Dietary Glyphosate at the Regulatory "Safe" Level Worsens Colitis via a Gut Microbiota-Derived Palmitic Acid-JAK-STAT Pathway.

Glyphosate (GLY) has become a frequent pollutant in foodstuffs. While the link between GLY exposure and the high prevalence of inflammatory bowel disease (IBD) has been reported, the effects and mechanisms are largely unclear. Here, the impacts of GLY at the regulatory "safe" level on IBD progression were investigated in a mouse colitis model. Compared with the DSS group, the GLY + DSS group suffered from severe gut epithelial barrier injury and inflammatory response, accompanied by gut microbiota dysbiosis marked by increased abundance of Bacteroides thetaiotaomicron (B. thetaiotaomicron). The increase of B. thetaiotaomicron, which can produce palmitic acid (PA), resulted in PA accumulation and therefore upregulated the JAK-STAT pathway, exacerbating DSS-induced colitis. Supplementation with PA and viable B. thetaiotaomicron also exacerbated the experimental colitis. These findings highlight the significant role of GLY in the progression of IBD, even at the dose considered "safe" by regulatory standards. This research provides an experimental reference for GLY safety threshold re-evaluation.