Pub Date : 2026-12-31Epub Date: 2026-01-03DOI: 10.1080/19490976.2025.2611545
Na Li, Xiaohuan Guo
Colonization resistance is a fundamental host defense mechanism that relies on the synergistic interaction between the gut microbiota and the host immune system to prevent enteric pathogen colonization and infection. This review synthesizes current knowledge of the multifaceted mechanisms governing colonization resistance against intestinal pathogens. We examine how commensal microbes directly suppress pathogens through niche and nutrient competition, contact-dependent inhibition, and the production of antimicrobial compounds and metabolites. From the host perspective, we outline the essential roles of gut barriers, innate and adaptive immunity, and antimicrobial peptides in maintaining microbiota homeostasis while selectively restricting pathogen expansion. We also emphasize the role of IL-22 signaling and its regulation of epithelial glycosylation, which modulates nutrient availability and shapes microbial competitiveness. Finally, we discuss key challenges and future research directions in colonization resistance and related translational research, with the goal of informing novel strategies to prevent and treat intestinal infections and inflammatory diseases.
{"title":"The gut microbiota and host immunity synergistically orchestrate colonization resistance.","authors":"Na Li, Xiaohuan Guo","doi":"10.1080/19490976.2025.2611545","DOIUrl":"10.1080/19490976.2025.2611545","url":null,"abstract":"<p><p>Colonization resistance is a fundamental host defense mechanism that relies on the synergistic interaction between the gut microbiota and the host immune system to prevent enteric pathogen colonization and infection. This review synthesizes current knowledge of the multifaceted mechanisms governing colonization resistance against intestinal pathogens. We examine how commensal microbes directly suppress pathogens through niche and nutrient competition, contact-dependent inhibition, and the production of antimicrobial compounds and metabolites. From the host perspective, we outline the essential roles of gut barriers, innate and adaptive immunity, and antimicrobial peptides in maintaining microbiota homeostasis while selectively restricting pathogen expansion. We also emphasize the role of IL-22 signaling and its regulation of epithelial glycosylation, which modulates nutrient availability and shapes microbial competitiveness. Finally, we discuss key challenges and future research directions in colonization resistance and related translational research, with the goal of informing novel strategies to prevent and treat intestinal infections and inflammatory diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2611545"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12773493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892457","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}
Dysbiosis of the gut microbiota is strongly associated with a wide range of pathologies, including various types of cancer. Porphyromonas gingivalis (P. gingivalis), an oral bacterium, is implicated in the development of colorectal cancer (CRC), and although the exact mechanisms by which P. gingivalis contributes to CRC remain unclear, and emerging evidence suggests that various bacterial elements are involved in the bacterium's pathogenic effects. Here, we show that P. gingivalis secreted factors promote CRC neoplasia progression by modulating both the Wnt/β-catenin and the Hippo-YAP signaling pathways. Using specific inhibitors and P. gingivalis mutant strains, our findings demonstrate that cysteine proteases, specifically Lysin-gingipain (Kgp) and Argin-gingipain A (RgpA), as well as hydrogen sulfide (H₂S), strongly induce the expression of epithelial-mesenchymal transition (EMT) markers, leading to cell detachment and increased motility. These findings reveal a novel connection between microbial virulence and defense mechanisms, such as H₂S, and host cell transformation, suggesting a potential role for bacterial secreted factors in driving CRC neoplasia.
