Chronic Exposure to Fluxapyroxad Exacerbated Susceptibility to Colitis in Mice via a Gut Microbiota–Indole Derivatives–Th17/Treg Cell Balance Axis DOI
Yue Cao,

Shouchun Xiao,

Bingying He

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored underlying mechanisms based a mouse model. After 13 weeks of exposure at acceptable daily intake (ADI) level, fluxapyroxad exacerbated to colitis, impaired intestinal barrier, elevated proinflammatory cytokines chemokines colon in mice. It was found that this toxic effect caused by disruption gut microbiome. Specifically, abundance Lachnospiraceae Muribaculaceae decreased, while Desulfovibrionaceae Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic (IAA), indole-3-acrylic (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis overactivating Th17 cells insufficient Treg cell differentiation, causing mild colonic inflammation. Oral antibiotic-treated mice transfer experiments validated pathway. Susceptibility induced not detected oral Fecal disordered could aggravate severity recipient did receive exposure. In conclusion, chronic ADI level via microbiota-indole derivatives-Treg/Th17 balance axis, offering new risk assessment perspective fluxapyroxad.

Language: Английский

Chronic Exposure to Fluxapyroxad Exacerbated Susceptibility to Colitis in Mice via a Gut Microbiota–Indole Derivatives–Th17/Treg Cell Balance Axis DOI
Yue Cao,

Shouchun Xiao,

Bingying He

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored underlying mechanisms based a mouse model. After 13 weeks of exposure at acceptable daily intake (ADI) level, fluxapyroxad exacerbated to colitis, impaired intestinal barrier, elevated proinflammatory cytokines chemokines colon in mice. It was found that this toxic effect caused by disruption gut microbiome. Specifically, abundance Lachnospiraceae Muribaculaceae decreased, while Desulfovibrionaceae Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic (IAA), indole-3-acrylic (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis overactivating Th17 cells insufficient Treg cell differentiation, causing mild colonic inflammation. Oral antibiotic-treated mice transfer experiments validated pathway. Susceptibility induced not detected oral Fecal disordered could aggravate severity recipient did receive exposure. In conclusion, chronic ADI level via microbiota-indole derivatives-Treg/Th17 balance axis, offering new risk assessment perspective fluxapyroxad.

Language: Английский

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