Grant: Project Grant

Our gut is regularly exposed to foods that need to be processed and digested ("metabolism") to provide nutrients necessary for life. The gut also harbors a vast number of microbes, collectively called "microbiota", that are in constant interaction with its host and the ingested food, to maintain the balance between health and disease. Many food components are metabolized by gut bacteria, producing molecules or "metabolites" that affect human health. In this sense, the microbiota behaves as a key additional metabolic organ, degrading and producing essential nutrients for the host. There is growing evidence that when food-microbe interactions are broken, chronic conditions such as inflammatory bowel diseases (IBD) can develop. However, the factors that contribute to break this equilibrium remain unclear. Tryptophan is an essential amino acid, contained in most protein-based foods, that when ingested in the diet can become a source of energy for gut bacteria. Beneficial bacteria, such as certain Lactobacillus, produce tryptophan-derived metabolites called "indoles" that activate protective immune responses in the gut. Patients with IBD have both altered gut microbiota and abnormal tryptophan metabolism, raising the possibility that dysregulated gut bacterial metabolism of tryptophan plays a role in IBD. The general aim of this project is thus, (i) to understand the precise metabolic interactions between gut microbiota and dietary tryptophan and, (ii) to determine whether and how when disrupted, they contribute to inflammation. Our long-term goal is to provide evidence-based dietary recommendations and discover specific probiotic formulations that through indole production can prevent, or help treat, IBD.