-Ai-Jing-Fang (KAJF) has been employed clinically against CRC for several decades, although its precise mechanism of action remains elusive.

PURPOSE: This study investigates the anti-metastatic potential of KAJF in CRLM, focusing on its modulatory effects on gut microbiota and inhibition of M2-like macrophage activation.

METHODS: KAJF was administered orally to CRLM model mice established through intrasplenic injection of murine CRC cells. To elucidate the role of gut microbiota reshaped by KAJF, fecal microbiota transplantation (FMT) was utilized to assess its impact on CRLM inhibition. Core targets and active compounds were identified through network pharmacology and molecular docking. To characterize microbiota composition, metabolite profiles, and gene expression variations, 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, and transcriptomics analyses were performed.

RESULTS: KAJF demonstrated significant inhibitory effects on CRLM and ameliorated gut microbiota dysbiosis by enhancing the abundance of butyrate-producing bacteria (Lactobacillus, Bacteroides, Bifidobacterium). The therapeutic efficacy of KAJF-induced bacterial alterations in delaying CRLM and promoting butyrate-producing microbiota enrichment was further substantiated by FMT. Network pharmacology identified active ingredients in KAJF, including asperulosidic acid, polyphyllin II, ganoderenic acid B, calycosin, and ganoderic acid C, which exhibit substantial interactions with TLR4, PPARγ, SIRT1, PTGS2, and TNF. Molecular dynamics simulations and surface plasmon resonance (SPR) analysis demonstrated that ganoderic acid C2 exhibits a strong binding affinity for PPARγ. Moreover, KAJF administration led to a marked reduction in F4/80[+] CD206[+] macrophages and their associated cytokines (CCL17, CCL22, IL10, IL4, TGF), accompanied by a decrease in CD4[+] T cells and myeloid-derived suppressor cells (MDSCs), while increasing CD8[+] T cell populations.

CONCLUSIONS: This study demonstrates that KAJF mitigates CRLM, primarily through the regulation of gut microbiota and microbial metabolites, alongside inhibition of M2-like macrophage polarization. By integrating metabolomics, transcriptomics, and network pharmacology, this research elucidates the molecular mechanisms underpinning KAJF's therapeutic effects against CRLM, offering a promising approach for clinical intervention.

RevDate: 2025-04-25

Zhang S, Qian Y, Li N, et al (2025)

Specific MSI2 deletion maintains intestinal barrier integrity by down-regulating ILC3s-derived IL-17 a in mice with colitis.

International immunopharmacology, 156:114717 pii:S1567-5769(25)00707-6 [Epub ahead of print].

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with an unknown cause. Previous studies have shown that Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining intestinal mucosal immune homeostasis by producing key cytokines such as IL-22 and IL-17 A. While the RNA-binding protein Musashi-2 (MSI2) is recognized as essential for promoting intestinal epithelial regeneration post-injury, its impact on immune regulation remains unclear. Therefore, we aim to investigate the protective mechanisms associated with ILC3s-specific MSI2 deletion in a mouse model of ulcerative colitis.

METHODS: Dextran sulfate sodium (DSS) was used to induce a mouse colitis model. Colitis severity was evaluated through weight loss, diarrhea, fecal traits, colon length, and pathological scoring. Transcriptome sequencing was utilized to identify differentially expressed genes in colon tissues. Flow cytometry was employed to measure the quantity and functionality of ILC3s. Western blot was conducted to analyze protein expression, while real-time polymerase chain reaction and enzyme-linked immunosorbent assay were employed to quantify inflammatory factors. Additionally, immunofluorescence, AB-PAS staining, and immunohistochemistry were employed to evaluate the integrity of the intestinal barrier.

RESULTS: Following DSS treatment, colon damage was milder in Msi2[∆Rorc] mice than in Msi2[fl/fl] mice. Transcriptomic analysis revealed the down-regulation of cytokines and pro-inflammatory factors in the colon tissue of Msi2[∆Rorc] mice. Flow cytometry showed that specific deletion of MSI2 reduced the infiltration of ILC3s in the intestinal lamina propria of Msi2[∆Rorc] mice and decreased IL-17 A production. The reduction of IL-17 A-mediated immune responses lessened inflammatory damage to the intestinal barrier, thereby reducing colitis severity.

CONCLUSIONS: Specific deletion of MSI2 alleviates DSS-induced colitis in mice by reducing ILC3s infiltration and IL-17 A secretion in the lamina propria of the colon. This decrease in inflammatory mediators and cell infiltration dampens the inflammatory response in the intestinal mucosa, helping to maintain the integrity of the intestinal barrier in mice with colitis. These findings enhance our understanding of UC pathogenesis and offer novel avenues for clinical diagnosis and treatment.

RevDate: 2025-04-27

Zheng F, Yang Y, Lu G, et al (2025)

Metabolomics Insights into Gut Microbiota and Functional Constipation.

Metabolites, 15(4):.

Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites-such as SCFAs, bile acids, neurotransmitters, and microbial gases-play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism-with decreased secondary bile acids like deoxycholic acid-disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.

RevDate: 2025-04-24

Ji ZH, Xie WY, Wu HY, et al (2025)

Coix Seed Polysaccharide Mitigates Ulcerative Colitis in Mice through the Modulation of Gut Microbiota and Improvement of Intestinal Metabolism Balance.

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

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising incidence globally, whereas existing treatments exhibit significant limitations. Coix seed polysaccharide (CSP), a component of traditional Chinese medicine known for its immunomodulatory and antioxidant properties, has not been thoroughly investigated for its role in UC. In this study, CSP was prepared via water extraction and ethanol precipitation, and its protective effects and mechanisms were evaluated using a dextran sulfate sodium salt (DSS)-induced UC mouse model. The results demonstrated that CSP significantly ameliorated DSS-induced UC symptoms, including weight loss, an elevated Disease Activity Index, colon shortening, increased levels of inflammatory cytokines, and intestinal barrier damage. Moreover, CSP reshaped the DSS-induced gut microbiota dysbiosis by increasing gut microbial diversity and regulating the abundance of specific genera, such as increasing Anaerotruncus. Metabolomic analysis revealed that CSP significantly modulated the levels of 116 metabolites, particularly enhancing the beneficial metabolite 3-hydroxybutyrate. Importantly, the preventive effect of CSP on UC was dependent on the gut microbiota and could be transferred via fecal microbiota transplantation. This study demonstrates that CSP, a microecology-regulating polysaccharide, effectively modulates gut microbiota and alleviates symptoms of UC. These findings support the potential of CSP as a dietary supplement for UC prevention and underscore its value in the development of medicinal foods and functional food applications.

RevDate: 2025-04-24

Chang Z, Zhu Y, Wang P, et al (2025)

Multi-omic analyses of the development of obesity-related depression linked to the gut microbe Anaerotruncus colihominis and its metabolite glutamate.

Science bulletin pii:S2095-9273(25)00359-7 [Epub ahead of print].

Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.

RevDate: 2025-04-24

Bohm MS, Joseph SC, Sipe LM, et al (2025)

The gut microbiome enhances breast cancer immunotherapy following bariatric surgery.

JCI insight pii:187683 [Epub ahead of print].

Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant (FMT). Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric surgery-treated mice. When stool from post-bariatric surgery patients was transplanted into recipient mice and compared to the patients' pre-surgery transplants, post-surgery microbes significantly reduced tumor burden and doubled immunotherapy effectiveness. Microbes impact tumor burden through microbially derived metabolites, including branched chain amino acids (BCAA). Circulating BCAAs correlated significantly with natural killer T (NKT) cell content in the tumor microenvironment in donor mice after bariatric surgery and FMT recipients of donor cecal content after bariatric surgery compared to obese controls. BCAA supplementation replicated improved αPD-1 effectiveness in two BC models, supporting the role of BCAAs in increased immunotherapy effectiveness after bariatric surgery. Ex vivo exposure increased primary NKT cell expression of anti-tumor cytokines, demonstrating direct activation of NKT cells by BCAAs. Together, findings suggest that reinvigorating anti-tumor immunity may depend upon bariatric surgery-associated microbially derived metabolites, namely BCAAs.

RevDate: 2025-04-26
CmpDate: 2025-04-24

Ubsdell D, Maddox NL, R Sheridan (2025)

Management of severe and fulminant Clostridioides difficile infection in adults.

Journal of medical microbiology, 74(4):.

Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.

RevDate: 2025-04-24

Dai X, Cao Y, Li L, et al (2025)

Gut microbiome and metabolome profiles in renal allograft rejection from multiomics integration.

mSystems [Epub ahead of print].

UNLABELLED: The gut microbiome and metabolome play crucial roles in renal allograft rejection progression. Integrated multiomics analyses may provide a comprehensive understanding of specific underlying mechanisms, which remain elusive. This study aimed to identify new approaches for clinical renal allograft rejection diagnosis and treatment. Thirty-five patients were divided into three groups: the rejection (n = 16), dysfunction (n = 7), and control (n = 12) groups. Metagenomic sequencing and nontargeted metabolomics were used to analyze stool and plasma samples. Significant microbiota, metabolites, and signaling pathways were identified. LASSO regression was used to construct a diagnostic model, and its diagnostic value was assessed via receiver operating characteristic curves. The microbiota composition and the related genes in the rejection group significantly differed from that in the dysfunction and control groups at the phylum, genus, and species levels (P < 0.001). The core species in the rejection group networks were Escherichia coli and Ruminococcus gnavus, while core species in the dysfunction group networks were Faecalibacterium prausnitzii and Bacteroides ovatus. The balance of specific microbial species was associated with kidney function in rejection patients. Spearman analysis revealed that specific differential species like Agathobaculum butyriciproducens and Gemmiger qucibialis were closely linked to the levels of serum 4-pyridoxic acid, 4-acetamidobutanoate, and fecal tryptamine from specific differential pathways. Finally, we constructed four clinical models to distinguish the rejection and dysfunction groups, and the model had excellent diagnostic performance. Altered gut microbiota may contribute to changes in metabolic pathway activity and metabolite abundance in rejection and dysfunction patients, which are strongly correlated with host immunological rejection. The diagnostic model, developed based on the gut microbiota and metabolites, has high clinical value for diagnosing renal rejection.

IMPORTANCE: This study aimed to screen new markers for non-invasive diagnosis by the gut microbiome and metabolome analysis, providing new insights into rejection mechanisms and identifying new approaches for clinical renal allograft rejection diagnosis.

RevDate: 2025-04-24

Schoultz I, Claesson MJ, Dominguez-Bello MG, et al (2025)

Gut microbiota development across the lifespan: Disease links and health-promoting interventions.

Journal of internal medicine [Epub ahead of print].

The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.

RevDate: 2025-04-23
CmpDate: 2025-04-23

Zhang D, Zhang Z, Liao L, et al (2025)

Impact of fecal microbiota transplantation on lung function and gut microbiome in an ARDS rat model: A multi-omics analysis including 16S rRNA sequencing, metabolomics, and transcriptomics.

International journal of immunopathology and pharmacology, 39:3946320251333982.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a severe pulmonary condition characterized by inflammation and lung damage, frequently resulting in poor clinical outcomes. Recent studies suggest that the gut-lung axis, mediated by gut microbiota, is critical in ARDS progression. This study investigates the therapeutic potential of fecal microbiota transplantation (FMT) in an ARDS rat model (n = 6).

INTRODUCTION: The pathogenesis of ARDS involves complex interactions between the lungs and gut, with microbiota playing a key role. Understanding the effects of FMT on lung function and gut microbiota may provide new therapeutic strategies for ARDS management.

METHODS: Sprague-Dawley rats were pre-treated with a broad-spectrum antibiotic cocktail to create a germ-free state and subsequently exposed to intranasal lipopolysaccharide to induce ARDS. The rats then received FMT treatment. Lung samples were analyzed using histopathology and transcriptomics. Fecal samples were analyzed using 16S rRNA sequencing and metabolomics.

RESULTS: FMT treatment significantly reduced lung injury and improved pulmonary function, as evidenced by increased partial pressure of arterial oxygen (PaO2) and decreased partial pressure of arterial carbon dioxide (PaCO2). FMT also significantly altered in gut microbiota composition by regulating the gut microbiota composition of Akkermansia and Lactobacillus, restoring the abundance of genera such as Muribaculaceae, Clostridia_UCG-014, Prevotella, and Adlercreutzia, while reducing Romboutsia. FMT restored key metabolic pathways involved in lipid metabolism, amino acid biosynthesis, and immune regulation, including the modulation of immune pathways like mTOR signaling. These alterations contribute to reduced lung injury and improved pulmonary function.

CONCLUSION: These findings indicate that FMT may exert its beneficial effects in ARDS by modulating the gut microbiota and enhancing metabolic and immune responses. However, given that this study remains in the preclinical stage, further validation in clinical studies is necessary before considering clinical application.

RevDate: 2025-04-23
CmpDate: 2025-04-23

He G, Zhang B, Chen T, et al (2025)

Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis.

Food research international (Ottawa, Ont.), 208:116218.

Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.

RevDate: 2025-04-25
CmpDate: 2025-04-23

Kumpunya S, Kawang K, Pollapong K, et al (2025)

The effects of repeated fecal transplantation and activated charcoal treatment on gut dysbiosis induced by concurrent ceftriaxone administration in mice.

Scientific reports, 15(1):13908.

BACKGROUND: Antibiotic treatment contributes to gut microbiota dysbiosis. Previous studies have shown that fecal microbiota transplantation (FMT), fecal filtrate (FF), and activated charcoal (AC) treatments can prevent gut microbiota disturbances caused by antibiotics or Clostridioides difficile infection. However, these treatments have typically been limited to restoring gut microbiota after dysbiosis, and antibiotics must be discontinued beforehand. Here, we investigated the protective effects of these treatments on gut microbiota to prevent dysbiosis during concurrent systemic ceftriaxone administration.

METHODS: C57BL/6 mice that received intraperitoneal ceftriaxone for seven consecutive days were concomitantly treated with AC, FMT, FMT + AC, FF, or FF + AC via oral gavage. Gut microbiomes were analyzed using 16 S rRNA gene sequencing, and intestinal mucosal pathology was evaluated through H&E staining.

RESULTS: Systemic ceftriaxone administration significantly altered gut microbiota diversity and composition but did not affect intestinal mucosal histology. Alpha and beta diversity analyses showed that microbiota diversity decreased in all ceftriaxone-treated groups, with the ceftriaxone + FF + AC group retaining the highest diversity. The ceftriaxone + AC group had higher Enterococcus but lower Muribaculaceae relative abundances than the control (no ceftriaxone), ceftriaxone only, and ceftriaxone + FF + AC groups.

CONCLUSIONS: These results show that fecal filtrate transplantation combined with activated charcoal treatment may help balance gut microbiota diversity and reduce the presence of resistant bacteria during ceftriaxone exposure.