肠道菌群的生态失调与多种疾病密切相关，包括各种类型的癌症。牙龈卟啉单胞菌（P. gingivalis）是一种口腔细菌，与结直肠癌（CRC）的发展有关，尽管牙龈卟啉单胞菌导致CRC的确切机制尚不清楚，但新出现的证据表明，多种细菌元素参与了细菌的致病作用。本研究表明，牙龈卟啉卟啉分泌因子通过调节Wnt/β-catenin和希波- yap信号通路促进结直肠癌肿瘤进展。使用特异性抑制剂和牙龈卟啉卟啉突变菌株，我们的研究结果表明，半胱氨酸蛋白酶，特别是Lysin-gingipain （Kgp）和Argin-gingipain A (RgpA)，以及硫化氢（H₂S），强烈诱导上皮-间质转化（EMT）标志物的表达，导致细胞脱离和运动增加。这些发现揭示了微生物毒力和防御机制（如H₂S）与宿主细胞转化之间的新联系，提示细菌分泌因子在驱动结直肠癌瘤变中的潜在作用。
{"title":"Porphyromonas gingivalis secreted factors drive epithelial-mesenchymal transition (EMT) through gingipains and an H2S-mediated bacterial defense system.","authors":"Michal Kazelnik,Rana Masri,Michal Caspi,Amnon Wittenstein,Ilan Tsarfaty,Elhanan Borenstein,Tal Caller,Konstantin Shatalin,Evgeny Nudler,Rina Rosin-Arbesfeld","doi":"10.1080/19490976.2026.2647532","DOIUrl":"https://doi.org/10.1080/19490976.2026.2647532","url":null,"abstract":"Dysbiosis of the gut microbiota is strongly associated with a wide range of pathologies, including various types of cancer. Porphyromonas gingivalis (P. gingivalis), an oral bacterium, is implicated in the development of colorectal cancer (CRC), and although the exact mechanisms by which P. gingivalis contributes to CRC remain unclear, and emerging evidence suggests that various bacterial elements are involved in the bacterium's pathogenic effects. Here, we show that P. gingivalis secreted factors promote CRC neoplasia progression by modulating both the Wnt/β-catenin and the Hippo-YAP signaling pathways. Using specific inhibitors and P. gingivalis mutant strains, our findings demonstrate that cysteine proteases, specifically Lysin-gingipain (Kgp) and Argin-gingipain A (RgpA), as well as hydrogen sulfide (H₂S), strongly induce the expression of epithelial-mesenchymal transition (EMT) markers, leading to cell detachment and increased motility. These findings reveal a novel connection between microbial virulence and defense mechanisms, such as H₂S, and host cell transformation, suggesting a potential role for bacterial secreted factors in driving CRC neoplasia.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"24 1","pages":"2647532"},"PeriodicalIF":12.2,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502467","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}
Pub Date : 2026-03-23DOI: 10.1080/19490976.2026.2647591
Lisa Friess,Fionnuala M McAuliffe,Paul D Cotter,Anthony L Shiver,Kerwyn Casey Huang,Anne de Jong,Douwe van Sinderen
Plant-derived pentose sugars represent a major nutrient source in the gut, yet their metabolism remains incompletely defined. Strains of the human gut commensal Bifidobacterium longum subsp. longum utilise arabinose- and xylose-containing glycans, which are found in the pectin and hemicellulose layers of plant cell walls. To gain insight into the metabolism of these two pentoses as well as ribose, a naturally occurring sugar and a component of RNA and ATP, we identified and analysed the genes responsible for their uptake and subsequent catabolism. Based on transcriptomic data and mutant phenotype analyses, we show that these three pentoses share a common, ABC-type uptake system encoded by penABCD. Furthermore, we identify a gene cluster, araBDA, and two genes, xylA and xylB, that are required for conversion of arabinose and xylose, respectively, into xylulose-5-phosphate, and rbsK, which converts ribose into ribose-5-phosphate. These intermediate metabolic products enter the bifid shunt, an energy-generating fermentative pathway typical of bifidobacteria. We also show that arabinose and xylose are co-metabolized, while xylose is preferentially utilised before ribose. This study provides molecular insights using a multi-omics approach, including comparative genomics and transcriptomics combined with mutational analysis, into how B. longum subsp. longum metabolizes pentose-containing plant glycans, common yet indigestible components of the adult human diet.
