Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-03-13DOI: 10.1080/19490976.2025.2474151
Florent Kempf, Rosanna Drumo, Anne Marie Chaussé, Pierrette Menanteau, Tereza Kubasova, Sylvie Roche, Anne Christine Lalmanach, Rodrigo Guabiraba, Thierry Chaumeil, Guillaume Larivière-Gauthier, Ignacio Caballero-Posadas, Béatrice Laroche, Ivan Rychlík, Isabelle Virlogeux-Payant, Philippe Velge
{"title":"The immune response modulated by inoculation of commensal bacteria at birth impacts the gut microbiota and prevents <i>Salmonella</i> colonization.","authors":"Florent Kempf, Rosanna Drumo, Anne Marie Chaussé, Pierrette Menanteau, Tereza Kubasova, Sylvie Roche, Anne Christine Lalmanach, Rodrigo Guabiraba, Thierry Chaumeil, Guillaume Larivière-Gauthier, Ignacio Caballero-Posadas, Béatrice Laroche, Ivan Rychlík, Isabelle Virlogeux-Payant, Philippe Velge","doi":"10.1080/19490976.2025.2474151","DOIUrl":"10.1080/19490976.2025.2474151","url":null,"abstract":"<p><p>Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with <i>Salmonella</i> Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after <i>Salmonella</i> infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited <i>Salmonella</i> colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates <i>Salmonella</i> colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against <i>Salmonella</i> and possibly other pathogens.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474151"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624416","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-03-20DOI: 10.1080/19490976.2025.2476563
Sophie Castonguay-Paradis, Élisabeth Demers-Potvin, Gabrielle Rochefort, Sébastien Lacroix, Julie Perron, Cyril Martin, Nicolas Flamand, Frédéric Raymond, Vincenzo Di Marzo, Alain Veilleux
{"title":"Seasonal variations in circulating endocannabinoidome mediators and gut microbiota composition in humans.","authors":"Sophie Castonguay-Paradis, Élisabeth Demers-Potvin, Gabrielle Rochefort, Sébastien Lacroix, Julie Perron, Cyril Martin, Nicolas Flamand, Frédéric Raymond, Vincenzo Di Marzo, Alain Veilleux","doi":"10.1080/19490976.2025.2476563","DOIUrl":"10.1080/19490976.2025.2476563","url":null,"abstract":"<p><strong>Background: </strong>The human gut microbiome-endocannabinoidome axis is crucial for several homeostatic processes, including inflammation and energy metabolism, and is influenced by many endogenous and exogenous factors, such as dietary habits. Changes in the gut microbiome in response to seasonal variations were previously reported and tentatively attributed to shifts in dietary patterns. However, there is a need for longitudinal studies in industrialized populations to comprehensively explore seasonal variations independently of lifestyle confounding factors.</p><p><strong>Objective: </strong>To investigate the longitudinal effects of seasonal variations on the composition of the gut microbiome and the circulating levels of endocannabinoidome mediators in humans, while elucidating the contributing factors underlying these changes.</p><p><strong>Methods: </strong>Plasma and fecal samples were collected at the end of both the winter and summer in a longitudinal cohort of 48 individuals living in Québec City (Canada). Dietary habits, medical history, fecal microbiota taxonomic composition and plasma levels of circulating <i>N‑</i>acyl‑ethanolamines (NAEs) and 2<i>‑</i>monoacyl-glycerols (2<i>‑</i>MAGs) were obtained at each time point.</p><p><strong>Results: </strong>Lower circulating levels of most NAEs were observed at the end of summer. These changes were accompanied by a reduction in the relative abundance of the <i>Bifidobacteriaceae</i> and <i>Lachnospiraceae</i> families, along with an increase in the abundance of the <i>Bacteroidaceae</i> and <i>Ruminococcaceae</i> families. These seasonal variations were not associated with concurrent changes in adiposity parameters, dietary intakes, physical activity habits, or vitamin D status. Importantly, the magnitude of the shift in gut microbiota composition from winter to summer was found to be associated with the seasonal variations in circulating endocannabinoidome (eCBome) mediators.</p><p><strong>Conclusion: </strong>This study identified specific seasonal changes in gut microbiota composition and circulating levels of several NAEs, which were not associated with vitamin D status and lifestyle habits. It underscores the importance of the gut microbiota-endocannabinoidome axis in the pathophysiology of seasonal changes, and of considering seasons in clinical trials on these systems.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476563"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663341","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-02-23DOI: 10.1080/19490976.2025.2470372
Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu
