Microilcs: deciphering how the gut microbiota influences innate lymphoid cells in obesity""
Obesity reaches epidemic proportions and currently represents a significant public health challenge. Curbing the prevalence of obesity is one health policy priority, whose achievement requires more effective preventive measures. A high-caloric diet and sedentary lifestyle are key determinants of obesity. The diet shapes gut microbiota composition, which may partly explain why microbiota alterations are associated with an obese phenotype in humans. These microbial alternations have been proven to contribute to energy metabolism and fat storage. This evidence has represented an unprecedented shift in the way we envision obesity management. However, translating this knowledge into microbiota modulation strategies that can be applied in the clinical setting needs a better understanding of the active players within the gut ecosystem, as well as, of the mechanisms underlying their dialog with the host. Preclinical studies show that the microbiota shapes immune responses beyond the intestine with consequences for metabolic health. This proposal aims to decipher the regulatory role of indigenous intestinal bacteria on the recently discovered innate lymphoid cells (ILCs). To achieve this goal, we will use the collection of intestinal human bacteria created in the context of the EUproject MyNewGut by the host institution, first, to identify those with ILCs stimulatory properties and second, to perform mechanistic studies in wild-type and mutant murine models of diet-induced obesity coupled to in vitro experiments with primary cell cultures. Overall, the objective of the MicroILCs proposal is to move forward in the understanding of the mechanisms whereby the gut microbiota controls the immune response to high-energy diets and affects the metabolic phenotype.