Fluazinam Caused Liver Metabolism Disorders and Intestinal Inflammation by Affecting Gut–Liver Axis in Mice

TY - JOUR

T1 - Fluazinam Caused Liver Metabolism Disorders and Intestinal Inflammation by Affecting Gut–Liver Axis in Mice

AU - He, Bingying

AU - Xiong, Yabing

AU - Sun, Mingjing

AU - Xiao, Shouchun

AU - Cao, Yue

AU - Yang, Jiaxing

AU - Shi, Xinlei

AU - Liu, Xueke

AU - Liu, Donghui

AU - Wang, Peng

N1 - Publisher Copyright: © 2026 American Chemical Society

PY - 2026/4/1

Y1 - 2026/4/1

N2 - Fluazinam is a widely used agricultural fungicide, but the effects of subchronic exposure remain unclear. This study investigated the liver and intestinal toxicity of fluazinam in mice exposed for 12 weeks at 0.01 and 1 mg/kg bw/day. Results showed that fluazinam caused weight loss, metabolic disorders, and liver toxicity. 16S rRNA sequencing revealed gut microbiota dysbiosis, which is associated with impaired intestinal barrier function and inflammation. Notably, the abundance of bile-acid-metabolizing bacteria (such as Lactobacillus, Lachnospiraceae, and Muribaculum) decreased. Mechanistically, this abnormality triggered a cascade reaction via the gut–liver axis, leading to decreased total bile acid levels, downregulated hepatic synthesis genes (Cyp7a1, Cyp8b1), and upregulated intestinal Fgf15. These changes impaired the farnesoid X receptor pathway and bile acid metabolism, exacerbating liver and intestinal damage. This study revealed that fluazinam mediated metabolic toxicity through the gut–liver axis, providing a novel perspective for its health risk assessment.

AB - Fluazinam is a widely used agricultural fungicide, but the effects of subchronic exposure remain unclear. This study investigated the liver and intestinal toxicity of fluazinam in mice exposed for 12 weeks at 0.01 and 1 mg/kg bw/day. Results showed that fluazinam caused weight loss, metabolic disorders, and liver toxicity. 16S rRNA sequencing revealed gut microbiota dysbiosis, which is associated with impaired intestinal barrier function and inflammation. Notably, the abundance of bile-acid-metabolizing bacteria (such as Lactobacillus, Lachnospiraceae, and Muribaculum) decreased. Mechanistically, this abnormality triggered a cascade reaction via the gut–liver axis, leading to decreased total bile acid levels, downregulated hepatic synthesis genes (Cyp7a1, Cyp8b1), and upregulated intestinal Fgf15. These changes impaired the farnesoid X receptor pathway and bile acid metabolism, exacerbating liver and intestinal damage. This study revealed that fluazinam mediated metabolic toxicity through the gut–liver axis, providing a novel perspective for its health risk assessment.

KW - bile acid

KW - fluazinam

KW - gut−liver axis

KW - intestinal homeostasis

KW - liver injury

UR - https://www.scopus.com/pages/publications/105034857832

U2 - 10.1021/acs.jafc.5c14080

DO - 10.1021/acs.jafc.5c14080

M3 - Article

C2 - 41848155

SN - 0021-8561

VL - 74

SP - 10063

EP - 10074

JO - Journal of agricultural and food chemistry

JF - Journal of agricultural and food chemistry

IS - 12

ER -