Microbiota–mucosal crosstalk in colitis: from molecular signaling to precision immunometabolism

The field of microbiota–mucosal biology examines how gut microorganisms, epithelial barriers, and immune networks interact to regulate intestinal homeostasis and inflammation. In colitis and inflammatory bowel disease (IBD), disruption of this interface is associated with impaired barrier function, altered microbial communities, dysregulated innate and adaptive immunity, and persistent tissue inflammation. Key questions remain concerning how specific microbial signals initiate or resolve colitis, why individuals with similar clinical phenotypes exhibit different microbial and immune profiles, and which host–microbiota interactions are causally linked to therapeutic outcomes. Recent studies indicate that short-chain fatty acids, tryptophan-derived metabolites, bile acid intermediates, and other microbial products influence T helper 17/regulatory T-cell balance, macrophage polarization, epithelial integrity, and immunometabolic pathways involving AhR, HIF, NLRP3, and mTOR. Multi-omics, organoid, gnotobiotic, and spatial approaches are increasingly clarifying these mechanisms, while microbiota-targeted interventions show promise in experimental and clinical settings. However, causal validation, inter-individual heterogeneity, context-dependent microbial effects, and limited clinical translatability continue to constrain progress. A more integrated investigation of molecular signaling, cellular metabolism, microbial ecology, and treatment response is therefore needed.This Research Topic aims to define the mechanisms governing microbiota–mucosal crosstalk during the initiation, progression, and resolution of colitis, with particular emphasis on immunometabolic regulation and therapeutic translation. It will explore how microbial communities and their metabolites shape epithelial and immune functions, identify molecular and cellular nodes that may be therapeutically targeted, and assess how microbiome-informed strategies can improve precision prevention and treatment in IBD. Contributions may address causal mechanisms, biomarkers of disease or treatment response, and hypotheses linking microbial composition or function with distinct immunological and clinical phenotypes.To gather further insights into host–microbiota interactions in colitis and their relevance to precision IBD therapy, this Research Topic will focus on mechanistic, translational, and computational studies while acknowledging the limitations of model systems, cohort variability, and clinical generalisability. We welcome articles addressing, but not limited to, the following themes:• Structural and functional interactions among the gut microbiota, epithelial barrier, goblet cells, and mucosal immune cells.• Microbiota-driven regulation of innate and adaptive immune networks, including T-cell differentiation and macrophage polarization.• Roles of short-chain fatty acids, tryptophan derivatives, bile acids, and other microbial metabolites in intestinal inflammation.• AhR–HIF–NLRP3–mTOR and related metabolic signaling axes in colitis.• Nutritional modulation, probiotics, synbiotics, postbiotics, and other microbiota-targeted interventions.• Engineered delivery systems and microbiome-informed therapeutic platforms.• Multi-omics, spatial profiling, organoid, gnotobiotic, and computational approaches for resolving microbiota–immune interactions.• Artificial intelligence for biomarker discovery and prediction of therapeutic responsiveness.• Mechanistic validation, inter-individual heterogeneity, and strategies for improving clinical translation.The Research Topic welcomes original research articles and high-impact review articles. Topic editors: Hongcai Li, Mengzhen Han, Jingjing Liang Source: https://www.frontiersin.org/research-topics/84003/microbiota-mucosal-crosstalk-in-colitis-from-molecular-signaling-to-precision-immunometabolism