2. Academic Validation
  3. Perfluorooctane sulfonates drives colitis via a gut microbiota-bile acid-endoplasmic reticulum stress axis in mice: Mechanistic validation and targeted interventions

Perfluorooctane sulfonates drives colitis via a gut microbiota-bile acid-endoplasmic reticulum stress axis in mice: Mechanistic validation and targeted interventions

  • J Hazard Mater. 2026 Feb 1:503:141122. doi: 10.1016/j.jhazmat.2026.141122.
Huanjuan Yan 1,  Changxiong Wang 2,  Haoran Wang 3,  Jian Liu 4,  Hongfei Zhou 5,  Wenxuan Zhong 5,  Xiaodong Wang 5,  Yongping Chen 5,  Zhiran Ju 6,  Haibin Tong 7,  Ya Zhang 8
Affiliations

Affiliations

  • 1 Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
  • 2 Department of Gastroenterology, Lishui Hospital of Traditional Chinese Medicine, Lishui 323000, China.
  • 3 Management Science, Lancaster University, Lancaster LA2 0PF, United Kingdom.
  • 4 Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China.
  • 5 Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 6 Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, State Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang University of Technology, Hangzhou 310000, China.
  • 7 Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China. Electronic address: [email protected].
  • 8 Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
PMID: 41538937 DOI: 10.1016/j.jhazmat.2026.141122
Abstract

Perfluorooctane sulfonate (PFOS), a widespread environmental pollutant, is implicated in systemic toxicity, yet its role in colitis remains unclear. This study aimed to investigate whether PFOS exacerbates colitis via the gut microbiota-bile acid-endoplasmic reticulum stress (ERS) axis and to explore potential interventions. Following 15-week oral PFOS exposure (0.1 or 0.3 mg/kg/d), mice developed dose-dependent colitis, featuring weight loss, colon shortening, barrier dysfunction, and elevated inflammation. High-dose PFOS disturbed bile acid homeostasis, depleting conjugated species like tauroursodeoxycholic acid (TUDCA) while accumulating deconjugated bile acids such as deoxycholic acid (DCA), thereby activating ERS pathways (PERK/eIF2α, IRE1/XBP1, ATF6). Gut microbiota analysis revealed reduced diversity, a lower Firmicutes/Bacteroidetes ratio, increased bacteria with bile salt hydrolase (BSH) activity (e.g., Lachnospira), and decreased potential bacteria (e.g., Akkermansia). Interventions with TUDCA, a BSH inhibitor, or fecal microbiota transplantation from healthy donors alleviated colitis, restored conjugated bile acids, and suppressed ERS. These findings demonstrate that PFOS triggers colitis via BSH-mediated bile acid deconjugation and ERS activation, highlighting the therapeutic potential of targeting this axis.

Keywords

Colitis; Endoplasmic reticulum stress; Gut microbiota; Perfluorooctane sulfonates; Tauroursodeoxycholic acid.

Figures
Products