{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:03:33Z","timestamp":1790154213341,"version":"4.0.1"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) develops through interactions among genetic susceptibility, intestinal microbiota, environmental exposures, and dysregulated mucosal immunity. Increasing evidence suggests that these interactions may begin before diagnosis\u2014and possibly before birth\u2014when maternal signals, microbial assembly, epithelial maturation, and immune education intersect. This narrative review synthesizes findings from human observational and cohort studies, experimental animal and cellular models, and mechanistic literature to examine how prenatal and early-life exposures may influence later IBD susceptibility. Human cohort studies associate later IBD with several early-life exposures, particularly repeated antibiotic use, whereas evidence for dietary, delivery, and household factors remains heterogeneous and vulnerable to confounding. Studies of pregnancies affected by IBD identify altered maternal and infant microbial and immune features but do not establish causality. Experimental models provide stronger mechanistic evidence that maternal microbial signals influence offspring immune development, neonatal epithelial cells acquire context-dependent tolerance, and microbial metabolites regulate regulatory T cells, type 17 immunity, barrier function, and chromatin-modifying enzymes. Histamine-receptor signaling further illustrates receptor-specific modulation of bacterial TLR (Toll-like receptors) responses in established IBD, although its role in early-life programming remains unproven. We propose a testable \u201cdevelopmental inflammatory set-point\u201d model in which cell type, tissue compartment, timing, signal intensity, and host genotype determine whether microbial sensing promotes tolerance or persistent inflammatory readiness. This model is biologically plausible but remains unvalidated as a predictor of human IBD.<\/jats:p>","DOI":"10.3390\/ijms27198458","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:14:39Z","timestamp":1790151279000},"page":"8458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal\u2013Fetal Exposome and Early-Life Microbiota\u2013Pattern Recognition Receptors Signaling in Inflammatory Bowel Disease Susceptibility: A Mechanistic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-9020","authenticated-orcid":false,"given":"Krzysztof","family":"Jurkiewicz","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Faculty of Medicine, Wroclaw Medical University, Parkowa 34, 51-616 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-2696","authenticated-orcid":false,"given":"Sylwia","family":"Smolinska-Wilczynska","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Faculty of Medicine, Wroclaw Medical University, Parkowa 34, 51-616 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.gastro.2023.03.238","article-title":"Defining interactions between the genome, epigenome, and the environment in inflammatory bowel disease: Progress and prospects","volume":"165","author":"Noble","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41577-019-0268-7","article-title":"Host\u2013microbiota interactions in inflammatory bowel disease","volume":"20","author":"Caruso","year":"2020","journal-title":"Nat. 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