Gut Microbes最新文献

{"title":"Genomic and functional co-diversification imprint African Hominidae microbiomes to signal dietary and lifestyle adaptations.","authors":"Saria Otani, Marie Louise Jespersen, Christian Brinch, Frederik Duus Møller, Bo Pilgaard, Emilie Egholm Bruun Jensen, Pimlapas Leekitcharoenphon, Christina Aaby Svendsen, Amalie H Aarestrup, Tolbert Sonda, Teresa J Sylvina, Jeff Leach, Alexander Piel, Fiona Stewart, Panagiotis Sapountzis, Paul E Kazyoba, Happiness Kumburu, Frank M Aarestrup","doi":"10.1080/19490976.2025.2484385","DOIUrl":"10.1080/19490976.2025.2484385","url":null,"abstract":"<p><p>In the diverse landscape of African hominids, the obligate relationship between the host and its microbiome narrates signals of adaptation and co-evolution. Sequencing 546 African hominid metagenomes, including those from indigenous Hadza and wild chimpanzees, identified similar bacterial richness and diversity surpassing those of westernized populations. While hominids share core bacterial communities, they also harbor distinct, population-specific bacterial taxa tailored to specific diets, ecology and lifestyles, differentiating non-indigenous and indigenous humans and chimpanzees. Even amongst shared bacterial communities, several core bacteria have co-diversified to fulfil unique dietary degradation functions within their host populations. These co-evolutionary trends extend to non-bacterial elements, such as mitochondrial DNA, antimicrobial resistance, and parasites. Our findings indicate that microbiome-host co-adaptations have led to both taxonomic and within taxa functional displacements to meet host physiological demands. The microbiome, in turn, transcends its taxonomic interchangeable role, reflecting the lifestyle, ecology and dietary history of its host.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2484385"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome signatures of virulence in the oral-gut-brain axis influence Parkinson's disease and cognitive decline pathophysiology.","authors":"Frederick Clasen, Suleyman Yildirim, Muzaffer Arıkan, Fernando Garcia-Guevara, Lűtfű Hanoğlu, Nesrin H Yılmaz, Aysu Şen, Handan Kaya Celik, Alagoz Aybala Neslihan, Tuǧçe Kahraman Demir, Zeynep Temel, Adil Mardinoglu, David L Moyes, Mathias Uhlen, Saeed Shoaie","doi":"10.1080/19490976.2025.2506843","DOIUrl":"10.1080/19490976.2025.2506843","url":null,"abstract":"<p><p>The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2506843"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematically-designed mixtures outperform single fibers for gut microbiota support.","authors":"T M Cantu-Jungles, V Agamennone, T J Van den Broek, F H J Schuren, B Hamaker","doi":"10.1080/19490976.2024.2442521","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442521","url":null,"abstract":"<p><p>Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled <i>in vitro</i> fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components <i>in vitro</i> using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the <i>Clostridium</i> cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442521"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Desulfovibrio vulgaris</i> flagellin exacerbates colorectal cancer through activating LRRC19/TRAF6/TAK1 pathway.","authors":"Yue Dong, Fanyi Meng, Jingyi Wang, Jingge Wei, Kexin Zhang, Siqi Qin, Mengfan Li, Fucheng Wang, Bangmao Wang, Tianyu Liu, Weilong Zhong, Hailong Cao","doi":"10.1080/19490976.2024.2446376","DOIUrl":"https://doi.org/10.1080/19490976.2024.2446376","url":null,"abstract":"<p><p>The initiation and progression of colorectal cancer (CRC) are intimately associated with genetic, environmental and biological factors. <i>Desulfovibrio vulgaris</i> (DSV), a sulfate-reducing bacterium, has been found excessive growth in CRC patients, suggesting a potential role in carcinogenesis. However, the precise mechanisms underlying this association remain incompletely understood. We have found <i>Desulfovibrio</i> was abundant in high-fat diet-induced <i>Apc</i>^<i>min/+</i> mice, and DSV, a member of <i>Desulfovibrio</i>, triggered colonocyte proliferation of germ-free mice. Furthermore, the level of DSV progressively rose from healthy individuals to CRC patients. Flagella are important accessory structures of bacteria, which can help