{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:06:06Z","timestamp":1788458766979,"version":"build-2803163510"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"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. Infect. Microbiol."],"abstract":"<jats:p>The bidirectional communication between the gut microbiota (GM) and the enteric nervous system (ENS) is fundamental for gastrointestinal homeostasis. This review dissects the intricate GM\u2013ENS dialogue, emphasizing its transition from a developmental programmer in early life to a sustained regulator of neural plasticity in adulthood. We synthesize the core signaling mechanisms\u2014microbial metabolites, neuroactive substances, and immune mediators\u2014that orchestrate ENS activity. We further propose a multi\u2212timescale model (rapid neuropod\/bioelectric, intermediate metabolite, slow immune) with differential relevance to irritable bowel syndrome (IBS) (fast distortions) versus inflammatory bowel disease(IBD)(slow amplification). Critically, we delineate how this axis adopts distinct pathophysiological roles across major digestive disorders: acting as a \u201csignal distorter\u201d in IBS, an \u201cinflammation amplifier\u201d in IBD, and a \u201ctumor accomplice\u201d in colorectal cancer (CRC). By integrating these mechanistic insights with emerging therapeutic paradigms (e.g., precision biomarkers, synthetic microbial consortia, postbiotics), we position the GM\u2013ENS axis as a central hub for understanding disease pathogenesis and a promising framework for developing next-generation precision medicine strategies.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1852596","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:40:00Z","timestamp":1781070000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The gut microbiota-enteric nervous system axis: from bidirectional programming to precision therapeutics in digestive diseases"],"prefix":"10.3389","volume":"16","author":[{"given":"Huimin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, China"]},{"name":"Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, China"]},{"name":"Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, China"]},{"name":"Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, China"]},{"name":"Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, China"]},{"name":"Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1007\/s10620-017-4662-3","article-title":"Attenuated GABAergic signaling in intestinal epithelium contributes to pathogenesis of ulcerative colitis","volume":"62","author":"Aggarwal","year":"2017","journal-title":"Dig. 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