{"title":"Upregulation of <i>Lactobacillus spp</i>. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.","authors":"Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu","doi":"10.1080/19490976.2025.2470372","DOIUrl":"10.1080/19490976.2025.2470372","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic <i>Lactobacillus</i>, particularly <i>L. reuteri</i>. Treatment with <i>L. reuteri</i> significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of <i>L. reuteri</i>, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal <i>Lactobacillus</i> abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of <i>L. reuteri</i> in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic <i>Lactobacillus</i> may offer a novel therapeutic strategy for PDAC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2470372"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482959","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 microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.","authors":"Andi Chen, Chengqian Teng, Jianjie Wei, Xuyang Wu, Honghong Zhang, Pinzhong Chen, Dingliang Cai, Haitao Qian, Hui Zhu, Xiaochun Zheng, Xiaohui Chen","doi":"10.1080/19490976.2025.2471015","DOIUrl":"10.1080/19490976.2025.2471015","url":null,"abstract":"<p><p>Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2471015"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500669","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-01-22DOI: 10.1080/19490976.2025.2455503
Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S Harris, Yong Ge
{"title":"<i>Faecalibacterium prausnitzii</i> regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice.","authors":"Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S Harris, Yong Ge","doi":"10.1080/19490976.2025.2455503","DOIUrl":"10.1080/19490976.2025.2455503","url":null,"abstract":"<p><p>The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. <i>Faecalibacterium prausnitzii</i> is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct <i>F. prausnitzii</i> strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel <i>F. prausnitzii</i> strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Turicibacter</i>. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch <i>in vitro</i> and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of <i>F. prausnitzii</i>.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455503"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004535","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-05-23DOI: 10.1080/19490976.2025.2507775
Adrián Cortés-Martín, Colin Buttimer, Jessie L Maier, Ciara A Tobin, Lorraine A Draper, R Paul Ross, Manuel Kleiner, Colin Hill, Andrey N Shkoporov
{"title":"Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages.","authors":"Adrián Cortés-Martín, Colin Buttimer, Jessie L Maier, Ciara A Tobin, Lorraine A Draper, R Paul Ross, Manuel Kleiner, Colin Hill, Andrey N Shkoporov","doi":"10.1080/19490976.2025.2507775","DOIUrl":"10.1080/19490976.2025.2507775","url":null,"abstract":"<p><p>Bacteriophages (phages) and bacteria within the gut microbiome persist in long-term stable coexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employ a variety of mechanisms to evade phage infection, while phages rely on counterstrategies to overcome these defenses. Among the most abundant phages in the gut are the crAss-like phages that infect members of the order Bacteroidales, in particular, genus <i>Bacteroides</i>. In this study, we explored some of the mechanisms enabling the co-existence of four phage-Bacteroidales host pairs <i>in vitro</i> using a multi-omics approach (transcriptomics, proteomics and metabolomics). These included three <i>Bacteroides</i> species paired with three crAss-like phages (<i>Bacteroides intestinalis</i> and фcrAss001, <i>Bacteroides xylanisolvens</i> and фcrAss002, and an acapsular mutant of <i>Bacteroides thetaiotaomicron</i> with DAC15), and <i>Parabacteroides distasonis</i> paired with the siphovirus фPDS1. We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechanism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternative resistance mechanisms, while potentially less efficient than CPS phase variation, can be activated to support bacterial survival by regulating gene expression and resulting in metabolic adaptations, particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phase variation, enable bacterial populations to persist in the presence of phages, and <i>vice versa</i>. An acapsular variant of <i>B. thetaiotaomicron</i> demonstrated broader transcriptomic, proteomic, and metabolomic changes, supporting the involvement of additional resistance mechanisms beyond CPS variation. This study advances our understanding of long-term phage-host interaction, offering insights into the long-term persistence of crAss-like phages and extending these observations to other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions is essential for designing effective phage therapies and improving human health through targeted microbiome interventions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2507775"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127486","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-06-04DOI: 10.1080/19490976.2025.2509281
Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson
{"title":"Impact of peripheral circadian misalignment and alcohol on the resiliency of intestinal barrier and microbiota.","authors":"Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson","doi":"10.1080/19490976.2025.2509281","DOIUrl":"10.1080/19490976.2025.2509281","url":null,"abstract":"<p><p>Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to fill this knowledge gap by testing the hypothesis that: (1) WTE worsens alcohol-induced disruption of intestinal barrier integrity and (2) decreased intestinal barrier resiliency to alcohol effects by WTE-disrupted circadian is, at least in part, due to microbiota dysbiosis. Alcohol (20% v/v) and a restricted timed-food paradigm were administered to PERIOD2 luciferase (PER2:LUC) reporter BL/6 mice for 10 weeks. Intestinal barrier integrity, intestinal (stool) microbiota, and microbial metabolites (cecal-derived) were examined. Peripheral circadian misalignment exacerbated alcohol-induced disruption of intestinal barrier integrity (tight junctional proteins) leading to increased intestinal permeability (<i>p</i> < 0.05). In addition, alcohol consumption changed the intestinal microbiota community, decreasing beneficial short-chain fatty acid-producing taxa. Further, we recapitulated the in vivo phenotype in a colonic organoid model and demonstrated that microbial metabolites from circadian-disrupted, alcohol-fed mice mediate decreased resiliency of intestinal epithelial barrier function. Peripheral circadian misalignment through food timing decreases the resiliency of the intestinal barrier to alcohol-induced injury and this effect is mediated through dysbiotic microbiota metabolites.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2509281"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215670","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-04-27DOI: 10.1080/19490976.2025.2489071
Jelle Slager, Hanna L Simpson, Ranko Gacesa, Lianmin Chen, Ineke L Tan, Jody Gelderloos, Astrid Maatman, Cisca Wijmenga, Alexandra Zhernakova, Jingyuan Fu, Rinse K Weersma, Gieneke Gonera, Iris H Jonkers, Sebo Withoff
{"title":"High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation.","authors":"Jelle Slager, Hanna L Simpson, Ranko Gacesa, Lianmin Chen, Ineke L Tan, Jody Gelderloos, Astrid Maatman, Cisca Wijmenga, Alexandra Zhernakova, Jingyuan Fu, Rinse K Weersma, Gieneke Gonera, Iris H Jonkers, Sebo Withoff","doi":"10.1080/19490976.2025.2489071","DOIUrl":"https://doi.org/10.1080/19490976.2025.2489071","url":null,"abstract":"<p><strong>Background: </strong>Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.</p><p><strong>Methods: </strong>To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.</p><p><strong>Results: </strong>Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of <i>Clostridium sp. CAG:253</i>, <i>Roseburia hominis</i>, and <i>Eggerthella lenta</i>, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of <i>Eubacterium rectale</i>, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.</p><p><strong>Conclusion: </strong>Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2489071"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011967","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":"Time-restricted feeding promotes glucagon-like peptide-1 secretion and regulates appetite via tryptophan metabolism of gut <i>Lactobacillus</i> in pigs.","authors":"Qiuke Li, Ding Tan, Shijie Xiong, Kaifan Yu, Yong Su, Weiyun Zhu","doi":"10.1080/19490976.2025.2467185","DOIUrl":"10.1080/19490976.2025.2467185","url":null,"abstract":"<p><p>Previous clinical trials have shown that time-restricted feeding can be involved in regulating the metabolic health of humans and animals. However, the underlying mechanism has not been fully explored. In this study, the pig model was employed to simulate four prevalent human eating habits, with the aim of investigating the impact of gut microbiota and microbial metabolites on gut hormone secretion and appetite regulation. Compared to the <i>ad libitum</i> feeding (ALF) pattern, three time-restricted feeding patterns reduced total food intake and eating time. Meanwhile, three time-restricted feeding patterns induced elevated levels of serum and hypothalamic glucagon-like peptide-1 (GLP-1), while suppressing reward-related circuits in the hypothalamus. It is noteworthy that the early time-restricted feeding (eTRF) pattern increased the number of intestinal enteroendocrine cells (EECs) compared to ALF. Metagenomic and metabonomic analyses revealed that three time-restricted feeding patterns induced colonization of <i>Lactobacillus</i> and significantly increased the levels of its metabolite, indole-3-lactic acid (ILA). Dietary supplementation with ILA exhibited an increasing trend in fasting serum GLP-1 level of piglets. <i>In vitro</i> studies with pig intestinal organoids showed the <i>Lactobacillus</i> metabolite ILA enhanced GLP-1 secretion through the promotion of intestinal stem cell differentiation into EECs, rather than activating the ability of EECs to secrete GLP-1. Overall, time-restricted feeding promoted GLP-1 secretion and affected long-term appetite regulation by promoting the colonization of <i>Lactobacillus</i> and modulating microbial tryptophan metabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467185"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416679","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}