{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:36:48Z","timestamp":1790285808442,"version":"4.1.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"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. Nutr."],"abstract":"<jats:p>\n                    Bile acids (BAs), once regarded primarily as detergents facilitating lipid digestion, are now recognized as pivotal signaling molecules that orchestrate intestinal and systemic physiology through a diverse network of nuclear and membrane receptors, with distinct receptor classes mediating complementary transcriptional and rapid signaling responses, including Farnesoid X Receptor (FXR), Takeda G protein-coupled Receptor 5 (TGR5), Pregnane X Receptor (PXR), Peroxisome Proliferator-Activated Receptor\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (PPAR\u03b1), Vitamin D Receptor (VDR), and Mas-related G protein-coupled Receptor member X4 (MRGPRX4). This review synthesizes recent advances in understanding the molecular architecture of BA signaling, emphasizing receptor structural diversity, spatiotemporal expression patterns along the gastrointestinal tract, ligand specificity shaped by BA chemical modifications, and the emerging roles of microbiota-derived bile acid derivatives and selected non-canonical host targets in intestinal immune and metabolic regulation. Central to this signaling axis is the gut microbiome, which enzymatically reprograms the BAs pool through deconjugation, dehydroxylation, oxidation, and epimerization, as well as emerging reconjugation\/amidation pathways, thereby generating classical secondary BAs as well as structurally novel metabolites that modulate host receptor activity and immune-cell programs. In turn, BAs shape microbial composition, establishing a dynamic bidirectional feedback loop critical for maintaining intestinal homeostasis. In addition to classical receptor signaling, selected microbiota-derived BAs metabolites can also influence immune-associated transcriptional regulators, thereby expanding the scope of BAs signaling in mucosal immune homeostasis. Beyond metabolism, BAs-receptor interactions integratively regulate gut barrier integrity via tight junction reinforcement, modulate immune responses through anti-inflammatory pathways and tolerogenic cell induction, and influence gut motility and neuroendocrine signaling. Dysregulation of BAs receptor and metabolite-mediated signaling axes is increasingly implicated in the pathogenesis of inflammatory bowel disease, bile acid malabsorption, diarrhea-predominant irritable bowel syndrome, colorectal cancer\u2014via DNA damage and Wnt\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -catenin pathway activation\u2014and systemic conditions such as obesity, non-alcoholic fatty liver disease, and sepsis-related intestinal injury. Emerging therapeutic strategies aim to restore BAs signaling balance through next-generation receptor modulators, tissue-targeted delivery systems, microbiome-directed interventions, rational use of sequestrants, and synergistic combination therapies, thereby supporting the development of more precise and mechanism-based interventions. Future progress will hinge on interdisciplinary approaches integrating metabolomics, gnotobiotic models, and clinical translation to harness the full therapeutic potential of the BAs signaling network in gastrointestinal and metabolic health.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2026.1821418","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:33:54Z","timestamp":1776749634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Advances in research on the effects of bile acids and their receptors on intestinal function"],"prefix":"10.3389","volume":"13","author":[{"given":"Yulin","family":"Cheng","sequence":"first","affiliation":[{"name":"Sichuan Cancer Hospital and Institute","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sichuan Cancer Hospital and Institute","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuhou District People\u2019s Hospital","place":["Chengdu, China"]},{"name":"Wuhou District Health Hospital Woman and Children","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiu","family":"Yu","sequence":"additional","affiliation":[{"name":"Sichuan Cancer Hospital and Institute","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"G201","DOI":"10.1152\/ajpgi.00125.2021","article-title":"Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels","volume":"322","author":"Keely","year":"2021","journal-title":"Am J Physiol Gastrointest Liver 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