{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:20:38Z","timestamp":1787721638651,"version":"build-2784847793"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric intestinal metaplasia (GIM) is a typical precancerous lesion of gastric cancer (PLGC). Previous studies have demonstrated that Xinkai Kujiang formula can effectively alleviate GIM, but its underlying mechanism remains largely unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The GIM rat model was established using 2% sodium salicylate and 20\u00a0mmol\/L sodium deoxycholate, and then the rats were treated with Banxia Xiexin Decoction (BXD) and Xinkai Kujiang Decoction (XKD) for 4 weeks. Multi-omics analyses including 16\u00a0S ribosomal RNA gene sequencing, transcriptomics, single-cell RNA sequencing, network pharmacology, and component identification were performed to explore the therapeutic mechanisms of Xinkai Kujiang formula on GIM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the model rats, severe gastric mucosal atrophy was observed, characterized by disordered glands and goblet cells. Following intervention with BXD and XKD, gastric mucosal thickness was restored, glandular structures became regularly arranged, and the number of metaplastic goblet cells markedly decreased. Microbiota profiling of gastric mucosa revealed significant enrichment of\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      and\n                      <jats:italic>Enterococcus<\/jats:italic>\n                      in the model group. These abundances were reduced in the BXD group, and short-chain fatty acid-producing bacteria such as\n                      <jats:italic>Alistipes<\/jats:italic>\n                      and\n                      <jats:italic>Lachnospira<\/jats:italic>\n                      were enriched. In the intestine, opportunistic pathogens like\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      and\n                      <jats:italic>Enterococcus<\/jats:italic>\n                      were enriched in the model group, whereas\n                      <jats:italic>Corynebacterium<\/jats:italic>\n                      and\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      were enriched in the XKD group. Transcriptomic analysis presented that BXD upregulated innate immune-related genes in the gastric mucosa, and single-cell RNA sequencing (scRNA-Seq) showed that XKD alleviated GIM by inhibiting the VEGF and HIF-1\u03b1 pathways, reducing angiogenesis, suppressing inflammatory infiltration, and regulating energy metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BXD and XKD improve gastrointestinal microbiota disorders and metabolic disorders, enhance gastric mucosal immunity, and inhibit the VEGF and HIF-1\u03b1 pathway. Collectively, these multi-omics data provide novel insights into the therapeutic mechanisms of Xinkai Kujiang formula for GIM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1881703","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:45:42Z","timestamp":1787719542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics integrated analysis to explore the molecular mechanisms of Xinkai Kujiang formula in treating gastric intestinal metaplasia in rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiao","family":"Xiang","sequence":"first","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoling","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]},{"name":"Laboratory Animal Center, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufen","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolai","family":"Hua","sequence":"additional","affiliation":[{"name":"Institute of Tumour Prevention and Control, Yangzhong People\u2019s Hospital","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Yangzhong People\u2019s Hospital","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1158\/0008-5472.CAN-15-2272","article-title":"Cdx2 expression and intestinal metaplasia induced by H. pylori infection of gastric cells is regulated by NOD1-mediated innate immune responses","volume":"76","author":"Asano","year":"2016","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1136\/gutjnl-2019-318930","article-title":"Single-cell transcriptional analyses of spasmolytic polypeptide-expressing metaplasia arising from acute drug injury and chronic inflammation in the stomach","volume":"69","author":"Bockerstett","year":"2020","journal-title":"Gut"},{"key":"B3","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat. 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