{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:00:43Z","timestamp":1780639243331,"version":"3.54.1"},"reference-count":160,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Early life stress (ELS) is a major risk factor for disorders of gut-brain interaction (DGBIs), particularly irritable bowel syndrome (IBS), through the induction of persistent visceral hypersensitivity. This review synthesizes evidence from epidemiological studies, clinical observations, and preclinical models to establish ELS-induced visceral hypersensitivity as a core pathophysiological axis. I delineate the multi-level mechanisms underlying this phenomenon, encompassing: (1) central neuroendocrine dysregulation (hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor signaling) with epigenetic modifications (histone acetylation, non-coding RNAs) in limbic circuits; (2) spinal sensitization via brain-derived neurotrophic factor upregulation, glutamate transporter dysfunction, and potassium channel downregulation; (3) peripheral alterations including enterochromaffin cell hyperplasia, mast cell activation, enteric glial phenotypic switching, barrier disruption, and microbiota dysbiosis. I highlight critical modifiers including sexual dimorphism (estrogen-dependent mechanisms) and resilience factors (benevolent childhood experiences, environmental enrichment). Finally, I present a translational roadmap integrating pharmacological, nutritional, and behavioral interventions targeting ELS-programmed dysfunction along the brain-gut axis, emphasizing opportunities for prevention and precision medicine.<\/jats:p>","DOI":"10.3389\/fcell.2026.1827148","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:08:27Z","timestamp":1780636107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early life stress and the pathogenesis of visceral hypersensitivity: mechanisms and implications for disorders of gut-brain interaction"],"prefix":"10.3389","volume":"14","author":[{"given":"Enfu","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Neonatology and NICU, Wenling Maternal and Child Healthcare Hospital","place":["Wenling, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"509681","DOI":"10.3389\/fpsyt.2020.509681","article-title":"Animal Models for Functional Gastrointestinal Disorders","volume":"11","author":"Accarie","year":"2020","journal-title":"Front. 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