GutStunting

In young children, undernutrition frequently manifests as stunting, which afflicts over 155 million children and contributes to nearly half of the world’s childhood mortality under the age of five. Stunting is postulated to be the consequence of small intestinal dysfunctions. Studies in multiple model systems, including our own in drosophila and mice, have unveiled that gut microbiome components act as critical determinants of growth trajectory and stunting phenotype. Despite these advances, the underlying physiopathology of diet-induced stunting on gut functions and our understanding of how selected gut microbes contribute to such processes and healthy systemic growth remains elusive. This research program aims at identifying the mechanistic basis of this fundamental biological problem: how poor nutrition alters gut functions in the context of juvenile growth and how a selected microbial intervention restores such functions. Our recent results suggest an evolutionary conserved diet-host-microbe dialog at the gut interface shaping host systemic growth and metabolism via an impact on primary intestinal functions (digestion, absorption and release of endocrine signals). Hence, the overall objective of this research program is to capitalize on animal models and human intestinal organoid models to investigate this conserved dialog at the cellular and molecular level. We aim to to identify i) the physio-pathological mechanisms at play in the intestinal epithelium during chronic undernutrition and ii) the physiological mechanisms engaged by a selected gut microbe to restore gut functions supporting healthy juvenile growth and metabolism. Our research program will include a hypothesis-driven part focusing on dissecting the role of gut hormones in the context of juvenile undernutrition and open-ended and comparative approaches to identify novel cellular and molecular mechanisms in the gut influenced by undernutrition and a selected microbial intervention.