Unveiling the gut's sensory code: Implications for food, development, and disease

PROJECT SUMMARY This research aims to revolutionize the understanding of nutrition by investigating the concept of "nutritional memory," which posits that early-life dietary experiences create lasting impressions on gut neuropod cells that influence lifelong food choices and consumption patterns. This paradigm shift challenges the traditional calorie-centric view and proposes that the gut acts as a sensory organ, communicating vital nutrient information to the brain. The research will be conducted in three parts: 1) Characterization of the sensory landscape of gut neuropod cells, utilizing calcium imaging and electrophysiology to identify and profile nutrient receptors; 2) Elucidation of the role of long-lived neuropod cells in shaping food preferences, analyzing how early-life dietary exposure influences their transcriptome, epigenome, and proteome; and 3) Establishment of causality and exploration of therapeutic potential by ablating long-lived neuropod cells and assessing the impact on food preferences and metabolic health. The potential outcomes of this research are transformative, including: 1) identification of the molecular mechanisms underlying nutritional memory, 2) development of innovative interventions to reprogram unhealthy food preferences and combat diet-related diseases, and 3) establishment of new dietary guidelines for pregnant women and infants to reduce health disparities. The investigator is uniquely positioned to undertake this ambitious project, with a strong technical and conceptual foundation, a team of world-renowned experts, and a collaborative approach to unravel the mysteries of gut sensory memory and create a healthier future for generations to come.