{"title":"The gut virome and regulatory T cell axis in health and systemic disease.","authors":"Dandan Bi, Shaochen Yu, Mengjie Zhang, Yuting Huang, Ziyue Dou, Beibei Tian, Jian Lu","doi":"10.20517/mrr.2026.20","DOIUrl":"10.20517/mrr.2026.20","url":null,"abstract":"<p><p>The gut virome, comprising bacteriophages and eukaryotic viruses, represents a complex and dynamic component of the intestinal microbiome whose functional significance has long been underestimated. Emerging evidence highlights the gut virome as a pivotal modulator of the host immune system, particularly in regulating the balance and function of regulatory T cells (Tregs), which are essential for maintaining immune homeostasis. This review distinguishes two mechanistic axes by which the virome influences Tregs: (i) an indirect 'virome-bacteriome-metabolite-Treg axis', and (ii) a direct 'viral pathogen-associated molecular patterns (PAMPs)-pattern recognition receptors (PRRs)-Treg' signaling axis. This review comprehensively examines the dualistic role of the gut virome in preserving intestinal equilibrium and its involvement in the pathogenesis or amelioration of intestinal inflammatory disorders such as inflammatory bowel disease (IBD). Furthermore, the influence of the gut virome extends beyond the gut, potentially impacting systemic immune-related diseases. By integrating recent advances in metagenomics, viromics, and immunology, we elucidate the molecular mechanisms through which the gut virome orchestrates immune regulation. This synthesis aims to provide a comprehensive understanding of the gut virome as a critical immune regulator and to explore its potential as a biomarker for disease diagnosis and a novel target for therapeutic intervention.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"14"},"PeriodicalIF":5.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexa R Gormley, Yesid Garavito-Duarte, Jeonghyeon Son, Sung Woo Kim
{"title":"Intestinal microbiota in nursery pigs: comments on anatomical location, spatial niches, and approaches to data interpretation.","authors":"Alexa R Gormley, Yesid Garavito-Duarte, Jeonghyeon Son, Sung Woo Kim","doi":"10.20517/mrr.2026.21","DOIUrl":"10.20517/mrr.2026.21","url":null,"abstract":"","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"13"},"PeriodicalIF":5.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic potential of <i>Lachnospiraceae</i> strains in irritable bowel syndrome via differential gut-brain pathways.","authors":"Wanyu Yang, Shuigen Bian, Huizi Tan","doi":"10.20517/mrr.2026.08","DOIUrl":"10.20517/mrr.2026.08","url":null,"abstract":"<p><p><b>Background:</b> Irritable bowel syndrome (IBS) is a highly prevalent disorder that significantly impairs quality of life, yet effective treatments remain limited. While prior work from our laboratory linked the <i>Lachnospiraceae</i> family to IBS severity, conflicting sequencing data necessitated a deeper investigation into this taxonomic group. <b>Methods:</b> We evaluated the therapeutic potential of four representative <i>Lachnospiraceae</i> strains in IBS mice with standardized gut microbiota baseline (SynCom-23). Core symptoms were assessed via body weight, fecal status, and visceral hypersensitivity. Intestinal inflammation, oxidative stress, and barrier function were evaluated by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT-qPCR), and gut microbiota and metabolites were analyzed by 16S rRNA sequencing, gas chromatography-flame ionization detector (GC-FID), and liquid chromatography-mass spectrometry (LC-MS), together with brain neurotransmitter systems. <b>Results:</b> We found that all four strains effectively alleviated IBS symptoms, reducing weight loss (<i>P</i> < 0.001) and visceral hypersensitivity markers calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) (<i>P</i> < 0.0001), potentially through distinct pathways: <i>Blautia wexlerae</i> MW-022 produces substantial acetic acid, stimulates <i>Lactobacillaceae</i> proliferation, and targets the γ-aminobutyric acid/glutamate (GABA/Glu) system. <i>Roseburia faecis</i> MW-024 produces butyrate, affecting the GABA/Glu system. <i>Dorea longicatena</i> MW-023 enhances the serotonin (5-HT) system at synthesis and reception levels; and <i>Coprococcus eutactus</i> DSM107541 modulates the 5-HT system via the \"clearance-reception\" mode. Combined strains achieved more comprehensive gut micro-ecology restoration. <b>Conclusion:</b> This study systematically elucidates the heterogeneity in the mechanisms by which <i>Lachnospiraceae</i> strains treat IBS at the strain level. Different strains achieve precise regulation through their specific gut-brain axes. These findings offer strain-level insights and a foundation for developing <i>Lachnospiraceae</i>-based microbial therapies.