RevDate: 2025-04-25
CmpDate: 2025-04-23

Chi Q, Tang J, Ji C, et al (2025)

Profiling electric signals of electrogenic probiotic bacteria using self-attention analysis.

Applied microbiology and biotechnology, 109(1):100.

We fabricated a self-assembled electric circuit to detect the electrical signals produced by two electrogenic probiotic bacteria [Leuconostoc mesenteroides (L. mesenteroides) and Lactococcus lactis (L. lactis)] on chicken egg chorioallantoic membranes as well as in the intestine lumen of mice. Inoculation of L. mesenteroides or L. lactis plus glucose onto a ferrozine assay triggered the reduction of ferric ions to ferrous ions and the formation of ferrozine complexes, indicating the bacterial electron production. In the presence of glucose, L. lactis yielded higher electricity, measured by voltage changes, than L. mesenteroides in vitro. The spectra of the electrical signals generated by these two probiotic bacteria were highly distinguishable. We evaluated the importance of these differences with the application of a self-attention mechanism, a deep learning-based module, revealing several unique signals in the electrical spectra of L. mesenteroides as well as L. lactis bacteria. The specific electrical spectrum for each probiotic bacterium provided a dynamic signature for evaluation of the efficacy of various therapies using probiotics, antibiotics, and fecal microbiota transplantation in the future. KEY POINTS: • The electrical signals produced by probiotic bacteria L. mesenteroides and L. lactis on chicken egg chorioallantoic membranes and in the mouse intestine lumen were detectable. • In the presence of glucose, L. lactis yielded higher electricity than L. mesenteroides in vitro. Furthermore, the electrical spectra generated by these two bacteria were different. • The importance of these differences with the application of a self-attention mechanism revealed several unique signals in the electrical spectra.

RevDate: 2025-04-22
CmpDate: 2025-04-23

Elkrief A, Routy B, Derosa L, et al (2025)

Gut Microbiota in Immuno-Oncology: A Practical Guide for Medical Oncologists With a Focus on Antibiotics Stewardship.

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 45(3):e472902.

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.

RevDate: 2025-04-22
CmpDate: 2025-04-22

Mahgoup EM (2025)

"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".

Current hypertension reports, 27(1):14.

PURPOSE OF REVIEW: Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.

RECENT FINDINGS: Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.

RevDate: 2025-04-22

Shaukat A, Drekonja DM, Huang Y, et al (2025)

Efficacy and Safety of Fecal Microbiota Transplant for Prevention of Recurrent Clostridioides difficile Infection.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8117311 [Epub ahead of print].

RevDate: 2025-04-22

Davido B, Kharkhordine M, P Moine (2025)

Fecal Microbiota Transplantation in Clostridioides Difficile Infections: Rethinking the Approach by Patient Profile in Light of New Evidence.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8117309 [Epub ahead of print].

RevDate: 2025-04-22

Khoruts A, C Staley (2025)

FMT for Recurrent Clostridioides difficile Infection.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8117303 [Epub ahead of print].

RevDate: 2025-04-22

Paaske SE, Baunwall SMD, Ianiro G, et al (2025)

Clostridioides difficile: Treating Sustained Antibiotic Responders With Fecal Microbiota Transplantation Does Not Improve Efficacy.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8117307 [Epub ahead of print].

RevDate: 2025-04-26
CmpDate: 2025-01-30

Chua HC, Pham S, Lombardi DA, et al (2025)

Patient Satisfaction Scale Following a Laxative for Antibiotic Washout Prior to Oral Microbiome Therapy.

Advances in therapy, 42(1):490-499.

INTRODUCTION: Administration of fecal microbiota spores, live-brpk [Vowst Oral Spores (VOS)], an oral microbiome therapeutic approved for prevention of recurrent Clostridioides difficile infection in adults, requires antibiotic washout using a laxative prior to administration. Patient acceptability of the prerequisite laxative is important. This study assessed psychometric properties of the Antibiotic Washout Patient Satisfaction Scale (AWPSS) which was minimally modified from a previously validated patient satisfaction scale for bowel preparation prior to colonoscopy.

METHODS: Patients from the ECOSPOR IV trial who received a laxative preparation prior to oral administration of VOS and were administered the AWPSS were included. Reliability and construct validity of the AWPSS were evaluated.

RESULTS: AWPSS data were available for 110 patients; all completed all 6 items of the AWPSS, supporting its acceptability. Domain 1 mean/median transformed total scores of 105.9/100 [range (best-worst), 0-300] suggested that patients were satisfied with the laxative preparation; a Cronbach's alpha of 0.81 showed acceptable reliability. Almost all patients (97.3%) reported they were able to consume the entire laxative solution as instructed and would take it again if needed (95.5%). Higher satisfaction with the laxative preparation predicted higher acceptability of future use if needed (lower score) with mean/median of 101.7/100 and 195.0/200.00 for those who were willing or not willing to accept, respectively (P = 0.008).

CONCLUSIONS: AWPSS is a valid and reliable 6-item patient-reported outcome measure for use in patients requiring a laxative prior to oral microbiome therapy. AWPSS showed antibiotic washout was well tolerated and predicted that patients would be willing to consume the laxative in the future if needed.

RevDate: 2025-04-24
CmpDate: 2025-04-21

Cuisiniere T, Hajjar R, Oliero M, et al (2025)

Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model.

Microbiome, 13(1):100.

BACKGROUND: Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in Apc[Min/+] mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.

RESULTS: We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in Apc[Min/+] mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.

CONCLUSIONS: Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.

RevDate: 2025-04-24
CmpDate: 2025-04-21

Kamlárová A, Kvaková M, Ambro Ľ, et al (2025)

Improvement of the inflammation-damaged intestinal barrier and modulation of the gut microbiota in ulcerative colitis after FMT in the SHIME® model.

BMC complementary medicine and therapies, 25(1):145.

BACKGROUND: Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient's dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application.

METHODS: SHIME® model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME® were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier.

RESULTS: Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME® model prevented intestinal barrier damage and inhibited interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24 h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME® model.

CONCLUSIONS: FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME® model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME® model.

RevDate: 2025-04-21

Lund AJ, Metzger ME, Kramer VL, et al (2025)

Low risk for locally acquired Chagas disease in California: A review of human cases and triatomine submissions, 2013-2023.

PLoS neglected tropical diseases, 19(4):e0013036 pii:PNTD-D-25-00273 [Epub ahead of print].

Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is carried in the guts of triatomine insects. Transmission typically occurs when infective trypomastigotes in triatomine feces encounter mucous membranes or bite wounds, though it is also possible by food-borne, transplant- and transfusion-mediated, and congenital routes. Most transmission occurs in rural and peri-urban parts of continental Latin America where triatomines often inhabit human dwellings. Triatomines infected with T. cruzi are also present across the southern United States, yet relatively few locally acquired infections have been documented. Rather, most reported cases have plausible exposure in Latin America. In California, the widespread distribution of T. cruzi-infected triatomines suggests a potential risk of local transmission. Here, we summarize triatomine submissions and human case reports made to the California Department of Public Health between 2013 and 2023. Of 226 triatomines tested, 63 (28%) were positive for T. cruzi via PCR; none were linked to any of the 40 human T. cruzi cases reported in the same period. Human cases were assessed for likelihood of local transmission. Country of birth, travel history, and location of primary residence suggested non-local transmission for 31 (78%) cases. Local transmission could not be ruled out for the remaining nine (22%) cases. Information on country of birth and travel history were missing from these case reports and prevented full assessment of local transmission criteria, though most of these patients resided within 400 meters of potential triatomine habitat. Despite the presence of triatomines, T. cruzi, and human cases in California, statewide data indicates the risk for locally acquired Chagas disease is low.

