Pathological role of D-serine metabolism in microbiota-gut-brain axis dysfunction in intestinal inflammatory disorders. – Daa-Gut

Disturbances at the microbiota-gut-brain axis have been described in chronic intestinal disorders, such as irritable bowel syndrome or inflammatory bowel disease which are associated to anxio-depressive symptoms. Despite many progresses, the signaling pathways involved in this inter-organ dialogue in health and disease are not fully identified. Remarkably, right-handed amino acids (D-AAs) which are metabolized by microorganisms but also directly by the host are emerging as an important class of signaling molecules contributing to brain and peripheral organs homeostasis. Whether D-AAs and particularly D-Serine (D-SER) would support interconnection of microbiota, gut and brain and would play a role in GI disorders and in associated psychiatric symptoms is not known. Based on our preliminary data and on the literature, we make the hypothesis that any primary alteration in D-Ser metabolism in the gut may alter microbiota and then promote a pathogenic trajectory to the development of intestinal inflammation and the associated brain symptoms in both mouse models and in patients. We foresee that rebalancing D-ser metabolism in the gut with new tailored probiotics may circumvent all symptoms. By doing so, DaaGUT ambitions to uncover the roles of D-AAs in microbiota-gut-brain axis dysfunction in intestinal disorders using multiscale approaches and by combining the complementary expertise in neurophysiology, microbiology, gut disease of our four teams.