{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T15:10:49Z","timestamp":1778425849808,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2014from the acidic stomach to the anaerobic colon\u2014thereby 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.<\/jats:p>","DOI":"10.3390\/cells15010045","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:07:58Z","timestamp":1766714878000},"page":"45","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Muco-Microbiotic Interface as a Hub for Microbial Metabolites and Immune Regulation in Gastroenteric Health and Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1604-0285","authenticated-orcid":false,"given":"Adelaide","family":"Carista","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melania Ionelia","family":"Gratie","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7094-4336","authenticated-orcid":false,"given":"Enrico","family":"Tornatore","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Accomando","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialities \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-822X","authenticated-orcid":false,"given":"Giovanni","family":"Tomasello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0553-536X","authenticated-orcid":false,"given":"Domiziana","family":"Picone","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-5612","authenticated-orcid":false,"given":"Stefano","family":"Burgio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-1148","authenticated-orcid":false,"given":"Francesco","family":"Cappello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"G348","DOI":"10.1152\/ajpgi.00047.2013","article-title":"Studies of mucus in mouse stomach, small intestine, and colon. 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