RevDate: 2025-04-21

Hu M, Zhu X, Huang X, et al (2025)

Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype.

Cell reports, 44(5):115589 pii:S2211-1247(25)00360-2 [Epub ahead of print].

Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome's role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes. Favorable-type enterotypes exhibit higher fungal and bacterial alpha diversity, enriched butyrate-producing bacteria, and metabolic pathways related to butyric acid and sugar/starch metabolism. External validation confirms their predictive value in assessing immunotherapy efficacy. Multi-omics analysis reveals increased CD8[+] T cell infiltration in the tumor microenvironment of favorable-type patients. Fecal microbiota transplantation (FMT) from favorable-type donors enhances anti-PD-1 sensitivity, promotes CD8[+] T cell infiltration, and boosts butyrate production in vivo. These findings highlight the gut mycobiome's role in immunotherapy response and support FMT from favorable-type donors as a potential strategy for improving treatment outcomes and patient stratification.

RevDate: 2025-04-21

Bénard MV, de Bruijn CMA, Matamoros S, et al (2025)

Transient colonization with Blastocystis spp. after transmission via fecal microbiota transplantation.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology [Epub ahead of print].

BACKGROUND: The pathogenicity of Blastocystis spp. is still debated. Guidelines for feces donor screening differ in their advice to screen for Blastocystis spp., but when tested, its presence is a common reason for exclusion. Blastocystis spp. are correlated to increased bacterial alpha-diversity and distinct bacterial groups and therefore its presence may indicate favorable efficacy of fecal microbiota transplantation (FMT). The latest European consensus report no longer advices rejecting feces donors testing positive for Blastocystis spp. Only one paper has been published on human transmission of Blastocystis spp. via frozen FMT.

OBJECTIVE: To investigate the transmission and long-term effects of Blastocystis-positive FMT, prepared with fresh (i.e., unfrozen) feces.

METHODS: In a trial (NCT03074227) on FMT for refractory Irritable Bowel Syndrome (IBS), adolescents (age 16-20 years) received two administrations - at baseline and after 6 weeks - of fresh allogeneic FMT from a Blastocystis-positive donor via nasoduodenal tube. The follow-up was 48 weeks. Blastocystis spp. presence, viability and subtyping were determined using microscopy, culture, PCR and sequencing.

RESULTS: Three recipients received FMT from one donor colonized with Blastocystis subtype 3 (ST3). At baseline, two recipients were negative for Blastocystis spp. and one recipient carried ST2. Culturing revealed viable Blastocystis spp. in fresh donor feces but not in frozen samples. After FMT with fresh feces, the two prior-negative recipients tested positive for the donor's ST3 at 12 weeks, but had lost this subtype by week 24 and 48. The recipient initially colonized with ST2 remained colonized with ST2 and did not acquire ST3. Transient adverse events occurred, but did not differ from patients treated with Blastocystis-negative FMT. No FMT-related serious adverse events emerged.

CONCLUSION: We present the first long-term data on viable Blastocystis spp. transmission via fresh FMT in three cases. Transient colonization with Blastocystis spp. was observed, without serious FMT-related adverse events.

RevDate: 2025-04-24
CmpDate: 2025-04-21

Deepti I, Chettri B, Mehra A, et al (2025)

Faecal microbiota transplantation for recurrent Clostridiodes difficile infection & its global regulatory landscape.

The Indian journal of medical research, 161(2):113-119.

For recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) is a known and useful treatment that involves introducing faeces from a healthy individual into the digestive tract of a diseased person. Clostridioides difficile is a substantial global health burden due to its high death rate in elderly populations and its ability to produce colitis and diarrhoea. Despite being used since millennia, FMT has recently become more well-known and two FMT products, namely Vowst and Rebyota also received FDA approval. Different nations address regulation in different ways. For instance, FMT is regulated as a drug in the US but is classified as a medicinal product in the UK. The regulatory frameworks among various European countries also vary; a working group, citing FMT as a transplant product, has requested for complete regulation. There are other classifications as well; in Australia, FMT is categorised as a biologic by the Therapeutic Goods Administration. Research indicates that FMT is beneficial in various illnesses, apart from CDI, due to its impact on the gut flora. Challenges include insufficient FMT product characterisation, ethical concerns, and limited hospital accessibility. There are still issues with data accessibility, security, and privacy, especially considering FMT's commercialisation. The official FMT recommendation for recurrent CDI is emphasised from the perspective of public health, with the argument that early implementation could limit antibiotic overuse and prevent antibiotic resistance. Initiatives like the Universal Stool Bank concept aim to streamline donor selection and distribution procedures to minimise operational restrictions.

RevDate: 2025-04-22
CmpDate: 2025-04-21

Abedi B, Karimian R, Bahari Z, et al (2024)

Absorbents therapy, as a conservative option, can improve kidney function in chronic kidney disease.

Archives of Razi Institute, 79(4):695-700.

Chronic kidney disease (CKD), also called chronic kidney failure, is increasingly recognized as a global public health problem in the entire world. It is characterized by slow, progressive, and irreversible loss in kidney physiology. Today, the prevalence of CKD is increasing dramatically. CKD can affect almost every organ system, including the cardiovascular system. Many treatments have been attempted for CKD, such as renal transplantation, hemodialysis (HD), and peritoneal dialysis (PD). At the end stage of CKD, HD is the most widely used therapy throughout the world. However, these options can decrease volume expansion and uremic solute retention and also increase patient survival. Furthermore, there are certain complications associated with the use of these methods. Previous studies have reported that the main side effects are headaches, muscle cramps, abdominal pain, hypotension, hypertension, vomiting, and constipation. Therefore, the investigation for better and more convenient dialysis techniques should continue, as well as the search for a better material to enhance the clearance of nitrogenous waste products from the body. The intestine has a significant effect on the clearance of nitrogenous waste products from the body, making it a potentially appropriate site for CKD management. The potential mechanism of the intestinal dialysis technique is that it can absorb excess fluids, uremic toxins, and electrolytes within the gastrointestinal (GI) tract and exert them in the feces before they can be absorbed into the blood. In the present review, we will focus on different absorbents as a conservative treatment to remove uremic waste metabolites from the GI tract for the improvement of kidney function in CKD.

RevDate: 2025-04-24

Wong MK, Armstrong E, Heirali AA, et al (2025)

Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.

bioRxiv : the preprint server for biology.

Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.

RevDate: 2025-04-24
CmpDate: 2025-04-24

Talwar C, Davuluri GVN, Kamal AHM, et al (2025)

Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.

Med (New York, N.Y.), 6(2):100517.

BACKGROUND: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

METHODS: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

FINDINGS: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease.

CONCLUSIONS: Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.

FUNDING: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.

RevDate: 2025-04-22

Rathore K, Shukla N, Naik S, et al (2025)

The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review.

Cureus, 17(3):e80810.