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"12"},"PeriodicalIF":5.2,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evangelia N Kerezoudi, Sue McKay, Seta Kurt, Maaike De Kreek, Jelle De Medts, Lynn Verstrepen, Jonas Ghyselinck, Lieven Van Meulebroek, Wim Calame, Ruud Albers, Annick Mercenier, Robert J Brummer, Ignacio Rangel
{"title":"Dietary chicory rhamnogalacturonan-I modulates gut microbiota and immune responses in healthy adults.","authors":"Evangelia N Kerezoudi, Sue McKay, Seta Kurt, Maaike De Kreek, Jelle De Medts, Lynn Verstrepen, Jonas Ghyselinck, Lieven Van Meulebroek, Wim Calame, Ruud Albers, Annick Mercenier, Robert J Brummer, Ignacio Rangel","doi":"10.20517/mrr.2026.04","DOIUrl":"10.20517/mrr.2026.04","url":null,"abstract":"<p><p><b>Background:</b> Pectic rhamnogalacturonan-I (RG-I) is a dietary fiber that modulates the gut-immune axis. This study evaluates a novel variant of RG-I from chicory root (chRG-I). <b>Methods:</b> In a randomized, double-blind, placebo-controlled trial, 55 healthy adults were stratified by habitual fiber intake and baseline <i>Bifidobacterium</i> levels before receiving 500 mg/day of chRG-I or placebo for four weeks. Primary endpoints included fecal <i>Bifidobacterium</i> counts. Secondary outcomes assessed fecal metabolites, systemic immune cell activation markers, and gastrointestinal symptoms. To provide mechanistic insights, donor-matched fecal samples were used in <i>in vitro</i> fermentation and Caco-2/peripheral blood mononuclear cell co-culture gut barrier models. <b>Results:</b> Supplementation with chRG-I induced a statistically significant bifidogenic effect, with absolute levels peaking at week three, and lower levels of some fecal short-chain fatty acids (SCFA) compared to placebo. However, donor-matched <i>in vitro</i> fermentations with chRG-I confirmed robust production of SCFA and reduction of branched-chain fatty acids levels (BCFA). Systemically, chRG-I upregulated HLA-DR expression on myeloid dendritic cells. Clinically, chRG-I was well-tolerated and slightly improved stool consistency compared to placebo. In an intestinal barrier challenge model, chRG-I fermentates (a pool of metabolites including SCFA and fragments of chRG-I) protected barrier integrity, modulated the cytokine milieu away from a predominantly pro-inflammatory response, as characterized by increased IL4 and IL22 and reduced IL9, IL17A, and IL21. <b>Conclusion:</b> Supplementation with a low dose of chRG-I is well-tolerated, beneficially modulates the gut microbiome - which can protect the intestinal barrier, and subtly enhances systemic immune readiness, suggesting that chRG-I may have benefits as a functional food ingredient.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"11"},"PeriodicalIF":5.2,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mapping the genomic landscape of two key human gut microbial species: <i>Bifidobacterium infantis</i> and <i>Bifidobacterium longum</i>.","authors":"Marco Ventura","doi":"10.20517/mrr.2026.15","DOIUrl":"10.20517/mrr.2026.15","url":null,"abstract":"","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"10"},"PeriodicalIF":5.2,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taylor D Ticer, Pramita Suresh, Subhomitra Ghoshal, Anna M Tingler, Rachel Stubler, Adelaide E Horvath, Janiece S Glover, Terri N Ellis, Melinda A Engevik
