Involvement of gut microbiota in chlorpyrifos-induced subchronic toxicity in mice

Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides all over the world. Unfortunately, long-term exposure to CPF may cause considerable toxicity to organisms. Some evidence suggests that the intestinal microbial community may be involved in regulating the toxicity of CPF. In this study, we explored if the intestinal microbial community is involved in regulating the toxicity of CPF. Adult mice were continuously exposed to CPF (4 mg/kg body weight /day) for 10 weeks with or without a 2-week pretreatment of antibiotics to change the ecological structure of intestinal microorganisms in advance. Pathological changes in the liver and kidneys were examined and the biochemical parameters in serum for liver and kidney functions were detected, and changes in the intestinal microbial community of the mice were measured. The results showed that subchronic exposure to low-dose CPF caused an ecological imbalance in the intestinal flora and caused pathological damage to the liver and kidneys. Serum biochemical indicators for liver function such as alanine aminotransferase and total bile acids contents and renal biochemical indicators such as urea nitrogen and creatinine were disrupted. Changes in intestinal microbial community structure by using antibiotics in advance can effectively alleviate the pathological and functional damage to the liver and kidneys caused by CPF exposure. Further analysis showed that intestinal microorganisms such as Saccharibacteria (TM7), Odoribacter, Enterococcus and AF12 genera may be involved in managing the toxicity of CPF. Together, our results indicated that long-term low-dose CPF exposure could induce hepatotoxicity and nephrotoxicity, and liver and kidney damage may be mitigated by altering the ecology of intestinal microorganisms.