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Effets des polluants atmosphériques et alimentaires sur l’inflammation et la dysbiose intestinale

Workpackage : WP1

EQUIPE 

The aim of our team is to highlight environmental risk factors implicated in IBD development or perpetuation.

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Research topics


We set up several mechanistic studies to link potential environmental risk factors to IBD development or perpetuation. We previously demonstrated that oral daily intake of aluminum at a concentration observed in food increased the severity as well as the duration of experimental colitis (Pineton de Chambrun, Mucosal Immunol, 2014). To go further, we performed a toxicological analysis of aluminum effect on human intestinal epithelial cells and showed that aluminum decreased cell viability through apoptosis and reactive oxygen species generation. Transcriptomic analysis argued in favour of pro-tumorigenic and pro-inflammatory effects on intestinal epithelial cells (Djouina et al., Food Chem Tox 2017). As aluminum was observed to increase intestinal permeability, we assessed its potential role in irritable bowel syndrome, an intestinal disorder with a leaky gut as a key feature. We demonstrated that low-doses of aluminum induced visceral hypersensitivity in rats and mice, and reproduced clinical and molecular features of IBS. Indeed, as observed in human, female animals were more sensitive than mice to aluminum, and mechanisms involved mast cells and the proteinase-activated receptor-2 activation (Esquerre et al., Cellular and Molecular Gastroenterology and Hepatology, 2018).

Based on a bibliographic approach, we were interested in the mycotoxin deoxynivalenol (DON), a frequent contaminant of cereals and their by-products. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain could represent a major public health risk. However, despite its well-known acute toxicological effects, information on the adverse effects of realistic exposure remains limited. We showed that mice chronic oral exposure to human relevant doses of DON induced adaptive immune cells activation in the mesenteric lymph nodes, modification of inflammatory parameters in the colon and ileum and gut microbiota dysbiosis. Together, we demonstrated that DON induces several disturbances of gut homeostasis with likely pathological implications for susceptible individuals (Vignal et al., Archives of Toxicology, 2018).

Based on epidemiological results, reporting that exposure to air pollution may be associated with various gastrointestinal diseases including IBD, we aimed to determine the short-term effects of urban coarse particulate matter (PM) inhalation on colonic homeostasis in mice. As accumulating experimental evidence showed that immune responses in the pulmonary and intestinal mucosae are closely interrelated, and that gut-lung crosstalk controls pathophysiological processes such as responses to cigarette smoke and influenza virus infection, we also conducted the analysis on the pulmonary mucosa. We showed that exposure to urban coarse PM in a ventilated inhalation chamber for 15 days at a concentration relevant to episodic elevation peak of air pollution induced systemic oxidative stress, recruited immune cells to the lung, and increased cytokine levels in the lung and colon. We also demonstrated that PM-induced low-grade inflammation in the lung and colon is mediated by oxidative stress. Indeed, concomitant oral administration of the well-known antioxidant N-acetyl-L-cysteine reversed all the observed effects relative to the inhalation of coarse PM (Vignal et al., Particle and Fibre Toxicology, 2017).

 

Publications

 
BBRC2018-Mucin C-mannosylation

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases
Body-Malapel M, Djouina M, Waxin C, Langlois A, Gower-Rousseau C, Zerbib P, Schmidt AM, Desreumaux P, Boulanger E, Vignal C.
Mucosal Immunol 2018 Dec 12. doi: 10.1038/s41385-018-0119-z..

BBRC2018-Mucin C-mannosylation

Aluminum ingestion promotes colorectal hypersensitivity in rodents
Esquerre N, Basso L, Dubuquoy C, Djouina M, Chappard D, Blanpied C, Desreumaux P, Vergnolle N, Vignal-C-Body-Malapel M
Cellular and Molecular Gastroenterology and Hepatology 2018 Sep 20;7(1):185-196. doi: 10.1016/j.jcmgh.2018.09.012.

 
FG PaperJLD 2011 1

Chronic ingestion of deoxynivalenol at human dietary levels impairs intestinal homeostasis and gut microbiota in mice
Vignal C, Djouina M, Pichavant M, Caboche S, Waxin C, Beury D, Hot D, Gower-Rousseau C, Body-Malapel M
Archives of Toxicology 2018 Jul;92(7):2327-2338. doi: 10.1007/s00204-018-2228-6

FG PaperJLD 2011 1

Effects of urban coarse particles inhalation on oxidative and inflammatory parameters in the mouse lung and colon
Vignal C, Pichavant M, Alleman Y L, Djouina M, Dingreville F, Perdrix E, Waxin C, Alami OA, Gower-Rousseau C, Desreumaux P, Body-Malapel M
Particle and Fibre Toxicology 2017 Nov 22;14(1):46. doi: 10.1186/s12989-017-0227-z

FG PaperJLD 2011 1

Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells
Djouina M, Esquerre E, Desreumaux P, Vignal C, Body-Malapel M
Food and Chemical Toxicology 2016 May;91:108-16. doi: 10.1016/j.fct.2016.03.008