Hepatic toxicity induced by exposure to glyphosate/aminomethylphosphonic acid and oxytetracycline alone or in combination in zebrafish: A novel mechanism of the gut-liver axis

Glyphosate (Gly) is the most commonly used herbicide in the world. Glyphosate and its main degradation product, aminomethylphosphonic acid (AMPA), are often detected in aquatic environments and may pose a threat to the health of aquatic organisms. It is well established that Gly is mainly enriched in the intestine and degraded into AMPA. However, it remains unclear whether they disrupt the gut microbiota and cause liver health effects, as well as whether they have a synergistic effect with antibiotics. We investigated herein the effects of zebrafish exposure to Gly, AMPA and oxytetracycline (OTC) alone or in combination on the gut-liver axis. Our results suggest that Gly, AMPA, and OTC induce lipid accumulation, inflammatory response and oxidative damage in the liver, which is associated with a higher Firmicutes/Bacteroidetes ratio in the intestine and a higher levels of lipopolysaccharide in serum. Compared with the single exposure groups (OTC, Gly, and AMPA), the toxic effects of the gut-liver axis were more severe in the combined exposure groups (Gly+OTC, AMPA+OTC). Our results indicate that the health risks posed by Gly, AMPA and OTC through the gut microbiota of aquatic organisms are a neglected hot spots.