{"title":"Metabolic pathway analysis reveals hierarchical pentose sugar utilization and metabolic flexibility of Bifidobacterium longum.","authors":"Lisa Friess,Fionnuala M McAuliffe,Paul D Cotter,Anthony L Shiver,Kerwyn Casey Huang,Anne de Jong,Douwe van Sinderen","doi":"10.1080/19490976.2026.2647591","DOIUrl":"https://doi.org/10.1080/19490976.2026.2647591","url":null,"abstract":"Plant-derived pentose sugars represent a major nutrient source in the gut, yet their metabolism remains incompletely defined. Strains of the human gut commensal Bifidobacterium longum subsp. longum utilise arabinose- and xylose-containing glycans, which are found in the pectin and hemicellulose layers of plant cell walls. To gain insight into the metabolism of these two pentoses as well as ribose, a naturally occurring sugar and a component of RNA and ATP, we identified and analysed the genes responsible for their uptake and subsequent catabolism. Based on transcriptomic data and mutant phenotype analyses, we show that these three pentoses share a common, ABC-type uptake system encoded by penABCD. Furthermore, we identify a gene cluster, araBDA, and two genes, xylA and xylB, that are required for conversion of arabinose and xylose, respectively, into xylulose-5-phosphate, and rbsK, which converts ribose into ribose-5-phosphate. These intermediate metabolic products enter the bifid shunt, an energy-generating fermentative pathway typical of bifidobacteria. We also show that arabinose and xylose are co-metabolized, while xylose is preferentially utilised before ribose. This study provides molecular insights using a multi-omics approach, including comparative genomics and transcriptomics combined with mutational analysis, into how B. longum subsp. longum metabolizes pentose-containing plant glycans, common yet indigestible components of the adult human diet.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"59 1","pages":"2647591"},"PeriodicalIF":12.2,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502506","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}
Degradation of mucins at the host-microbial mucus interphase involves glycosidases that release monosaccharides from O-glycans and mucinases that cleave the mucin protein backbone. Mucinases recognize and cleave peptide bonds at specific sequence motifs with varying O-glycan structures required and/or permissible. Mucinases that digest mucins with intact O-glycans can potentially destroy the protective mucus, while mucinases that only digest mucins with partially degraded O-glycans may serve at a later stage of nutrient sourcing from mucins. Here, we discovered nine CBM-bearing M60-like mucinases across gut commensals and opportunists, including a conserved Bacteroides fragilis mucinase denoted HC11. We also investigated the previously described Bacteroides thetaiotaomicron mucinase BT4244, which together delineates two functional classes with distinct preferences: BT4244 for bis-Tn (GalNAcα1-O-Ser/Thr) and HC11 for bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycans. Both mucinases harbor carbohydrate-binding modules (CBM32) that bind their cognate O-glycan motifs and are required - together with the catalytic domains - for efficient cleavage of extended mucin domains, which is consistent with cooperative engagement, but are not required for the cleavage of short glycopeptides. We show B. fragilis strains secrete HC11 and degrade mucins only after the removal of sialic acids. Together, these findings expand the mucinase repertoire by nine enzymes spanning commensals and opportunists, demonstrate that CBM32 domains are essential for efficient cleavage of extended mucin substrates likely by promoting multivalent engagement and substrate positioning, and nominateidentify CBM-catalytic cooperation as a mechanism and intervention point for controlling mucus turnover and barrier integrity.
