{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:58Z","timestamp":1787026558561,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"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>Background &amp;amp; Aims<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa characterized by recurrent flares and difficulty achieving sustained remission. Renshen-Baidu-San (BDS), a classical Chinese herbal prescription, has shown promising clinical benefit in relieving UC symptoms, but its underlying therapeutic mechanisms remain insufficiently defined. This study aimed to elucidate the multiple biological mechanisms underlying the therapeutic effects of BDS in UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized an integrated multi-omics and experimental approach, combining serum metabolomics, pharmacological network analysis, molecular docking, and single-cell RNA sequencing in a DSS-induced UC mouse model, supplemented by colon organoid experiments. Key findings were validated using histopathology, immunohistochemistry, immunofluorescence, quantitative RT-PCR, ELISA, and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum metabolomics demonstrated that BDS modulates steroid- and lipid-derived metabolites, thereby influencing steroid hormone biosynthesis, bile acid turnover, and lipid pathways including arachidonic acid and linoleic acid metabolism. Network pharmacology based on serum-detected components further highlighted BDS\u2019s regulatory effects on inflammatory signaling and cellular proliferation, while molecular docking identified stable and favorable protein-ligand interactions. Single-cell transcriptomics revealed that BDS corrected UC-induced epithelial\u2013immune dysregulation, with Tuft and T-1 cell subclusters emerging as key responders through coordinated suppression of NF-\u03baB\u2013driven TNF-\u03b1 signaling; ligand\u2013receptor analysis indicated restoration of epithelial\u2013immune communication. Colon organoid experiments corroborated mucosal repair, crypt structural recovery, Tuft cell expansion, and a shift toward a tissue-restorative type 2 immune profile, characterized by elevated IL-4 and IL-25 and reduced IL-13.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that BDS treatment in DSS-induced colitis is accompanied by alterations in metabolic pathways, epithelial-immune communication, and cell-type-specific transcriptional programs, which may be relevant to type 2 immune\u2013mediated mucosal repair processes.<\/jats:p>\n                  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