Impacts of chronic intoxication by Bt k bioinsecticides on the intestinal homeostasis and the immune response: from insects to mammals – ImBio

Cry toxins produced by Bacillus thuringiensis (Bt) are becoming widely used worldwide as bioinsecticides or in genetically modified crops (GMC) to fight lepidopteran, coleopteran and dipteran pests in organic farming, forestry and mosquito control. Moreover, with recent incentives, such as Plan Ecophyto 2018 in France, their use as an alternative to chemical pesticides (that must be reduced by 50%) will further increase in the next decades. The question now is how far organisms will be potentially impacted by the resulting augmentation of the Bt bacterium and its Cry toxins in the environment. Although the specificity of the acute toxicity of these toxins has been proved since many years, with no acute toxicity observed towards non-target species ranging from honey bees to human, data are scarce on adverse effects that could result from chronic exposure.
We know that the main mode of contamination of the organisms by Bt toxins is the digestive tract and that these bioinsecticides are made up of bacteria that may stimulate and/or affect the immune response. Moreover, our preliminary unpublished data show that the bioinsecticide Bt kurstaki (producing 6 different toxins) impairs the physiology of Drosophila melanogaster gut with a reduction of the local immune response and a perturbation of the gut homeostasis. Regarding health aspects, our project will therefore focus on the impact of chronic exposure to Bt toxins on both the gut homeostasis and the immune response. At first, we will decipher the mechanisms underlying the defective gut homeostasis we observed. Although acute toxicity of Cry toxins is due to their binding on known receptors at the surface of the intestinal epithelium leading to the lysis or death of cells, we have no clue about the mechanisms involved in the adverse effects on non-target organisms. This approach will be carry out in parallel on the D. melanogaster and Sus scofra models. Second, we want to understand which mechanisms are involved in the inhibition of the local gut immune response provoked by the ingestion of the Bt bioinsecticide. Again the drosophila and pig models will be suitable for this study. Third, as the local immune response is altered, we can assume that the systemic immune response may be affected as well. We will use D. melanogaster and D. suzukii (a pest) to monitor the impact of chronic exposure to Bt toxins on cellular (hemocytes) and humoral (phenol-oxidase) components of immunity. Fourth, we will study the consequences of a defective immune response caused by Bt exposure on the capability of an organism (D. melanogaster and D. suzukii) to resist to a super-infection (Escherichia coli, Erwinia carotovora, Beauveria bassiana) or to parasitism (Leptopilina spp. and Asobara spp.) and the resulting ecotoxicological consequences. In parallel, we will estimate the direct and indirect impact of Bt toxins on non-target insect parasitoids, largely used in biological control, and how it can affect the ecosystem. Finally, we will integrate, in all of these studies, the synergistic impacts that may occur between Bt bioinsecticides and toxics which are already present in our diets or in the environment: the mycotoxin deoxynivalenol (from fusarium fungus) and the synthetic insecticide deltamethrin.
Thanks to the complementary models we use (e.g. drosophila and pig) and the diversity of approaches we undertake (molecular, cellular, genetic and ecotoxicologic), our project integrates the impacts of Bt bioinsecticides on both the animal/human health (axe thématique 2) and on the ecosystem (axe thématique 3).