黏液蛋白在宿主-微生物黏液间期的降解包括从o -聚糖中释放单糖的糖苷酶和切割黏液蛋白主干的黏液酶。粘酶识别和切割特定序列基序上的肽键，这些基序具有所需和/或允许的不同的o -聚糖结构。用完整的o -聚糖消化粘蛋白的粘酶可能潜在地破坏保护性粘液，而仅用部分降解的o -聚糖消化粘蛋白的粘酶可能在粘蛋白的营养来源的后期阶段发挥作用。在这里，我们在肠道共生菌和机会菌中发现了9种携带cbm的m60样黏酶，包括一种保守的脆弱拟杆菌黏酶HC11。我们还研究了先前描述的拟杆菌（Bacteroides thetaiotaomicron）粘酶BT4244，它共同描述了两个具有不同偏好的功能类别：BT4244用于双- tn （GalNAcα1-O-Ser/Thr）和HC11用于双- t (Galβ1-3GalNAcα1-O-Ser/Thr) o -聚糖。这两种粘酶都含有碳水化合物结合模块（CBM32），可以结合其同源的o -聚糖基序，并且需要与催化结构域一起有效地切割延伸的粘蛋白结构域，这与协同作用是一致的，但不需要切割短的糖肽。我们发现脆弱B.菌株只有在去除唾液酸后才会分泌HC11并降解粘蛋白。综上所述，这些发现扩大了黏液酶的种类，包括9种共生酶和机会酶，表明CBM32结构域可能通过促进多价接合和底物定位，对扩展黏液底物的有效切割至关重要，并提出了cbm催化合作作为控制黏液转换和屏障完整性的机制和干预点。
{"title":"Discovery of a secreted Bacteroides fragilis mucinase that cleaves mucins with bis-T O-glycans through a carbohydrate binding module-dependent mechanism.","authors":"Yoshiki Narimatsu,Cayetano Pleguezuelos-Manzano,Daniel Hornikx,Felix Goerdeler,Thapakorn Jaroentomeechai,Katia Flores,Sanae Narimatsu,Charelle Boot,Lars Hansen,Fabien Durbesson,Renaud Vincentelli,Laurie Comstock,Hans Clevers,Victor Taleb,Francisco Corzana,Bernard Henrissat,Henrik Clausen,Ramon Hurtado-Guerrero,Christian Büll","doi":"10.1080/19490976.2026.2644983","DOIUrl":"https://doi.org/10.1080/19490976.2026.2644983","url":null,"abstract":"Degradation of mucins at the host-microbial mucus interphase involves glycosidases that release monosaccharides from O-glycans and mucinases that cleave the mucin protein backbone. Mucinases recognize and cleave peptide bonds at specific sequence motifs with varying O-glycan structures required and/or permissible. Mucinases that digest mucins with intact O-glycans can potentially destroy the protective mucus, while mucinases that only digest mucins with partially degraded O-glycans may serve at a later stage of nutrient sourcing from mucins. Here, we discovered nine CBM-bearing M60-like mucinases across gut commensals and opportunists, including a conserved Bacteroides fragilis mucinase denoted HC11. We also investigated the previously described Bacteroides thetaiotaomicron mucinase BT4244, which together delineates two functional classes with distinct preferences: BT4244 for bis-Tn (GalNAcα1-O-Ser/Thr) and HC11 for bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycans. Both mucinases harbor carbohydrate-binding modules (CBM32) that bind their cognate O-glycan motifs and are required - together with the catalytic domains - for efficient cleavage of extended mucin domains, which is consistent with cooperative engagement, but are not required for the cleavage of short glycopeptides. We show B. fragilis strains secrete HC11 and degrade mucins only after the removal of sialic acids. Together, these findings expand the mucinase repertoire by nine enzymes spanning commensals and opportunists, demonstrate that CBM32 domains are essential for efficient cleavage of extended mucin substrates likely by promoting multivalent engagement and substrate positioning, and nominateidentify CBM-catalytic cooperation as a mechanism and intervention point for controlling mucus turnover and barrier integrity.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"8 1","pages":"2644983"},"PeriodicalIF":12.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483639","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}
Intestinal fibrosis is a severe complication of Crohn's disease for which therapy remains suboptimal. Probiotics are widely used in the treatment of intestinal inflammation, but all major guidelines do not recommend in favor of their use, with the exception of an 8-strains bacterial formula, which is recommended for the treatment of pouch inflammation in ulcerative colitis. Using this 8-strains formulation as a comparator, we characterized a 9-strains probiotic formulation enriched with Lactobacillus rhamnosus and paracasei in a mouse model of intestinal inflammation and fibrosis. Our findings demonstrated that while both formulations exerted similar protective effects in acute colitis, only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis. Mechanistically, we found that the 9-strains formulation remodeled the microbiota composition and the structure of microbiota-derived secondary bile acids, leading to the selective enrichment of those bile acids that act as GPBAR1 agonists, including 3-oxo-DCA, which in vitro directly attenuates activation of intestinal fibroblasts. Confirming the role of this pathway, feeding Gpbar1⁻/⁻ mice with 9-strains probiotic formulation abrogates its beneficial effects on inflammation and fibrosis. These findings highlight the importance of microbial metabolites in shaping probiotic efficacy and support the development of probiotic formulations that target host-microbiota interactions through bile acid signaling.
