Highlights: What are the main findings? The gastrointestinal mucus is a dynamic ecosystem where mucins, mucus-associated microbiota, and extracellular vesicles form an integrated functional unit, defined here as the muco-microbiotic (MuMi) layer. The MuMi layer shows strong regional specialisation along the gastroenteric tract, shaping site-specific microbial niches, metabolite production, and immune interactions. What are the implications of the main findings? Viewing mucus, microbiota, and vesicular signalling as a single MuMi layer provides a unifying framework to better understand mucosal homeostasis and disease mechanisms, i.e., pathophysiology. This integrated perspective may improve experimental models and support the development of diagnostic and therapeutic strategies aimed at restoring mucosal barrier function in gastrointestinal disorders. The mucus layer covering the gastrointestinal tract forms a specialised interface where mucins, microbes, and extracellular vesicles create a dynamic, self-regulating ecosystem. Here, we introduce the concept of the muco-microbiotic layer as an integrated eco-physiological system that maintains mucosal homeostasis through coordinated structural, metabolic, and immune functions. The MuMi layer varies regionally in its biochemical composition, microbial inhabitants, and environmental parameters—from the acidic stomach to the anaerobic colon—thereby generating distinct niches for microbial colonisation and metabolite production. We summarise current evidence on how mucin glycans, mucus-associated microbiota, and vesicle-mediated signalling sustain barrier integrity, nutrient flux, and immune tolerance. Perturbations in any of these components lead to barrier failure, microbial encroachment, and inflammation, contributing to a broad spectrum of disorders, including gastritis, inflammatory bowel disease, colorectal cancer, and metabolic syndrome. Methodological advances such as organoid and mucus-on-chip models, spatial multi-omics, and vesiculomics are now enabling site-specific analyses of this complex system. Conceptually, defining the mucus, microbiota, and vesicular compartments as a single MuMi layer provides a new framework for understanding mucosal physiology and pathophysiology, emphasising the interdependence between structure and function. Integrating this perspective into experimental and clinical research may open new avenues for diagnostics and therapies targeting mucosal health.
Exploring the Muco-Microbiotic Interface as a Hub for Microbial Metabolites and Immune Regulation in Gastroenteric Health and Disease
Burgio, Stefano
;
2025-01-01
Abstract
Highlights: What are the main findings? The gastrointestinal mucus is a dynamic ecosystem where mucins, mucus-associated microbiota, and extracellular vesicles form an integrated functional unit, defined here as the muco-microbiotic (MuMi) layer. The MuMi layer shows strong regional specialisation along the gastroenteric tract, shaping site-specific microbial niches, metabolite production, and immune interactions. What are the implications of the main findings? Viewing mucus, microbiota, and vesicular signalling as a single MuMi layer provides a unifying framework to better understand mucosal homeostasis and disease mechanisms, i.e., pathophysiology. This integrated perspective may improve experimental models and support the development of diagnostic and therapeutic strategies aimed at restoring mucosal barrier function in gastrointestinal disorders. The mucus layer covering the gastrointestinal tract forms a specialised interface where mucins, microbes, and extracellular vesicles create a dynamic, self-regulating ecosystem. Here, we introduce the concept of the muco-microbiotic layer as an integrated eco-physiological system that maintains mucosal homeostasis through coordinated structural, metabolic, and immune functions. The MuMi layer varies regionally in its biochemical composition, microbial inhabitants, and environmental parameters—from the acidic stomach to the anaerobic colon—thereby generating distinct niches for microbial colonisation and metabolite production. We summarise current evidence on how mucin glycans, mucus-associated microbiota, and vesicle-mediated signalling sustain barrier integrity, nutrient flux, and immune tolerance. Perturbations in any of these components lead to barrier failure, microbial encroachment, and inflammation, contributing to a broad spectrum of disorders, including gastritis, inflammatory bowel disease, colorectal cancer, and metabolic syndrome. Methodological advances such as organoid and mucus-on-chip models, spatial multi-omics, and vesiculomics are now enabling site-specific analyses of this complex system. Conceptually, defining the mucus, microbiota, and vesicular compartments as a single MuMi layer provides a new framework for understanding mucosal physiology and pathophysiology, emphasising the interdependence between structure and function. Integrating this perspective into experimental and clinical research may open new avenues for diagnostics and therapies targeting mucosal health.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