The gut microbiome plays a fundamental role in mental health, influencing mood, cognition, and emotional regulation through the gut-brain axis. This bidirectional communication system connects the gastrointestinal and CNS, facilitated by microbial metabolites, neurotransmitters, and immune interactions. Recent research highlights the association between gut dysbiosis and psychiatric disorders, including anxiety, depression, and stress-related conditions. Key findings indicate that altered microbial diversity, decreased short-chain fatty acid (SCFA) production, and increased neuroinflammation contribute to mental health disturbances. This paper explores the mechanism linking the gut microbiome to brain function, including microbial neurotransmitter synthesis, vagus nerve signaling, and hypothalamic-pituitary-adrenal (HPA) axis modulation. Additionally, it evaluates the potential of microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), in alleviating psychiatric symptoms. Microbiome sequencing and bioinformatics advances further support the development of personalized microbiome-based mental health interventions. Despite promising evidence, challenges such as inter-individual variability, methodological inconsistencies, and the need for longitudinal studies remain. Future research should focus on standardizing microbiome assessment techniques and optimizing therapeutic applications. Integrating precision psychiatry with microbiome-based diagnostics holds immense potential in transforming mental health treatment.

RevDate: 2025-04-22
CmpDate: 2025-04-20

Fehily SR, Wright EK, Basnayake C, et al (2025)

Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol.

BMJ open, 15(4):e094714.

INTRODUCTION: The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence.

METHODS AND ANALYSIS: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease.

ETHICS AND DISSEMINATION: Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.

RevDate: 2025-04-19
CmpDate: 2025-04-19

Hao Y, Wang C, Wang L, et al (2025)

Nondigestible stachyose alleviates cyclophosphamide-induced small intestinal mucosal injury in mice by regulating intestinal exosomal miRNAs, independently of the gut microbiota.

Food research international (Ottawa, Ont.), 209:116258.

Stachyose has traditionally been considered to exert prebiotic effects primarily through its interaction with gut microbiota. However, this study reveals a novel mechanism by which stachyose alleviates cyclophosphamide (CY)-induced small intestinal mucosa disruption by regulating the intestinal exosomal miRNAs, without relying on the gut microbiota. Specifically, stachyose significantly mitigates CY-caused damage to the intestinal permeability, oxidative stress, and the structure of intestinal villi and crypts in pseudo-germ-free (PGF) mice. The immunofluorescence staining and qPCR analyses show that stachyose treatment restores CY-caused abnormal changes on the levels of tight junction proteins including MUC2, Occludin, Claudin-1, and ZO-1, and pro-inflammatory cytokines including TNF-α, IL-1β, and IL-2. Furthermore, by conducting fecal miRNA transplantation experiment, we further demonstrated that, similar to stachyose, stachyose-shaped intestinal miRNAs protect against CY-induced intestinal mucosal damage in PGF mice. In summary, this study provides new scientific evidence for the direct interaction between nondigestible stachyose and the proximal small intestine. It also opens new avenues for further investigation into the systemic nutritional functions of stachyose, particularly the health benefits of stachyose in the upper gastrointestinal tract.

RevDate: 2025-04-19
CmpDate: 2025-04-19

Yang H, Zhao Y, Zhang R, et al (2025)

CiLi (Rosa roxburghii Tratt.) polyphenols improve colitis via gut microbiota-lipid mediator-immunity axis.

Food research international (Ottawa, Ont.), 209:116257.

Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.

RevDate: 2025-04-19
CmpDate: 2025-04-19

Zuo G, Li M, Guo X, et al (2025)

Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment.

Food research international (Ottawa, Ont.), 209:116207.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.

RevDate: 2025-04-19

Sahebi K, Arianejad M, Azadi S, et al (2025)

The Interplay between Gut Microbiome, Epigenetics, and Substance Use Disorders: from Molecular to Clinical Perspectives.

European journal of pharmacology pii:S0014-2999(25)00384-X [Epub ahead of print].

Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.

RevDate: 2025-04-22

Zhao Y, Zhao W, Chai X, et al (2025)

Reshaping the gut microbiota: A novel oppinion of Eucommiae cortex polysaccharide alleviate learning and memory impairments in Alzheimer's disease.

Journal of advanced research pii:S2090-1232(25)00269-3 [Epub ahead of print].

BACKGROUND: Alzheimer's disease (AD), which is a chronic neurodegenerative disorder, is marked by the progressive deteriorations in learning and memory capabilities. The microbiota-gut-brain axis has come to be regarded as a crucial element in relation to the pathogenesis as well as the treatment of AD. Eucommiae cortex polysaccharides (EPs), being among the most plentiful substances present in the Eucommiae cortex, show the potential to exert immunomodulatory and neuroprotective function. However, whether EPs are protective against AD and their mechanism of action remain to be investigated OBJECTIVES: We hypothesize that EPs can regulate brain glutamine metabolism through gut microbiota and the butyric acid metabolized by them, improve oxidative stress and autophagy in the brain, and thus alleviate AD.

METHODS: In the present study, we used EPs (0.25 % w/w in food) and fecal microbiota transplantation, as well as butyrate supplementation (0.1 M in water), to intervene in AD mice. Multi-omics were used to determine the mechanism by which EPs improve AD-related learning and memory impairments.

RESULTS: Our results suggest that EPs, functioning as a prebiotic, alleviated learning and memory impairments in AD mice. Mechanistically, EPs are able to reshape the gut microbiota, promote the growth of gut microbiota involved in short-chain fatty acid metabolism, particularly butyrate-producing microbes. The butyrate produced by these microbes improves the brain microenvironment by modulating oxidative stress and autophagy mediated by brain glutamate metabolism, improving learning and memory impairments in AD mice, and inhibiting the formation and deposition of beta-amyloid proteins. Fecal microbiota transplantation (FMT) and butyrate supplementation further confirm this conclusion.

CONCLUSIONS: Our results highlighted that EPs can alleviate learning and memory impairments in AD with a gut microbiota-dependent manner and that butyric acid metabolized by butyric acid-metabolizing bacteria in the gut plays a central role in regulating brain glutamine metabolism to improve brain microenvironmental homeostasis. Meanwhile, the present study provides new insights into the treatment of AD with natural products.

RevDate: 2025-04-19

Wang R, Gan C, Gong B, et al (2025)

Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 142:156756 pii:S0944-7113(25)00395-2 [Epub ahead of print].

BACKGROUND: Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.

PURPOSE: This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.

METHODS: The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.

RESULTS: A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.

CONCLUSION: TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.

RevDate: 2025-04-19

Vassallo GA, Dionisi T, De Vita V, et al (2025)

The role of fecal microbiota transplantation in diabetes.

Acta diabetologica [Epub ahead of print].

Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy for modulating gut dysbiosis in diabetes mellitus. This review critically evaluates preclinical and clinical evidence on FMT in type 1 (T1D) and type 2 diabetes (T2D). Studies suggest that FMT can restore microbial diversity, improve glycemic control, and modulate immune responses, with varying effects across diabetes subtypes. In T1D, preclinical models demonstrate that FMT influences regulatory T-cell expansion and β-cell preservation, though clinical translation remains limited. In T2D, FMT has shown transient improvements in insulin sensitivity, with sustained effects observed only in patients with specific microbiome signatures. However, heterogeneity in patient responses, donor variability, and methodological limitations complicate its clinical application. This review highlights the interplay between FMT, immune modulation, and microbial metabolism, advocating for phenotype-stratified trials and multi-omics integration to enhance therapeutic precision.

RevDate: 2025-04-20
CmpDate: 2025-04-18

Pan Q, Guo F, Chen J, et al (2025)

Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice.

Cellular & molecular biology letters, 30(1):49.

BACKGROUND: Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation.