{"title":"A bile acid-GPBAR1 network supports anti-inflammatory and anti-fibrotic benefits of probiotics in colitis.","authors":"Michele Biagioli,Cristina Di Giorgio,Silvia Marchianò,Benedetta Sensini,Ginevra Urbani,Eleonora Giannelli,Ginevra Lachi,Carmen Massa,Maria Rosaria Sette,Francesca Paniconi,Elva Morretta,Maria Chiara Monti,Angela Zampella,Eleonora Distrutti,Stefano Fiorucci","doi":"10.1080/19490976.2026.2645125","DOIUrl":"https://doi.org/10.1080/19490976.2026.2645125","url":null,"abstract":"Intestinal fibrosis is a severe complication of Crohn's disease for which therapy remains suboptimal. Probiotics are widely used in the treatment of intestinal inflammation, but all major guidelines do not recommend in favor of their use, with the exception of an 8-strains bacterial formula, which is recommended for the treatment of pouch inflammation in ulcerative colitis. Using this 8-strains formulation as a comparator, we characterized a 9-strains probiotic formulation enriched with Lactobacillus rhamnosus and paracasei in a mouse model of intestinal inflammation and fibrosis. Our findings demonstrated that while both formulations exerted similar protective effects in acute colitis, only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis. Mechanistically, we found that the 9-strains formulation remodeled the microbiota composition and the structure of microbiota-derived secondary bile acids, leading to the selective enrichment of those bile acids that act as GPBAR1 agonists, including 3-oxo-DCA, which in vitro directly attenuates activation of intestinal fibroblasts. Confirming the role of this pathway, feeding Gpbar1⁻/⁻ mice with 9-strains probiotic formulation abrogates its beneficial effects on inflammation and fibrosis. These findings highlight the importance of microbial metabolites in shaping probiotic efficacy and support the development of probiotic formulations that target host-microbiota interactions through bile acid signaling.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"83 1","pages":"2645125"},"PeriodicalIF":12.2,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478593","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}
Pub Date : 2026-03-18DOI: 10.1080/19490976.2026.2644684
Raphael R Fagundes,Sean P Colgan
Indigestible dietary fibers shape intestinal mucosal physiology, yet the mechanisms linking fiber-derived microbial activity to epithelial remodeling remain incompletely understood. In their recent study, Ribeiro Castro et al. revealed that the prebiotic inulin induces reprogramming of intestinal epithelial metabolism and proliferation through microbiota-dependent hypoxia and epithelial HIF1α activation. In this commentary, we discuss their findings and highlight the emerging concept that microbial fermentation and oxygen concentrations act as structured physiological signals that guide intestinal epithelial differentiation and crypt-villus dynamics. We further explore how these findings intersect with prior work on SCFA metabolism, butyrate-mediated ISC inhibition, and fructose-driven epithelial growth, and we discuss open questions regarding downstream HIF1α programs, niche accessibility, and immune‒epithelial crosstalk. Understanding how HIF1α calibrates this balance will be essential for safely leveraging prebiotics and microbiome-targeted interventions that promote mucosal health.
