Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impacting gut and gut microbiota

BACKGROUND: Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 and CD-1 (ICR) mice fed high- or normal-fat diets. To further investigate the effects of chlorpyrifos-altered microbiota, antibiotic treatment and microbiota transplantation experiments were conducted. RESULTS: The results showed that chlorpyrifos caused broken integrity of the gut barrier, leading to increased lipopolysaccharide entry into the body and finally low-grade inflammation, while genetic background and diet pattern have limited influence on the chlorpyrifos-induced results. Moreover, the mice given chlorpyrifos-altered microbiota had gained more fat and lower insulin sensitivity. CONCLUSIONS: Our results suggest that widespread use of pesticides may contribute to the worldwide epidemic of inflammation-related diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-019-0635-4) contains supplementary material, which is available to authorized users.