{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:30:42Z","timestamp":1786595442667,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Resveratrol is a dietary polyphenol found in grapes, peanuts, and berries, with reported anti-inflammatory, immunomodulatory, barrier-protective, and microbiota-regulating properties. Functional dyspepsia (FD) is associated with duodenal immune dysregulation, epithelial barrier impairment, and microbial imbalance, suggesting an active mucosal microenvironment. This study therefore examined whether resveratrol could alleviate FD-like pathological changes. We also examined its links with epithelial homeostasis, gut microbiota, and chemokine- or cytokine-related ligand\u2013receptor signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An FD-like mouse model was established and treated with resveratrol. Gastric emptying was assessed, and duodenal histopathology was examined by hematoxylin\u2013eosin staining, including epithelial injury, goblet cell alterations, crypt disorganization, and inflammatory cell infiltration. Toluidine blue staining assessed mast cell accumulation. RNA sequencing, GO\/KEGG enrichment, and protein\u2013protein interaction analyses characterized immune-related pathways, hub genes, and potential signaling networks. qPCR validated genes related to mucosal metabolism and epithelial function, chemokine- and cytokine-related ligand\u2013receptor signaling genes, mast cell markers, and epithelial barrier genes. 16S rRNA sequencing assessed gut microbial changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FD-like mice showed delayed gastric emptying, duodenal mucosal injury, inflammatory cell infiltration, goblet cell alterations, crypt disorganization, and mast cell accumulation, indicating low-grade mucosal immune activation and epithelial barrier disturbance. Resveratrol improved gastric emptying, alleviated duodenal injury, and reduced mast cell infiltration. Transcriptomic analysis showed broad changes in immune-related programs, particularly those associated with antigen presentation, adaptive immune responses, pro-inflammatory signaling, chemokine and cytokine activity, and mucosal immune regulation. PPI and qPCR analyses further supported the regulation of mucosal homeostasis, candidate\n                      <jats:italic>Ccl2\u2013Ccr2<\/jats:italic>\n                      ,\n                      <jats:italic>Il6\u2013Il6ra\/Il6st<\/jats:italic>\n                      , and\n                      <jats:italic>Tnf\u2013Tnfrsf1a<\/jats:italic>\n                      signaling, mast cell-associated immune activation, and epithelial barrier gene expression. Resveratrol also altered gut microbial \u03b2-diversity, community composition, ecological assembly, and predicted functions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Resveratrol attenuates FD-like gastric dysmotility and duodenal inflammatory injury, potentially by reducing mast cell-associated mucosal immune activation, modulating chemokine- and cytokine-related immune\u2013epithelial signaling, supporting epithelial barrier homeostasis, and reshaping gut microbiota.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906024","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:24:02Z","timestamp":1786595042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Resveratrol alleviates functional dyspepsia-like pathology by modulating chemokine- and cytokine-related immune\u2013epithelial signaling in the duodenal mucosa"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shenzhen Hospital, Southern Medical University","place":["Guangdong, China"]},{"name":"Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shenzhen Hospital, Southern Medical University","place":["Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Li","sequence":"additional","affiliation":[{"name":"Nutrition and Dietetic Services, Gloucestershire Royal Hospital, NHS Foundation Trust, National Health Service (NHS)","place":["Gloucester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeli","family":"Li","sequence":"additional","affiliation":[{"name":"Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan Traditional Chinese Medicine Hospital","place":["Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui Nicole","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Biosciences, Faculty of Life Sciences, University College London","place":["London, United Kingdom"]},{"name":"Department of Biological Chemistry, University of Michigan Ann Arbor","place":["Michigan, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fachao","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Cai","sequence":"additional","affiliation":[{"name":"Immunology Research Laboratory, Department of Research and Development, PyraGeo Biosciences Co., Ltd.","place":["Changsha, China"]},{"name":"Pharmacology Research Laboratory, Department of Research and Development, PyraGeo Biosciences Co., Ltd.","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30469-4","article-title":"Functional dyspepsia","volume":"396","author":"Ford","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.011","article-title":"Gastroduodenal 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