{"title":"Feeding microbes to feed the Gut: inulin reprograms intestinal epithelial metabolism and proliferation through HIF1α.","authors":"Raphael R Fagundes,Sean P Colgan","doi":"10.1080/19490976.2026.2644684","DOIUrl":"https://doi.org/10.1080/19490976.2026.2644684","url":null,"abstract":"Indigestible dietary fibers shape intestinal mucosal physiology, yet the mechanisms linking fiber-derived microbial activity to epithelial remodeling remain incompletely understood. In their recent study, Ribeiro Castro et al. revealed that the prebiotic inulin induces reprogramming of intestinal epithelial metabolism and proliferation through microbiota-dependent hypoxia and epithelial HIF1α activation. In this commentary, we discuss their findings and highlight the emerging concept that microbial fermentation and oxygen concentrations act as structured physiological signals that guide intestinal epithelial differentiation and crypt-villus dynamics. We further explore how these findings intersect with prior work on SCFA metabolism, butyrate-mediated ISC inhibition, and fructose-driven epithelial growth, and we discuss open questions regarding downstream HIF1α programs, niche accessibility, and immune‒epithelial crosstalk. Understanding how HIF1α calibrates this balance will be essential for safely leveraging prebiotics and microbiome-targeted interventions that promote mucosal health.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"12 1","pages":"2644684"},"PeriodicalIF":12.2,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478594","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}
Pub Date : 2026-03-17DOI: 10.1080/19490976.2026.2645267
Jerry Elorm Akresi, Thi Van Thanh Do, Zhisong Cui, N. R. Siva Shanmugam, Sarah Moraïs, Itzhak Mizrahi, Edward A. Bayer, Jennifer M. Auchtung, Yanbin Yin
{"title":"Limousia bacteria encode mucinolysome for mucin utilization in animal gut microbiomes","authors":"Jerry Elorm Akresi, Thi Van Thanh Do, Zhisong Cui, N. R. Siva Shanmugam, Sarah Moraïs, Itzhak Mizrahi, Edward A. Bayer, Jennifer M. Auchtung, Yanbin Yin","doi":"10.1080/19490976.2026.2645267","DOIUrl":"https://doi.org/10.1080/19490976.2026.2645267","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"13 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465184","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}
Alterations in the composition and function of the gut microbiome are important in obesity and type 2 diabetes development. Using our cross-sectional FoCus cohort, we recently found Parasutterella species were increased in human obesity and type 2 diabetes and linked to abnormalities in triglyceride metabolism and L-cysteine homeostasis, the latter being important for beta-cell function. To gain further insights, we now quantified gut Parasutterella excrementihominis by qPCR in n = 215 human subjects during an interdisciplinary non-surgical obesity therapy program consisting of an initial weight-reduction phase (weeks 1-12) followed by a weight-maintenance phase (weeks 13-26). P. excrementihominis abundance was significantly reduced during the weight reduction phase. While baseline abundance levels did not predict the success of weight-reduction, they were inversely associated with C-reactive-protein improvements. Interestingly, the decrease in P. excrementihominis abundance during the weight reduction phase was positively correlated with improvements in insulin sensitivity throughout the overall obesity intervention. Regarding the weight maintenance phase, a re-increase of P. excrementihominis abundance was significantly associated with weight regain. In summary, our data suggest that P. excrementihominis attenuates metabolic and inflammatory improvements in obese human subjects under therapy and highlight a potential role of this bacterial species in metabolic adaptation during weight loss interventions.
