Roundup-Induced\nGut Dysbiosis, Irrelevant to Aromatic\nAmino Acid Deficiency, Impairs the Gut Function in Rats

Glyphosate, the most popular herbicide globally, has\nlong been\nconsidered safe for mammals. However, whether glyphosate can disturb\ngut microbiota via inhibiting aromatic amino acid (AAA) synthesis\nhas been under debate recently. Here, we evaluated the impacts of\nchronic exposure to Roundup on gut health with the addition of AAA\nand explored the mechanism behind Roundup-induced gut dysfunction\nby performing fecal microbiota transplantation. 500 mg/kg·bw\nof Roundup, independent of AAA deficiency, caused severe damage to\ngut function, as characterized by gut microbial dysbiosis, oxidative\nstress damage, intestinal inflammation, and histopathological injury,\nparticularly in female rats. Notably, similar to Roundup, Roundup-shaped\ngut microbiome evidently damaged serum, cecum, and colon profiling\nof oxidative stress biomarkers (malonaldehyde (MDA), glutathione peroxidase\n(GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and H<sub>2</sub>O<sub>2</sub>). Moreover, it induced 0.65-, 3.29-, and 2.36-fold\nincreases in colonic IL-1β, IL-6, and TNF-α levels, and\n0.34-fold decreases in the IL-10 level. Upon transplanting healthy\nfecal microbiota to Roundup-treated rats, they exhibited a healthier\ngut microenvironment with mitigated inflammation, oxidative damage,\nand intestinal injury. Overall, our findings provide new insights\ninto the safety of Roundup, highlight the crucial role of gut microbiota\nin Roundup-induced gut dysfunction, and pave the way for developing\ngut-microbiota-based strategies to address Roundup-related safety\nissues.