them colonize and enhance their invasive ability. We found that <i>D. vulgaris</i> flagellin (DVF) drove the proliferation, migration, and invasion of CRC cells and fostered the growth of CRC xenografts. DVF enriched the epithelial-mesenchymal transition (EMT)-associated genes and characterized the facilitation of DVF on EMT. Mechanistically, DVF induced EMT through a functional transmembrane receptor called leucine-rich repeat containing 19 (LRRC19). DVF interacted with LRRC19 to modulate the ubiquitination of tumor necrosis factor receptor-associated factor (TRAF)6, rather than TRAF2. This interaction drove the ubiquitination of pivotal molecule TAK1, further enhancing its autophosphorylation and ultimately contributing to EMT. Collectively, DVF interacts with LRRC19 to activate the TRAF6/TAK1 signaling pathway, thereby promoting the EMT of CRC. These data shed new light on the role of gut microbiota in CRC and establish a potential clinical therapeutic target.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2446376"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modelling framework to characterize the impact of antibiotics on the gut microbiota diversity.","authors":"Carlos Olivares, Etienne Ruppé, Stéphanie Ferreira, Tanguy Corbel, Antoine Andremont, Jean de Gunzburg, Jeremie Guedj, Charles Burdet","doi":"10.1080/19490976.2024.2442523","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442523","url":null,"abstract":"<p><p>Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442523"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.","authors":"Evelien Floor, Jinyi Su, Maitrayee Chatterjee, Elise S Kuipers, Noortje IJssennagger, Faranak Heidari, Laura Giordano, Richard W Wubbolts, Silvia M Mihăilă, Daphne A C Stapels, Yvonne Vercoulen, Karin Strijbis","doi":"10.1080/19490976.2024.2434685","DOIUrl":"https://doi.org/10.1080/19490976.2024.2434685","url":null,"abstract":"<p><p>The intestinal mucosal barrier is a dynamic system that allows nutrient uptake, stimulates healthy microbe-host interactions, and prevents invasion by pathogens. The mucosa consists of epithelial cells connected by cellular junctions that regulate the passage of nutrients covered by a mucus layer that plays an important role in host-microbiome interactions. Mimicking the intestinal mucosa for <i>in vitro</i> assays, particularly the generation of a mucus layer, has proven to be challenging. The intestinal cell-line Caco-2 is widely used in academic and industrial laboratories due to its capacity to polarize, form an apical brush border, and reproducibly grow into confluent cell layers in different culture systems. However, under normal culture conditions, Caco-2 cultures lack a mucus layer. Here, we demonstrate for the first time that Caco-2 cultures can form a robust mucus layer when cultured under air-liquid interface (ALI) conditions on Transwell inserts with addition of vasointestinal peptide (VIP) in the basolateral compartment. We demonstrate that unique gene clusters are regulated in response to ALI and VIP single stimuli, but the ALI-VIP combination treatment resulted in a significant upregulation of multiple mucin genes and proteins, including secreted MUC2 and transmembrane mucins MUC13 and MUC17. Expression of tight junction proteins was significantly altered in the ALI-VIP condition, leading to increased permeability to small molecules. Commensal <i>Lactiplantibacillus plantarum</i> bacteria closely associated with the Caco-2 mucus layer and differentially colonized the surface of the ALI cultures. Pathogenic <i>Salmonella enterica</i> were capable of invading beyond the mucus layer and brush border. In conclusion, Caco-2 ALI-VIP cultures provide an accessible and straightforward way to culture an <i>in vitro</i> intestinal mucosal model with improved biomimetic features. This novel <i>in vitro</i> intestinal model can facilitate studies into mucus and epithelial barrier functions and in-depth molecular characterization of pathogenic and commensal microbe-mucus interactions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2434685"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia.","authors":"Morgane M Thibaut, Martin Roumain, Edwige Piron, Justine Gillard, Axelle Loriot, Audrey M Neyrinck, Julie Rodriguez, Isabelle Massart, Jean-Paul Thissen, Joshua R