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However, the mechanisms underlying its chronic hepatotoxicity remain incompletely understood, particularly with respect to the gut-liver axis and bile acid homeostasis. To address this knowledge gap, mice were exposed to 6:2 Cl-PFESA via drinking water for 26 weeks, resulting in estimated daily doses of approximately 0.72 and 7.78 \u03bcg\/kg body weight. Toxicological evaluation revealed that prolonged 6:2 Cl-PFESA exposure induced hepatic steatosis, oxidative stress, inflammation, and liver dysfunction, accompanied by gut microbiota dysbiosis, colonic inflammation, and elevated lipopolysaccharide (LPS) levels in the colon and liver. Mechanistic analysis indicated that long-term 6:2 Cl-PFESA exposure suppressed hepatic farnesoid X receptor (FXR) signaling, thereby disrupting bile acid homeostasis, inducing gut microbiota dysbiosis, and enhancing lipopolysaccharide translocation, ultimately aggravating liver injury. Notably, pharmacological activation of FXR by obeticholic acid (OCA) partially restored bile acid homeostasis and alleviated hepatotoxicity. Collectively, these findings verify disruption of the gut-liver FXR-bile acid axis as a key mechanism contributing to 6:2 Cl-PFESA-induced liver injury.<\/jats:p>","DOI":"10.1021\/acs.est.6c09647","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:02:03Z","timestamp":1790719323000},"page":"28524-28538","source":"Crossref","is-referenced-by-count":0,"title":["6:2\nChlorinated Polyfluoroalkyl Ether Sulfonate Exposure\nDisrupts the Gut-Liver Axis and Induces Inflammatory-Dominant Hepatotoxicity\nvia Bile Acid-Farnesoid X Receptor Signaling"],"prefix":"10.1021","volume":"60","author":[{"given":"Jinni","family":"Zhang","sequence":"first","affiliation":[{"name":"Fuzhou University , , ,","place":["Fuzhou, China, 350108"]},{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"Fuzhou University , , ,","place":["Fuzhou, China, 350108"]},{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-1376","authenticated-orcid":true,"given":"Wen","family":"Xie","sequence":"additional","affiliation":[{"name":"Fuzhou University , , ,","place":["Fuzhou, China, 350108"]},{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fuzhou University , , ,","place":["Fuzhou, China, 350108"]},{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4487-1047","authenticated-orcid":true,"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0866-0711","authenticated-orcid":true,"given":"Zian","family":"Lin","sequence":"additional","affiliation":[{"name":"Fuzhou University , , ,","place":["Fuzhou, China, 350108"]},{"name":"Fuzhou University , , , ,","place":["Fuzhou, Fujian, China, 350108"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Eastern Institute of Technology , , ,","place":["Ningbo, Zhejiang, China, 315100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"issue":"5","key":"2026101310152082200_cit1","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1021\/acs.est.6b04806","article-title":"A never-ending story\nof per- and polyfluoroalkyl substances (PFASs)?","volume":"51","author":"Wang","year":"2017","journal-title":"Environ. 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