The importance of the intestinal microbiota for the physiology of the host and its involvement in the development of physio-pathological phenomena are increasingly recognised. In this context, our research focuses on the study of the gut microbiota-food interaction as a factor of vulnerability to the development of human pathologies. Our studies therefore lie at the interface between microbiology, nutrition and physiopathology, and mainly use preclinical models, including microbiota transplants to germfree or specific-pathogen free rodents. Pathologies we consider include psychiatric diseases (anxiety and depression, autism, eating disorders…), metabolic diseases (obesity, diabetes, liver diseases) as well as colon cancer, atherosclerosis. The team’s two main areas of research currently focus on :
The aim of our projects is to understand how the association between food and intestinal microbiota can be a factor in the onset of the pathologies under study, to identify the mechanisms involved and thus open up new therapeutic or preventive avenues based on modulation of the intestinal microbiota.
Sugars are largely present in the Western diet and their role in the development of metabolic disease is now well recognized. However, the interactions between sugar and the microbiota have been poorly explored. We have conducted studies leading to significant advances in the effects of fructose malabsorption, in particular by showing that fructose reaching the colon can modify the composition and metabolism of the microbiota, thereby stimulating the production of cholecystokinin (CCK) by enteroendocrine cells. We also aim to identify the mechanisms involved in the appearance of visceral hypersensitivity associated with fructose malabsorption in the context of irritable bowel syndrome, taking into account the central role played by the microbiota.
Alongside the numerous studies carried out in recent years on the role played by the intestinal microbiota in the development of obesity and metabolic syndrome, studies have also suggested the involvement of the intestinal microbiota in associated liver disease. These liver diseases, grouped together under the name NAFLD (non-alcoholic fatty liver disease), constitute a real public health problem in industrialised countries. Using fecal transplants from mice or human, we have demonstrated a causal role for the microbiota to these liver diseases. We have also identified protective or aggravating bacterial species and aim at deciphering the mechanisms involved.
It is now acknowledged that the gut microbiota plays a role in the gut-brain axis, leading to the concept of a microbiota-gut-brain axis. Our primary interest is on the effect of gut microbiota metabolites on adult brain and behaviour. To this end, we use adult gnotobiotic rodent models whose gut microbiota is manipulated to produce specific metabolites. We thus showed that an overproduction of indole by the gut microbiota leads to anxiety and depression-like behaviours in rats and mice, likely through secondary metabolites crossing the blood-brain barrier and through stimulation of the vagus nerve. Furthermore, a case-control study in humans showed that individuals whose gut microbiota produced a high quantity of indole were at a higher risk of suffering from a poor mood.
Recently, we started studying the role of the gut microbiota in neurodevelopment. In the European Gemma (Genome, Environment, Microbiome and Metabolome in Autism) project, we are conducting fecal transplantation experiments from children with autism to germfree mice in order to decipher the potential association between microbiota, immune function and autism. In the ORION (Impact of indole metabolites produced by the gut microbiota on brain development) project, we manipulate the gut microbiota of rodent pups to produce different profiles of indole metabolites and we examine the consequences on brain and behaviour.
All the team publications are available in the AMIPEM-MICALIS HAL collection.
