2026-10-09T22:16:53Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34027666 2026-09-29T21:04:03Z category_4 category_7 category_8 category_12 category_13 category_14 category_16 category_21 category_873 category_39 category_46 category_64 category_69 portal_63 item_type_6 month_year_09_2026

6:2 Chlorinated Polyfluoroalkyl Ether Sulfonate Exposure Disrupts the Gut-Liver Axis and Induces Inflammatory-Dominant Hepatotoxicity via Bile Acid-Farnesoid X Receptor Signaling Jinni Zhang (17241533) Jing Tang (33607) Wen Xie (104834) Yajing Zhang (1760800) Yu He (420536) Zian Lin (1557547) Zongwei Cai (631593) Biochemistry Medicine Microbiology Cell Biology Genetics Molecular Biology Physiology Biotechnology Chemical Sciences not elsewhere classified Ecology Immunology Cancer Inorganic Chemistry toxicological evaluation revealed mechanistic analysis indicated kg body weight key mechanism contributing findings verify disruption estimated daily doses bile acid homeostasis enhancing lipopolysaccharide translocation induced liver injury bile acid axis gut microbiota dysbiosis obeticholic acid elevated lipopolysaccharide liver axis widely used pharmacological activation pfos ), oxidative stress mechanisms underlying liver dysfunction knowledge gap induces inflammatory frequently detected environmental media electroplating industry approximately 0 alleviated hepatotoxicity 78 μg 26 weeks 2 cl 6:2 Chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), as an alternative of perfluorooctanesulfonate (PFOS), has been widely used in the electroplating industry and frequently detected in environmental media. 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 μg/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. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acs.est.6c09647.s001 https://figshare.com/articles/journal_contribution/6_2_Chlorinated_Polyfluoroalkyl_Ether_Sulfonate_Exposure_Disrupts_the_Gut-Liver_Axis_and_Induces_Inflammatory-Dominant_Hepatotoxicity_via_Bile_Acid-Farnesoid_X_Receptor_Signaling/34027666 CC BY-NC 4.0