Dietary exposure to a pesticide mixture aggravates inflammation and microbiota dysbiosis in a murine model of food allergy and asthma

The prevalence of allergic diseases is increasing worldwide, and their precise causes are not fully understood. However, this observation can be correlated with increasing chemical pollution of the environment. Pesticide exposure alters immune system, microbiota and barrier functions. Here, we studied the effect of dietary exposure to a pesticide mixture at levels under the tolerable daily intake (TDI) to understand the combined effect of pesticide exposure on food allergy (FA) and allergic asthma (AA) development. Using mouse models of FA and AA, we evaluated the effects of direct exposure via diet during pregnancy and childhood to a mixture of six common pesticides used on fruits at treatment doses under the TDI. We studied allergic symptoms, gut physiology, immune responses and the microbiota. Specific IgE and Th2 immune responses were increased in allergic mice exposed to the pesticide cocktail. Similarly, the increase in transcellular permeability induced by food allergies was markedly aggravated by exposure to pesticides. Moreover, exposure to a pesticide cocktail induced gut dysbiosis and decreased the microbial diversity induced by food allergies. Dysbiosis is characterized by bacterial changes, including a decrease in bacterial diversity and a decrease in the production of short-chain fatty acids such as propionate or butyrate. Taken together, these results suggest that the TDIs of the European Food Safety Authority (EFSA) should be reviewed to consider the cocktail effect.