{"title":"Intestinal mucus acts as a nutrient source and signal for <i>Klebsiella pneumoniae</i>.","authors":"Taylor D Ticer, Pramita Suresh, Subhomitra Ghoshal, Anna M Tingler, Rachel Stubler, Adelaide E Horvath, Janiece S Glover, Terri N Ellis, Melinda A Engevik","doi":"10.20517/mrr.2025.112","DOIUrl":"10.20517/mrr.2025.112","url":null,"abstract":"<p><p><b>Background:</b> <i>Klebsiella pneumoniae</i> can colonize the gastrointestinal tract, yet its interactions with intestinal mucus remain poorly defined. In this study, we examined the capacity of <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) to adhere and use intestinal mucus and its associated glycans. <b>Methods:</b> Multiple commercial and clinical <i>K. pneumoniae</i> isolates were tested for adhesion to porcine and human Mucin 2 (MUC2) using fluorescence-based assays and microscopy. <i>In vivo</i> mucus localization was examined in colonized mice by fluorescent <i>in situ</i> hybridization (FISH). Genomic analyses of <i>K. pneumoniae</i> genomes were performed to identify glycosyl hydrolases and sugar utilization pathways. Growth on mucin-derived monosaccharides or intact mucus was assessed in minimal media. Biofilm formation and aminoglycoside susceptibility were measured in the presence or absence of mucus. <b>Results:</b> All <i>K. pneumoniae</i> strains adhered robustly to porcine and human MUC2 <i>in vitro</i> and we found <i>K. pneumoniae</i> localized to the murine mucus layer <i>in vivo</i>. Genomic analysis of over 1,000 <i>K. pneumoniae</i> isolates revealed that most strains possess glycosyl hydrolases targeting internal galactose, N-acetyl-glucosamine (GlcNAc), and N-acetyl-galactosamine (GalNAc) glycan sugars, though they lack enzymes to cleave terminal fucose or N-acetyl-neuraminic acid. Consistent with this finding, we found that <i>K. pneumoniae</i> alone could not grow in minimal media with intact mucus as a sole carbon source. However, we found that <i>K. pneumoniae</i> could grow with free mucus glycan-derived sugars galactose, GlcNAc, GalNAc fucose and N-acetyl-neuraminic acid. Mucus did not alter biofilm formation, but it significantly increased sensitivity to gentamicin, kanamycin and streptomycin. <b>Conclusion:</b> These findings identify mucus as an important modulator of <i>K. pneumoniae</i> colonization and antibiotic responsiveness.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"9"},"PeriodicalIF":5.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shahna Fathima, Tina Sarkar, Navneet Sharma, Paul E Kilgore, Huan H Nguyen
{"title":"Immunoglobulin Y protects intestinal epithelium and modulates gut microbiota.","authors":"Shahna Fathima, Tina Sarkar, Navneet Sharma, Paul E Kilgore, Huan H Nguyen","doi":"10.20517/mrr.2025.104","DOIUrl":"10.20517/mrr.2025.104","url":null,"abstract":"<p><p><b>Aim:</b> This study investigated the effects of Muno-IgY®, a multi-pathogen-specific immunoglobulin Y (IgY), on microbial growth, adhesion, fermentation activity, and immune signaling using a multi-tiered <i>in vitro</i> approach. <b>Methods:</b> IgY activity was first evaluated in Caco-2 adhesion and invasion assays using adherent-invasive <i>Escherichia coli</i> (AIEC) at optimized concentrations, followed by assessment in a SHIME® <i>in vitro</i> gut model inoculated with human fecal microbiota enriched in Enterobacteriaceae. Microbial composition, fermentation markers, and metabolite production were analyzed, and downstream effects on epithelial barrier integrity and immune signaling were evaluated using a Caco-2/peripheral blood mononuclear cell (PBMC) co-culture model exposed to SHIME® effluents. <b>Results:</b> Muno-IgY® significantly reduced AIEC adhesion/invasion from 39.76% in controls to 13.08% and 9.13% at 3 and 6 mg/mL, respectively (<i>P</i> < 0.05). In the SHIME® model, IgY significantly increased acetate and propionate production (<i>P</i> < 0.05), alongside a marked increase in ammonium concentration (<i>P</i> < 0.01). Microbial biomass increased modestly, while alpha- and beta-diversity indices were not significantly altered. The compositional shifts indicated enrichment of beneficial and mucin-associated taxa and reduction of opportunistic or pathogenic species in the Muno-IgY® group. In Caco-2/PBMC co-cultures, IgY-treated effluent decreased transepithelial electrical resistance (TEER) indicating reduced barrier integrity (<i>P</i> < 0.05) but significantly decreased pro-inflammatory cytokines Interferon-γ (IFN-γ) and Interleukin-22 (IL-22) (<i>P</i> < 0.05). <b>Conclusions:</b> Muno-IgY® demonstrates the ability to inhibit pathogen adhesion and modulate microbial composition and immune responses <i>in vitro</i>. These findings support its potential as a non-antibiotic approach for microbiome-targeted interventions, although further validation <i>in vivo</i> is required.