Evaluating whether chronic food intake of Bacillus thuringiensis biopesticides promotes bowel diseases

- R. ROUSSET -

Our project is investigating the unintended effects of the most widely used microbial pesticide in agriculture, which is based on spores of the bacterium Bacillus thuringiensis.

bathubow
bathubow To evaluate whether chronic Bt consumption could trigger inflammatory bowel diseases
 

Academy 3 highlight

Our work will help determine whether health measures are needed to prevent consumer exposure, such as longer pre-harvest intervals or thorough washing of fruits and vegetables. Our project assesses the “risks of agricultural products and practices to both biodiversity and human health” and is therefore in line with Academy 3 priorities.

The project

Bacillus thuringiensis (Bt), a spore-forming Gram-positive bacterium, is the leading microbial pesticide used in both organic and conventional agriculture, making it the second most widely used pesticide in the world. Commercial Bt pesticides, which consist of Bt spores that produce entomopathogenic toxins (called Cry toxins), kill target pests after ingestion by destroying their intestinal epithelium. Although studies have shown that Bt spores and toxins are not acutely toxic for non-target organisms over a short period of time, the potential adverse effects of chronic ingestion have not been studied. It is now established that the microbial population colonizing the intestine plays a central role in the development of potential inflammatory bowel diseases (IBD) and cancer. In addition, Bt belongs to the Bacillus cereus group, which is responsible for many foodborne outbreaks in humans. To our knowledge, no study has examined the impact of Bt product consumption on IBD and bowel cancers. The aim of our project is to assess whether chronic ingestion of Bt pesticides promotes or aggravates intestinal diseases. We have been using Drosophila melanogaster, a non-target organism of Bt and a valuable model for studying the impact of Bt pesticides on insects, which are known to be important for environmental health. In addition, the conservation of intestinal physiology between Drosophila and vertebrates will facilitate the transfer of knowledge to the mouse, which is a preclinical model.
We have developed a simple, direct protocol for chronic ingestion of Bt spores that mimics natural dietary exposure to an agricultural dose. Our results show that long-term consumption of Bt-contaminated food, even at low doses, significantly reduces the lifespan of Drosophila. Our findings demonstrate that Bt spores affect gut morphology, promote dysplasia, alter septate junctions and enhance epithelial permeability. They also show that Bacillus spores germinate in the gut and that the number of vegetative cells remains constant. Additionally, we observed increased levels of inflammatory signaling pathways and reactive oxygen species. Overall, our results indicate that chronic consumption of Bt spores promotes inflammation and oxidative stress, leading to premature aging of the gut and early lethality in Drosophila.


 
bathubow
bathubow Intestinal stem cells (green) surrounded by enterocyte nuclei (blue)

The +

Extended to non-target insects, which account for 85% of animal biodiversity, our study suggests that highly persistent Bt spores may have unintended long-term effects on the environment.

What’s next?

Based on our results, we will extend this study to include at-risk individuals who are predisposed to, or develop, intestinal inflammation (IBD) or tumors and may be even more sensitive to Bt. We will also translate our findings to the mouse model. To this end, we have developed a collaboration with Benoit Chassaing’s team (Institut Pasteur), whose members are experts in mucosal microbiota in chronic inflammatory diseases and have studied them using the mouse model.


 

Project information

Scientific domain
Environmental and Human Health, Biology
Key words
Bacillus thuringiensis
Gut inflammation
Drosophila
Mouse
Total budget
€865,000, including €6,000 from Academy 3
Students involved
Aurélia Joly (PhD)
Jade Finkelstein (PhD)
Tiffany Marson (Master)                                                                                                                         
Partners

ISA - Université Côte d’Azur, CNRS, INRAE
Institut Pasteur


 
Project members
Aurélia Joly
Julie Soltys
Jade Finkelstein
Audrey Amate
Marie-Paule Nawrot-Esposito
Alexandra Brun-Barale
Tiffany Marson
Benoit Chassaing
Armel Gallet
Raphaël Rousset


Raphaël Rousset

ISA - Université Côte d’Azur, CNRS, INRAE

Scientific promotion of the project

Oral Presentation:
  • Colloquium « Une Seule Santé » – February 9 and 10, 2023, Paris La Défense - France

Two Posters :

  • 27th European Drosophila Research Conference – October 20-23, 2023, Lyon - France
  • 34th French Drosophila Meeting – October 9-12, 2022, Sète - France