METHODS: Here, lupus-prone MRL/MpJ-Fas[lpr] (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13.

RESULTS: Our results showed that early MSC treatment extended therapeutic effects up to 12 weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice.

CONCLUSIONS: This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota-tryptophan-AHR axis, thereby ameliorating SLE symptoms.

RevDate: 2025-04-18

Hirai J (2025)

Extended-pulsed Fidaxomicin Therapy for Recurrent Clostridioides difficile Infection After Standard Vancomycin and Fidaxomicin Failure: A Case Report.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy pii:S1341-321X(25)00106-0 [Epub ahead of print].

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea. Recurrence occurs in up to 60% of patients following multiple episodes, posing a major clinical challenge. While vancomycin (VCM) and fidaxomicin (FDX) are recommended first-line therapies, treatment failures and recurrences are not uncommon. Extended-pulsed fidaxomicin (EPFX) has been proposed to reduce recurrence, especially in high-risk patients, though the evidence remains limited for those with multiple prior relapses. We report the case of a 66-year-old man with advanced esophageal and gastric cancer who experienced four episodes of recurrent CDI despite standard treatment with VCM and FDX. Given the unavailability of bezlotoxumab (BEZ) in Japan and the limited accessibility of fecal microbiota transplantation (FMT), EPFX was selected as a salvage regimen. After both EPFX and pulse-tapered oral VCM were explained, the patient and physician elected to initiate EPFX, consisting of 200 mg twice daily for five days followed by 200 mg every other day for 20 days. No further recurrences were observed for over four months, and no adverse effects were noted. This case supports the use of EPFX in patients with multiple high-risk features-including advanced age, active malignancy, and prior treatment failures-despite the EXTEND trial's exclusion of patients with ≥3 recurrences. The favorable pharmacokinetic properties of FDX may have contributed to its efficacy. Importantly, the patient's medication, nutritional, and oncologic status remained stable throughout treatment, suggesting that EPFX played a pivotal role in achieving remission. EPFX may offer a viable option for patients with recurrent CDI refractory to standard therapies.

RevDate: 2025-04-19
CmpDate: 2025-04-18

Liu HJ, Wu MC, SY Gau (2025)

Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn's disease: Potential therapeutic targets.

World journal of gastroenterology, 31(13):102291.

This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.

RevDate: 2025-04-18

Bonazzi E, De Barba C, Lorenzon G, et al (2025)

Recent developments in managing luminal microbial ecology in patients with inflammatory bowel disease: from evidence to microbiome-based diagnostic and personalized therapy.

Expert review of gastroenterology & hepatology [Epub ahead of print].

INTRODUCTION: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science.

AREAS COVERED: we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed.

EXPERT OPINION: Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.

RevDate: 2025-04-20
CmpDate: 2025-04-17

Gefen R, Dourado J, Emile SH, et al (2025)

Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trials.

Techniques in coloproctology, 29(1):103.

BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile. FMT in inflammatory bowel disease, specifically ulcerative colitis (UC), has been investigated. We aimed to assess the efficacy of FMT in inducing UC remission.

METHODS: PubMed, Scopus, Google Scholar, and clinicaltrials.gov were searched for randomized control trials that assessed FMT in inducing UC remission. The primary outcome was combined clinical and endoscopic remission. Secondary outcomes were clinical remission, endoscopic remission, post-treatment overall adverse events, and colitis. Sensitivity analyses, meta-regression, bias assessment, and grading of certainty of evidence were performed.

RESULTS: A total of 14 studies including 600 patients (55.8% male; median age 40.7 years) were assessed. FMT was used in 299 patients and associated with significantly higher odds of combined clinical and endoscopic remission (OR 2.25, 95% CI 1.54, 3.3; p < 0.0001), clinical remission (OR 2.02, 95% CI 1.4, 2.93; p = 0.0002), and endoscopic remission (OR 1.95, 95% CI 1.17, 3.28; p = 0.011). The odds of post-treatment overall adverse events (OR 1.24, 95% CI 0.79, 1.95; p = 0.34) and colitis (OR 0.85, 95% CI 0.52, 1.93; p = 0.512) were similar between groups. Compared with baseline, FMT was more effective when biologics (OR 2.71), steroids (OR 2.27), or methotrexate (OR 3.07) were used as pre-FMT treatment. Oral delivery of FMT (OR 3.15) and pooled donors (OR 3.32) led to higher odds of remission. On meta-regression, pooled donors and methotrexate pre-treatment were associated with an increased likelihood of remission.

CONCLUSIONS: FMT is promising in inducing UC remission. Administration of medical treatments before FMT may help achieve higher remission rates. Current evidence shows that oral delivery of FMT and multidonor FMT may confer better results.

RevDate: 2025-04-17
CmpDate: 2025-04-17

Xia S, Yan C, Cai G, et al (2025)

Gut dysbiosis exacerbates inflammatory liver injury induced by environmentally relevant concentrations of nanoplastics via the gut-liver axis.

Journal of environmental sciences (China), 155:250-266.

As an emerging and potentially threatening pollutant, nanoplastics (NPs) have received considerable global attention. Due to their physical properties and diminutive size, NPs ingestion can more easily cross biological barriers and enter the human and animal body. Despite reports of hepatotoxicity associated with NPs, their impact and potential underlying mechanisms remain elusive. In this study, we investigated the impact of NPs at concentrations found in the environment on the gut flora, intestinal barrier function, liver pyroptosis, and inflammation in mice following 12 weeks of exposure. To further validate the involvement of gut flora in inflammatory liver damage caused by NPs, we utilized antibiotics to remove the intestinal flora and performed fecal microbiota transplantation. We confirmed that NPs exposure altered the gut microbiota composition, with a notable rise in the proportions of Alloprevotella and Ileibacterium while causing a decrease in the relative proportions of Dubosiella. This disruption also affected the gut barrier, increasing lipopolysaccharides in circulation and promoting liver pyroptosis. Importantly, mice receiving fecal transplants from NPs-treated mice showed intestinal barrier damage, liver pyroptosis, and inflammation. However, NPs effects on the intestinal barrier and liver pyroptosis were attenuated by antibiotics depletion of the commensal microbiota. In summary, our current research revealed that extended exposure to environmentally relevant concentrations of NPs resulted in inflammatory damage to the liver. Additionally, we have identified for the first time that imbalances in intestinal flora are crucial in liver pyroptosis induced by NPs.

RevDate: 2025-04-20

Adıgüzel E, Yılmaz ŞG, Atabilen B, et al (2025)

Microbiome modulation as a novel therapeutic modality for anxiety disorders: A review of clinical trials.

Behavioural brain research, 487:115595 pii:S0166-4328(25)00181-0 [Epub ahead of print].

Anxiety disorders are one of the major conditions in psychiatry characterized by symptoms such as worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Recent developments have drawn attention to the putative involvement of peripheral systems in the control of anxiety, and the gut microbiota has come to light as an emerging peripheral target for anxiety. The relationship between the gut-brain axis, a bidirectional communication network between the central nervous system (CNS) and enteric nervous system (ENS), and anxiety has been the subject of some recent studies. Therefore, this systematic review analyzed clinical trials evaluating the potential of microbiome modulation methods in mitigating and ameliorating anxiety disorders. Clinical studies on probiotic, prebiotic, synbiotic supplements, dietary interventions, and fecal microbiota transplantation in anxiety disorders were screened. All of the studies examined the effects of probiotic intervention. One of these studies compared a prebiotic-rich diet with probiotic supplementation. Longitudinal analyses showed that the probiotic intervention alleviated anxiety. However, most of the controlled studies reported that the probiotic intervention did not make a difference compared to placebo. Thus, the current findings suggest that it is too early to consider the promising role of microbiome modulation in the treatment of anxiety disorders. However, it is obvious that more clinical research is needed to clarify issues such as probiotic strains, prebiotic types, and their doses that may be effective on anxiety disorders.