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 2","pages":"8"},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a multi-targeted metabolomics platform for semi-quantification of faecal metabolites: a proof-of-concept analysis in human faeces.","authors":"Kayo Ikuta, Akihiro Kunisawa, Itaru Dekio, Arisa Ito, Qiuyi Wang, Kazuhiro Kawamura, Masaki Yamada, Sumi Nakamura, Yoshihiro Hayakawa, Takuma Higurashi, Junko Iida, Eiichiro Fukusaki, Toru Suzuki, Mitsuharu Matsumoto","doi":"10.20517/mrr.2025.85","DOIUrl":"10.20517/mrr.2025.85","url":null,"abstract":"<p><p><b>Objectives:</b> Targeted metabolomic analysis of faecal samples has been limited by narrow chemical coverage. Here, we established a multiplexed, triple quadrupole mass spectrometry (TQMS)-based targeted metabolomics workflow. This workflow allows accurate detection and semi-quantification of diverse faecal metabolites and provides a methodological platform for studying host-microbiome metabolic interactions. <b>Methods:</b> Faecal metabolomes from germ-free (GF) mice, ex-germ-free (Ex-GF) mice, and human participants were analysed using TQMS-based targeted metabolomics. The analysis comprised multiple methods targeting amino acids and their derivatives, carbohydrates, short-chain fatty acids, bile acids, lipid mediators, and phospholipids. <b>Results:</b> In total, 607 low-molecular-weight metabolites in 44 chemical categories were detected and semi-quantified. Faecal metabolomes of GF and Ex-GF mice were analysed, uncovering 341 intestinal microbiome-dependent metabolites. A proof-of-concept analysis using faecal samples from five patients with colorectal cancer demonstrated the successful application of this platform to human clinical material, highlighting its strong potential for future disease-oriented metabolomic investigations. <b>Conclusion:</b> We developed a multi-targeted faecal metabolomics platform that substantially expands the chemical space accessible to targeted analysis. This workflow provides a methodological foundation for future large-scale and translational studies.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 1","pages":"7"},"PeriodicalIF":5.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriele Andrea Lugli, Emanuele Selleri, Chiara Tarracchini, Aryanna Muscò, Silvia Petraro, Giulia Longhi, Leonardo Mancabelli, Christian Milani, Francesca Turroni, Marco Ventura
{"title":"Unveiling the genetic landscape and motility-associated functions of Type IV pili in the <i>Bifidobacterium</i> genus.","authors":"Gabriele Andrea Lugli, Emanuele Selleri, Chiara Tarracchini, Aryanna Muscò, Silvia Petraro, Giulia Longhi, Leonardo Mancabelli, Christian Milani, Francesca Turroni, Marco Ventura","doi":"10.20517/mrr.2025.119","DOIUrl":"10.20517/mrr.2025.119","url":null,"abstract":"<p><p><b>Background:</b> Bifidobacteria are recognized as one of the most influential bacterial groups inhabiting the human gut, capable of modulating the host's health. To understand how these bacteria interact with their hosts, it is essential to investigate their extracellular structures, such as pili. While the presence of sortase-dependent pili has already been investigated in the <i>Bifidobacterium</i> genus, limited information is available on Type IV pili (T4P), which have previously been identified in a few species as tight adherence (Tad) loci. <b>Methods:</b> Here, we explored the T4P distribution across the currently 117 (sub)species representing all described taxa of the <i>Bifidobacterium</i> genus, revealing two distinct loci unevenly distributed within the genus through <i>in silico</i> genomic analyses supported by <i>in vitro</i> validation. <b>Results:</b> Our analysis identified a conserved Type IVc pili (T4cP) structure across all bifidobacterial taxa, with minor predicted structural variations in members of the <i>Bifidobacterium longum</i> and <i>Bifidobacterium boum</i> phylogenetic groups. This T4cP structure, also known as Tad, exhibited an ancestral, non-retractile architecture typically associated with stable colonization and long-term persistence. In addition, a secondary Type IVa pili (T4aP) structure was detected in 13 bifidobacterial species. These species are associated with specific ecological niches, including primate, bovine, and porcine hosts, suggesting a link between this locus and host-associated adaptation. <b>Conclusion:</b> Notably, twitching motility assays demonstrated that <i>Bifidobacterium adolescentis</i> strains harboring the T4aP locus exhibit motility in response to specific environmental signals, observed upon starch supplementation of the growth medium, thereby challenging the traditional view of bifidobacteria as a strictly non-motile bacterial genus.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 1","pages":"6"},"PeriodicalIF":5.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simen Hyll Hansen, Niharika Bhattacharjee, Chang Hu, Maria Gjerstad Maseng, Olle Grannö, Corinna Bang, Christine Olbjørn, Gøri Perminow, Jørgen Valeur, May-Bente Bengtson, Svein Oskar Frigstad, Svend Andersen, Tone Bergene Aabrekk, Trond Espen Detlie, Andre Franke, Vendel A Kristensen, Jonas Halfvarson, Marte Lie Høivik, Ravishankar K Iyer, Johannes Hov
{"title":"Bacterial clusters are associated with the risk of severe disease progression in inflammatory bowel disease irrespective of conventional disease categories.","authors":"Simen Hyll Hansen, Niharika Bhattacharjee, Chang Hu, Maria Gjerstad Maseng, Olle Grannö, Corinna Bang, Christine Olbjørn, Gøri Perminow, Jørgen Valeur, May-Bente Bengtson, Svein Oskar Frigstad, Svend Andersen, Tone Bergene Aabrekk, Trond Espen Detlie, Andre Franke, Vendel A Kristensen, Jonas Halfvarson, Marte Lie Høivik, Ravishankar K Iyer, Johannes Hov","doi":"10.20517/mrr.2025.96","DOIUrl":"10.20517/mrr.2025.96","url":null,"abstract":"<p><p><b>Background:</b> Inflammatory bowel diseases (IBDs) are complex conditions marked by chronic inflammation in the gastrointestinal tract. Traditional classification separates IBD into Crohn's disease and ulcerative colitis, but this division may not fully capture disease heterogeneity. Here, we examine whether microbiome-driven subtyping can describe novel clinical IBD phenotypes. To achieve this, we applied unsupervised clustering to fecal microbiota profiles from the population-based Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) cohort. <b>Methods:</b> A Gaussian Mixture Model (GMM) was used to cluster participants with IBD based on microbiome composition and examine associations between clusters and clinical outcomes, including inflammatory markers and disease severity during the first year after inclusion. <b>Results:</b> Three microbiome-based clusters were identified: CLO (dominated by <i>Clostridia UCG-014</i>), ALF (<i>Agathobacter, Lachnoclostridium</i>, and <i>Faecalibacterium</i>), and RUM (<i>Ruminococcus gnavus</i>). Participants in the RUM cluster had a higher risk of future severe disease than those in the CLO cluster, even among participants with remission-to-mild disease at inclusion (21% <i>vs.</i> 6%, <i>P</i> < 0.00001). This association could not be explained by antibiotic use or baseline disease severity. Cluster membership alone performed comparably to fecal calprotectin in distinguishing severe disease, and a combined model significantly improved accuracy (<i>P</i> < 0.0001). <b>Conclusion:</b> Our findings demonstrate a connection between microbiome composition and the risk of severe disease development, which is partly independent of inflammation levels at the time of sampling. Microbiome-informed subgrouping could lead to more personalized treatment strategies. Further validation is needed to determine the clinical utility of these clusters.</p>","PeriodicalId":94376,"journal":{"name":"Microbiome research reports","volume":"5 1","pages":"4"},"PeriodicalIF":5.2,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}