{"title":"Parasutterella excrementihominis is associated with attenuated metabolic improvements during obesity therapy in humans.","authors":"Shuo Liu,Kristina Schlicht,Alexia Beckmann,Katharina Hartmann,Weixiao Wang,Lucy Kruse,Perdita Wietzke-Braun,Tim Hollstein,Ulla Becker,Ursula Ziegenbruch,Frauke Baumgartner,Wiebke Diederich,Amelie Laudes,Janne Muchaier,Mareike Stobbe,Lea Homeister,Sophia Remy,Nele Dornstauder,Maja Vogel,Carl Schindler,Kathrin Türk,Corinna Geisler,Nathalie Rohmann,Matthias Laudes","doi":"10.1080/19490976.2026.2644687","DOIUrl":"https://doi.org/10.1080/19490976.2026.2644687","url":null,"abstract":"Alterations in the composition and function of the gut microbiome are important in obesity and type 2 diabetes development. Using our cross-sectional FoCus cohort, we recently found Parasutterella species were increased in human obesity and type 2 diabetes and linked to abnormalities in triglyceride metabolism and L-cysteine homeostasis, the latter being important for beta-cell function. To gain further insights, we now quantified gut Parasutterella excrementihominis by qPCR in n = 215 human subjects during an interdisciplinary non-surgical obesity therapy program consisting of an initial weight-reduction phase (weeks 1-12) followed by a weight-maintenance phase (weeks 13-26). P. excrementihominis abundance was significantly reduced during the weight reduction phase. While baseline abundance levels did not predict the success of weight-reduction, they were inversely associated with C-reactive-protein improvements. Interestingly, the decrease in P. excrementihominis abundance during the weight reduction phase was positively correlated with improvements in insulin sensitivity throughout the overall obesity intervention. Regarding the weight maintenance phase, a re-increase of P. excrementihominis abundance was significantly associated with weight regain. In summary, our data suggest that P. excrementihominis attenuates metabolic and inflammatory improvements in obese human subjects under therapy and highlight a potential role of this bacterial species in metabolic adaptation during weight loss interventions.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"20 1","pages":"2644687"},"PeriodicalIF":12.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471436","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}
Pub Date : 2026-03-17DOI: 10.1080/19490976.2026.2644682
Yu Zhang,Dong D Wang
Type 2 diabetes (T2D) is a heterogeneous metabolic disorder in which environmental exposures interact with host biology to drive insulin resistance and progressive β-cell dysfunction. This review synthesizes recent advances showing how the gut microbiome mediates these processes across multiple levels of resolution. First, large-scale shotgun metagenomic studies consistently identify a reproducible T2D-associated signature characterized by depletion of short-chain fatty acid-producing taxa and enrichment of opportunistic, pro-inflammatory microorganisms, while highlighting the importance of controlling for major confounders such as adiposity and glucose-lowering medications. Second, functional profiling and metabolomics link microbial community shifts to coordinated pathway changes-including reduced short-chain fatty acid and secondary bile acid production and increased endotoxin- and branched-chain amino acid-related metabolism-that influence gut barrier integrity, inflammatory tone, insulin sensitivity, and pancreatic β-cell function. Third, we discuss how integrative multi-omics (metagenomics, metatranscriptomics, proteomics, and metabolomics) can connect microbial genetic potential to in vivo activity and circulating metabolites, while introducing key challenges such as temporal variability, anatomical heterogeneity, and "dark matter" in gene and metabolite annotation. Fourth, strain-resolved analyses reveal that many disease-associated functions are carried by specific lineages within species, refining microbial targets and helping explain inconsistent species-level associations. Fifth, we summarize how diet shapes microbial ecology and function-supporting microbiome-informed precision nutrition-and highlight emerging evidence beyond bacteria, including viral and fungal community components. Finally, we outline translational opportunities and evidence gaps, emphasizing the need for diverse longitudinal cohorts, mechanistic validation, and well-controlled interventional trials to evaluate microbiome-directed strategies for T2D prevention and treatment.