Huot, Fabrizio Pin, Andrea Bonetto, Nathalie M Delzenne, Giulio G Muccioli, Laure B Bindels","doi":"10.1080/19490976.2025.2449586","DOIUrl":"10.1080/19490976.2025.2449586","url":null,"abstract":"<p><p>Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as <i>Xylanibacter rodentium</i>, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i>, TDCA prevented myotube atrophy, whereas <i>in vivo</i> hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2449586"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crystal structure of the toxin EspC from enteropathogenic <i>Escherichia coli</i> reveals the mechanism that governs host cell entry and cytotoxicity.","authors":"Akila U Pilapitiya, Lilian Hor, Jing Pan, Lakshmi C Wijeyewickrema, Robert N Pike, Denisse L Leyton, Jason J Paxman, Begoña Heras","doi":"10.1080/19490976.2025.2483777","DOIUrl":"10.1080/19490976.2025.2483777","url":null,"abstract":"<p><p>Enteropathogenic <i>E. coli</i> (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic attaching and effacing lesions on the intestinal epithelium. In this study, we present the crystal structure of the EspC passenger domain (α^EspC) revealing a toxin comprised a serine protease attached to a large β-helix with additional subdomains. Using various modified EspC expression constructs, alongside type III secretion system-mediated cell internalization assays, we dissect how the α^EspC structural features enable toxin entry into the intestinal epithelium to cause cell cytotoxicity.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2483777"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19.","authors":"Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Valentin Sencio, Nicolas Benech, Marybeth Creskey, Fabiola Silva Angulo, Lou Delval, Cyril Robil, Philippe Gosset, Arnaud Machelart, Joel Haas, Amandine Descat, Jean François Goosens, Delphine Beury, Florence Maurier, David Hot, Isabelle Wolowczuk, Harry Sokol, Xu Zhang, Marco Aurélio Ramirez Vinolo, François Trottein","doi":"10.1080/19490976.2025.2486511","DOIUrl":"10.1080/19490976.2025.2486511","url":null,"abstract":"<p><p>Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (<i>Eubacterium</i>, <i>Oscillospiraceae</i>, <i>Lawsonibacter</i>) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486511"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota alterations induced by Roux-en-Y gastric bypass result in glucose-lowering by enhancing intestinal glucose excretion.","authors":"Zhigang Ke, Zongshi Lu, Fan Li, Qingyuan Zhao, Xianhong Jiang, Zhihao Hu, Fang Sun, Zongcheng He, Yi Tang, Qing Li, Stefan van Oostendorp, Xiao Chen, Qiuyue He, Yong Wang, Zhiming Zhu, Weidong Tong","doi":"10.1080/19490976.2025.2473519","DOIUrl":"10.1080/19490976.2025.2473519","url":null,"abstract":"<p><p>Roux-en-Y gastric bypass (RYGB) results in glucose-lowering in patients with type 2 diabetes mellitus (T2DM) and may be associated with increased intestinal glucose excretion. However, the contribution of intestinal glucose excretion to glycemic control after RYGB and its underlying mechanisms are not fully elucidated. Here, we confirmed that intestinal glucose excretion significantly increased in obese rats after RYGB, which was negatively correlated with postoperative blood glucose levels. Moreover, we also found that the contribution of Biliopancreatic limb length, an important factor affecting glycemic control after RYGB, to the improvement of glucose metabolism after RYGB attributed to the enhancement of intestinal glucose excretion. Subsequently, we further determined through multiple animal models that intestinal glucose excretion is physiological rather than pathological and plays a crucial role in maintaining glucose homeostasis in the body. Finally, we employed germ-free mice colonized with fecal samples from patients and rats to demonstrate that enhanced intestinal glucose excretion after RYGB is directly modulated by the surgery-induced changes in the gut microbiota. These results indicated that the gut microbiota plays a direct causal role in the hypoglycemic effect of RYGB by promoting intestinal glucose excretion, which may provide new insights for developing gut microbiota-based therapies for T2DM.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473519"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}