RevDate: 2025-04-17

Vinit N, Glenisson M, Leroy J, et al (2025)

Anatomical correction and early outcomes of one-step ventral and dorsal proctoplasty in girls with low anorectal malformations.

European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie [Epub ahead of print].

INTRODUCTION: Rectoperineal (RPF) and rectovestibular fistula (RVF) are the most common forms of low anorectal malformations (ARM) in girls, and lead to difficult stooling, thus demanding early surgical correction. This study's aim was to assess early outcomes associated with one-step ventral and dorsal proctoplasty in RPF/RVF.

MATERIALS AND METHODS: All female infants who consecutively underwent one-step proctoplasty for RPF/RVF at our institution (2012-2022) were retrospectively included. Reviewed data included: age at procedure, congenital anomalies, fistula location, preoperative symptoms, intraoperative findings, operative time, postoperative complications, and bowel functional outcome. Success of the technique, defined as spontaneous bowel movement at last follow-up without anal dilation, was assessed. Secondary outcomes included resolution of preoperative symptoms, and Krickenbeck score and fecal continence in girls older than three at last follow-up. No preoperative bowel preparation was necessary.

RESULTS: None of the 77 included girls (median age at surgery: 3.2 months [2.3-7.3]) had prior colostomy. In every case, intraoperative findings included: ventral defect of the external anal sphincter, abnormal attachment of the bulbospongiosus muscles to the fistula and posterior ledge, thus justifying both ventral and dorsal reconstructions. The median operative time was 34 min [27-38], and the median hospital stay was 2 days [2-3]. Limited ventral skin dehiscence was the most common postoperative complication (31%), with limited effect on clinical outcome (one secondary anal stricture). No child required secondary colostomy or revision anoplasty. One child underwent secondary pull-through due to persistent megarectum. Preoperative symptoms resolved in 98% of cases. After a median follow-up of 27.6 months [9.8-48.3], all girls had spontaneous bowel movement and 21% had grade-2 constipation. The technique was successful in 97% of cases (two anal strictures treated with dilations).

CONCLUSIONS: RPF/RVF in female share abnormal anatomical characteristics. One-step ventral and dorsal proctoplasty allows precise anatomical correction of low ARM in girls.

RevDate: 2025-04-17

Zhang X, Yin Y, Chen Y, et al (2025)

Gut microbiota contributes to obstructive sleep apnea-induced hypertension by gut-heart axis in mice.

International immunopharmacology, 155:114667 pii:S1567-5769(25)00657-5 [Epub ahead of print].

BACKGROUND: The gut microbiome has been closely linked to obstructive sleep apnea (OSA)-associated hypertension (HTN). However, its precise role in the pathogenesis of OSA-induced HTN remains unclear.

METHODS: To clarify the causal relationship between gut dysbiosis and OSA-related HTN, C57BL6J mice were randomly assigned to four groups. Each group underwent fecal microbiota transplantation from healthy individuals (control), OSA patients (OSA group), OSA patients with pre-hypertension (OSA-pHTN group), or OSA patients with HTN (OSA-HTN group). The pro-hypertensive effects of the OSA gut microbiota were verified, and the composition and function of the gut microbiota were compared using 16S rDNA gene sequencing. Additionally, the gut microbiota-related lipopolysaccharide (LPS)/ Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway in aortic tissues was investigated.

RESULTS: Fecal microbiota transplantation induced increased systolic blood pressure and aortic injury in mice from the OSA, OSA-pHTN and OSA-HTN groups, whereas no significant injury was observed in the control group. These three groups exhibited dysbiosis and impaired intestinal barrier function as evidenced by a reduction in Akkermansia and decreased expression of zonula occludens-1 and Occludin proteins. In addition, LPS, TLR4 and phosphorylated NF-κB expression were increased in aortic tissue from the three groups, and immunofluorescence showed a significant upregulation of TLR4 expression in aortic endothelial cells compared to controls.

CONCLUSION: This study demonstrates the pro-hypertensive effects of gut microbiota in OSA, mediated through the gut-derived LPS/TLR4/NF-κB pathway. These findings may guide the development of therapeutic strategies focused on restoring gut microbiome homeostasis.

RevDate: 2025-04-17

Zhou H, Zhuang Y, Liang Y, et al (2025)

Curcumin exerts anti-tumor activity in colorectal cancer via gut microbiota-mediated CD8[+] T Cell tumor infiltration and ferroptosis.

Food & function [Epub ahead of print].

Colorectal cancer (CRC), as a high-incidence malignancy, continues to present significant challenges in prevention, screening, and treatment. Curcumin (Cur) exhibits notable anti-inflammatory and anticancer properties. Despite its poor solubility in water and low bioavailability, high concentrations of Cur are detected in the gastrointestinal tract after oral administration, suggesting that it may directly interact with the gut microbiota and exert regulatory effects. This study aims to explore the mechanisms by which Cur improves CRC by modulating gut microbiota. Firstly, we evaluated the effect of Cur on CRC cell viability in vitro using the MTT assay, and the results showed a significant inhibitory effect on CRC cell growth. The IC50 values for Cur in CT26 and RKO cells were 23.52 μM, 16.11 μM, and 13.62 μM at 24, 48, and 72 hours, respectively, and 26.3 μM, 16.52 μM, and 14.22 μM at 24, 48, and 72 hours, respectively. Cur induced apoptosis and caused G2 phase cell cycle arrest in tumor cells. Subsequently, we established a CRC mouse model. Oral administration of Cur at 15 mg kg[-1] and 30 mg kg[-1] inhibited CRC progression, as evidenced by reduced tumor volume, histological analysis, immunohistochemistry, and an increased number of CD8[+] T cells infiltrating the tumors. Ferroptosis in tumor cells was also observed. Cur partially restored the gut microbiota of CRC mice, altering the abundance and diversity of the gut microbiota and affecting serum metabolite distribution, with significant increases in the abundance of SCFA-producing microbes such as Lactobacillus and Kineothrix. To verify causality, we designed a fecal microbiota transplantation (FMT) experiment. Compared with CRC mice, the fecal microbiota from Cur-treated mice significantly alleviated CRC symptoms, including slowed tumor growth, enhanced CD8[+] T cell tumor infiltration, and induced ferroptosis in tumor cells. Additionally, when gut microbiota was depleted with antibiotics, Cur's antitumor effects disappeared, suggesting that Cur mitigates CRC in a gut microbiota-dependent manner. These findings provide new insights into the mechanisms underlying CRC and propose novel therapeutic interventions, emphasizing the interaction between gut microbiota and immune responses within the tumor immune microenvironment (TIME).

RevDate: 2025-04-19
CmpDate: 2025-04-17

Nista EC, Parello S, Brigida M, et al (2025)

Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review.

International journal of molecular sciences, 26(7):.

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Wu Z, Yan S, Zhang H, et al (2025)

Oral Sheep Milk-Derived Exosome Therapeutics for Cadmium-Induced Inflammatory Bowel Disease.

International journal of molecular sciences, 26(7):.

Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Bacteroides and Parabacteroides) were increased in FMT mice. SM-Exo treatment increased beneficial bacteria, particularly Lachnoclostridium, and activated the Cyclic Adenosine Monophosphate (cAMP) pathway, upregulating genes like Adcy1, Adcy3, CREB, and Sst. These changes were linked to reduced Cd-induced cell death and alleviation of colonic inflammation. In conclusion, SM-Exo appears to be a promising treatment for Cd-induced colitis, likely through modulation of the gut microbiota and activation of the cAMP pathway.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Ma B, Barathan M, Ng MH, et al (2025)

Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials.

International journal of molecular sciences, 26(7):.

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Xiong Y, Guo J, Yu W, et al (2025)

Molecular Mechanism of Microgravity-Induced Intestinal Flora Dysbiosis on the Abnormalities of Liver and Brain Metabolism.

International journal of molecular sciences, 26(7):.

Space flight has many adverse effects on the physiological functions of astronauts. Certain similarities have been observed in some physiological processes of rodents and astronauts in space, although there are also differences. These similarities make rodents helpful models for initial investigations into space-induced physiological changes. This study uses a 3D-Clinostat to simulate microgravity and explores the role of microgravity in space flight-induced liver and brain abnormalities by comparing changes in the gut microbiota, serum metabolites, and the function and physiological biochemistry of liver and brain tissues between the simulated microgravity (SMG) group mice and the wild type (WT) group mice. The study, based on hematoxylin-eosin (HE) staining, 16S sequencing technology, and non-targeted metabolomics analysis, shows that the gut tissue morphology of the SMG group mice is abnormal, and the structure of the gut microbiota and the serum metabolite profile are imbalanced. Furthermore, using PICRUST 2 technology, we have predicted the functions of the gut microbiota and serum metabolites, and the results indicate that the liver metabolism and functions (including lipid metabolism, amino acid metabolism, and sugar metabolism, etc.) of the SMG group mice are disrupted, and the brain tissue metabolism and functions (including neurotransmitters and hormone secretion, etc.) are abnormal, suggesting a close relationship between microgravity and liver metabolic dysfunction and brain dysfunction. Additionally, the high similarity in the structure of the gut microbiota and serum metabolite profile between the fecal microbiota transplant (FMT) group mice and the SMG group mice, and the physiological and biochemical differences in liver and brain tissues compared to the WT group mice, suggest that microgravity induces imbalances in the gut microbiota, which in turn triggers abnormalities in liver and brain metabolism and function. Finally, through MetaMapp analysis and Pearson correlation analysis, we found that valeric acid, a metabolite of gut microbiota, is more likely to be the key metabolite that relates to microgravity-induced gut microbiota abnormalities, disorders of amino acid and lipid metabolism, and further induced metabolic or functional disorders in the liver and brain. This study has significant practical application value for deepening the understanding of the adaptability of living organisms in the space environment.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Murgiano M, Bartocci B, Puca P, et al (2025)

Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools.

International journal of molecular sciences, 26(7):.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.

RevDate: 2025-04-19
CmpDate: 2025-04-17

Li X, Yang W, Weng Y, et al (2025)

Scutellarin Alleviates CCl4-Induced Liver Fibrosis by Regulating Intestinal Flora and PI3K/AKT Signaling Axis.

International journal of molecular sciences, 26(7):.

Liver fibrosis is a pathological manifestation of chronic liver disease developing to the terminal stage, and there is a lack of effective therapeutic drugs in clinical practice. Scutellarin (SCU) is a flavonoid extracted from Erigeron breviscapus (Vaniot.) Hand.-Mazz., which has significant anti-liver-fibrosis efficacy, but its mode of action remains incompletely understood. A liver fibrosis model was built with male Sprague Dawley rats induced with the disease by CCl4 to evaluate the therapeutic effect of drugs. 16S rRNA sequencing and metabolomics were used to analyze the regulatory effects of SCU on intestinal flora and host metabolism; antibiotics were administered to eliminate gut microbiota and fecal microbiota transplantation (FMT) experiments were used to verify the mechanism. The mechanistic basis underlying SCU's hepatic anti-fibrotic effects was screened by network pharmacology combined with transcriptomics, combined with molecular docking, qPCR, and WB verification. The results showed that SCU may play an anti-liver-fibrosis role by correcting the imbalance of gut flora and regulating the linoleic acid and purine metabolic pathways. In addition, SCU can downregulate the levels of proteins and genes related to the PI3K/AKT axis. In summary, SCU alleviates liver fibrosis by reversing intestinal flora imbalance, regulating the metabolic profile, and inhibiting the PI3K/AKT axis.

RevDate: 2025-04-17
CmpDate: 2025-04-17

Beyoğlu D, JR Idle (2025)

The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.

International journal of molecular sciences, 26(7):.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.

RevDate: 2025-04-17

Ismeurt-Walmsley C, Giannoni P, Servant F, et al (2025)

The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease.

mBio [Epub ahead of print].

UNLABELLED: The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analyzed the fecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted fecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory performance, whereas FMT from mice housed in SOPF facility did not induce memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born animals in a conventional facility resulted in the reappearance of specific microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show a strong impact of housing conditions on microbiota-associated phenotypes and question the relevance of breeding preclinical models in specific pathogen-free (SPF) facilities.

IMPORTANCE: Housing conditions affect the composition of the gut microbiota. Gut microbiota of 6-month-old conventionally bred Alzheimer's mice is dysbiotic. Gut dysbiosis is absent in Alzheimer's mice housed in highly sanitized facilities. Transfer of fecal microbiota from conventionally bred mice affects cognition. Microbiota of mice housed in highly sanitized facilities has no effect on cognition.

RevDate: 2025-04-17

Olesen RH, Larsen EB, Rubak T, et al (2025)

Cost-Effectiveness of Hospital-at-Home and Fecal Microbiota Transplantation in Treating Older Patients With Clostridioides difficile.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8113578 [Epub ahead of print].

BACKGROUND: Clostridioides difficile infection (CDI) primarily affects older patients with comorbid conditions and has a high mortality rate. Fecal microbiota transplantation (FMT) is effective and cost-effective for CDI. In a recent study, we demonstrated the clinical benefits of combining hospital-at-home care with FMT for older patients with CDI, but its cost-effectiveness remains unknown. The current study aimed to evaluate the cost-effectiveness of the intervention in patients aged ≥70 years with CDI, compared with standard treatment.

METHODS: The cost-utility analysis was conducted using data from a randomized clinical trial enrolling 217 patients, assessing the cost-effectiveness of the intervention over 90 days. Resource use was assessed from a healthcare sector perspective. Missing data were handled with proxy replacement and multiple imputation. Sensitivity analyses included probabilistic analysis, complete case analysis, adjustment of key unit prices, and a hospital perspective. A willingness-to-pay threshold was set to €22 994 or $24 863 per quality-adjusted life year (QALY).

RESULTS: In the base case analysis, the intervention was dominant, with mean cost savings of €2556 ($2764) and a mean gain of 0.004 QALY. Although resource use was higher, the intervention resulted in an average reduction of 6 hospital admission days per patient and increased odds of clinical resolution. The results remained robust across different perspectives, the exclusion of patients with missing data, and variations in hospital admission costs.

CONCLUSIONS: In patients aged ≥70 years with CDI, an intervention combining hospital-at-home care and FMT is cost-effective compared with standard treatment. The cost-effectiveness is mainly driven by fewer hospital admission days.

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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.

Electronic Scholarly Publishing
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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 )