{"title":"Gut microbiome in type 2 diabetes: insights from metagenomics, multi-omics, and diet-microbe interactions.","authors":"Yu Zhang,Dong D Wang","doi":"10.1080/19490976.2026.2644682","DOIUrl":"https://doi.org/10.1080/19490976.2026.2644682","url":null,"abstract":"Type 2 diabetes (T2D) is a heterogeneous metabolic disorder in which environmental exposures interact with host biology to drive insulin resistance and progressive β-cell dysfunction. This review synthesizes recent advances showing how the gut microbiome mediates these processes across multiple levels of resolution. First, large-scale shotgun metagenomic studies consistently identify a reproducible T2D-associated signature characterized by depletion of short-chain fatty acid-producing taxa and enrichment of opportunistic, pro-inflammatory microorganisms, while highlighting the importance of controlling for major confounders such as adiposity and glucose-lowering medications. Second, functional profiling and metabolomics link microbial community shifts to coordinated pathway changes-including reduced short-chain fatty acid and secondary bile acid production and increased endotoxin- and branched-chain amino acid-related metabolism-that influence gut barrier integrity, inflammatory tone, insulin sensitivity, and pancreatic β-cell function. Third, we discuss how integrative multi-omics (metagenomics, metatranscriptomics, proteomics, and metabolomics) can connect microbial genetic potential to in vivo activity and circulating metabolites, while introducing key challenges such as temporal variability, anatomical heterogeneity, and \"dark matter\" in gene and metabolite annotation. Fourth, strain-resolved analyses reveal that many disease-associated functions are carried by specific lineages within species, refining microbial targets and helping explain inconsistent species-level associations. Fifth, we summarize how diet shapes microbial ecology and function-supporting microbiome-informed precision nutrition-and highlight emerging evidence beyond bacteria, including viral and fungal community components. Finally, we outline translational opportunities and evidence gaps, emphasizing the need for diverse longitudinal cohorts, mechanistic validation, and well-controlled interventional trials to evaluate microbiome-directed strategies for T2D prevention and treatment.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"11 1","pages":"2644682"},"PeriodicalIF":12.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471433","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}
Pub Date : 2026-03-17DOI: 10.1080/19490976.2026.2643373
Yahya Jama,Waliul Khan,Stephen M Collins
Early childhood malnutrition (ECM) is robustly associated with increased risk of cognitive impairment and neuropsychiatric disorders across the lifespan, yet the biological mechanisms underlying this vulnerability remain incompletely defined. Accumulating clinical evidence indicates that ECM is associated with delayed maturation and reduced diversity of the intestinal microbiota, including depletion of taxa involved in short-chain fatty acid production and complex carbohydrate fermentation. These microbial alterations coincide with broader metabolic, immune, and barrier dysfunctions - such as reduced availability of neuroactive metabolites, low-grade inflammation, and impaired intestinal and vascular integrity - that plausibly intersect with critical processes in brain development. Experimental studies in animal models demonstrate that perturbation of microbiota-derived signaling during sensitive early periods is sufficient to induce lasting neurodevelopmental and behavioral changes, providing proof of concept for a causal role. However, in human populations, the microbiota remains best viewed as a biologically plausible intermediary rather than a proven determinant of outcome. Future progress will require integrative longitudinal studies and developmentally timed interventions to test whether restoration of microbiota function can modify neurodevelopmental trajectories. Clarifying these relationships has important implications for understanding the long-term consequences of early nutritional adversity and for identifying preventive strategies in settings where ECM remains prevalent.
{"title":"The putative role of the microbiota in the development of neuropsychiatric disorders following early childhood malnutrition.","authors":"Yahya Jama,Waliul Khan,Stephen M Collins","doi":"10.1080/19490976.2026.2643373","DOIUrl":"https://doi.org/10.1080/19490976.2026.2643373","url":null,"abstract":"Early childhood malnutrition (ECM) is robustly associated with increased risk of cognitive impairment and neuropsychiatric disorders across the lifespan, yet the biological mechanisms underlying this vulnerability remain incompletely defined. Accumulating clinical evidence indicates that ECM is associated with delayed maturation and reduced diversity of the intestinal microbiota, including depletion of taxa involved in short-chain fatty acid production and complex carbohydrate fermentation. These microbial alterations coincide with broader metabolic, immune, and barrier dysfunctions - such as reduced availability of neuroactive metabolites, low-grade inflammation, and impaired intestinal and vascular integrity - that plausibly intersect with critical processes in brain development. Experimental studies in animal models demonstrate that perturbation of microbiota-derived signaling during sensitive early periods is sufficient to induce lasting neurodevelopmental and behavioral changes, providing proof of concept for a causal role. However, in human populations, the microbiota remains best viewed as a biologically plausible intermediary rather than a proven determinant of outcome. Future progress will require integrative longitudinal studies and developmentally timed interventions to test whether restoration of microbiota function can modify neurodevelopmental trajectories. Clarifying these relationships has important implications for understanding the long-term consequences of early nutritional adversity and for identifying preventive strategies in settings where ECM remains prevalent.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"1 1","pages":"2643373"},"PeriodicalIF":12.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471432","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}
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