Glyphosate Promotes the Spread of Antibiotic Resistance Genes in the Intestine: An Overlooked Environmental Risk

Glyphosate (Gly) is currently the most commonly used broad-spectrum herbicide in the world. The extensive residues of Gly and its major metabolite aminomethylphosphonic acid (AMPA) in food and the environment make it inevitable for humans to consume them. Although Gly has been shown to disturb the homeostasis of gut microbiome by inhibiting the shikimic acid pathway of microorganisms, the potential health effects [such as the occurrence of antibiotic resistance genes (ARGs)] remain unclear. Furthermore, as antibiotics that also act on the intestinal microbiota, their extensive residues inevitably lead to co-exposure with Gly. For these reasons, this study used zebrafish as experimental organisms to explore the effects of Gly/AMPA and oxytetracycline (OTC) exposure alone or in combination on ARGs in the intestine. Our results indicate that Gly exposure, rather than AMPA exposure, led to a 1.67-fold increase in the relative abundance of ARGs in the zebrafish intestine. Combined exposure to Gly and OTC led to a 2.30-fold increase in the relative abundance of ARGs in the zebrafish intestine, indicating a synergistic effect, whereas the additive effect of AMPA and OTC was negligible. In conclusion, the health risk of antibiotic resistance caused by Gly through the gut microbiota is a neglected hot topic. Further studies are needed to clarify Gly-induced functional drug resistance and to assess the human relevance of these findings using more appropriate model organisms.