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Bile acids (BAs), a class of steroid compounds regulated by the host and microbes, are increasingly shown to become dysregulated in models of depression. However, the identity of key regulatory BA metabolite in patients with MDD and associated mechanism remain to be clarified. Here, a prospective observational study in patients with depression (\n                    <jats:italic>n<\/jats:italic>\n                    = 235) and control subjects (\n                    <jats:italic>n<\/jats:italic>\n                    = 232) for identifying functional BA metabolites regulating depressive behavior and brain functional connectivity is performed. Using comparative metabolomics assay, an increased level of taurocholic acid (TCA) in the serum of patients with MDD is observed, which is reversed by anti\u2010depressant treatments. Transferring fecal microbiome from patients with MDD induced TCA accumulation to the hippocampus of recipient mice exhibiting depression\u2010like behavior. TCA supplementation suppressed hippocampal neurogenesis, triggered microglial activation, and elicited depression\u2010like behavior in mice, which are alleviated by a sphingosine\u20101\u2010phosphate receptor 2 (S1PR2) antagonist. In patients with MDD, functional neuroimaging and spearman correlation analysis revealed that circulating TCA is strongly correlated with functional connectivity in the subregions of hippocampus. The results highlight the potential of harnessing TCA as a prognostic marker and therapeutic target for depression.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508693","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T04:13:54Z","timestamp":1766549634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Taurocholic Acid Is Associated With Disturbed Functional Connectivity in the Hippocampus of Patients With Depression"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3490-5603","authenticated-orcid":false,"given":"Xiaoying","family":"Cai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taipeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"},{"name":"Department of Medical Psychology Huai'an Third People's Hospital  Huaian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhen","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchi","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychosomatics Zhongda Hospital School of Medicine Jiangsu Provincial Key Laboratory of Brain Science and Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 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