Consequences of early life host-microbial mutualism on inflammatory bowel diseases

The etiology of Inflammatory Bowel Disease (IBD) is unknown. Epidemiological and experimental studies report an association between early life events and the susceptibility to develop IBD later in life. Indeed, reduced contact with gut microbiota early in life can program the immune system toward increased susceptibility to develop gut inflammation later in life, an immune memory phenomenon termed “pathological imprinting.” However, the underlying mechanisms and the nature of pathological imprinting remain unclear. The goal of this project is to understand how the dietary change in fat/fiber amounts early in childhood affects gut microbiota establishment, the intestinal mucosal homeostasis and the susceptibility to develop colitis. We will take the advantage of advanced high-throughput sequencing and mouse models harbouring controlled microbiota to uncover the cellular and molecular mechanisms underlying pathological imprinting. Since in high-income countries, the dietary predilection to western-style diets rich in fats parallels an increase in IBD incidence, the results of this project will propel future studies aimed at preventing IBD development in individuals at high risk of developing this debilitating disease.