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Here, we identify a significant reduction of Lactobacillus reuteri in both ALD patients and mouse models compared with their respective healthy controls. Using fecal microbiota transplantation, we first establish a causative role of the dysbiotic gut microbiota in driving ALD pathophysiology. In line with this finding, oral supplementation with L.\u00a0reuteri ameliorates ALD phenotypes. Mechanistically, L.\u00a0reuteri activates the farnesoid X receptor (FXR) signaling pathway, thereby restoring bile acid homeostasis, as evidenced by reduced levels of cholic acid (CA) and deoxycholic acid (DCA). The functional importance of FXR is further validated in Fxr\u2212\/\u2212 mice, where the protective effects of L.\u00a0reuteri on both ALD and bile acid metabolism are largely abrogated. Moreover, both in vitro and in vivo experiments confirm that CA and DCA directly compromise hepatocyte viability and exacerbate liver injury, reinforcing their roles as pathogenic effectors downstream of FXR dysregulation. Expanding upon these mechanistic insights, we identify the natural compound echinacoside as a gut microbiota-targeting intervention that not only enriches L.\u00a0reuteri but also potentiates FXR signaling, leading to significant improvement of ALD. Collectively, our findings define a microbiota-host metabolic axis centered on L.\u00a0reuteri and FXR-dependent bile acid homeostasis, offering a conceptual framework for targeting host\u2013microbe interactions in ALD.<\/jats:p>","DOI":"10.1093\/ismejo\/wrag153","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:13:58Z","timestamp":1781612038000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Lactobacillus reuteri<\/i>\n                    targets farnesoid X receptor-dependent bile acid homeostasis to ameliorate alcoholic liver disease"],"prefix":"10.1093","volume":"20","author":[{"given":"Shuo","family":"Yuan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University , No. 2, Anzhen Road, Chaoyang District, Beijing 100029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Beihua University , No. 12, Jiefang Middle Road, Chuanying District, Jilin City, Jilin Province 132011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Du","sequence":"additional","affiliation":[{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University , No. 2, Anzhen Road, Chaoyang District, Beijing 100029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlan","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Tu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , No. 38, Xueyuan Road, Haidian District, Beijing 100191 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