Conférence scientifique | Centre de recherche du CHU Sainte-Justine
Conférence d'Eran Segal, PhD, professeur, Département d'informatique et de mathématiques appliquées, Institut Weizmann des Sciences
Résumé :
Accumulating evidence supports a causal role for the human gut microbiome in obesity, diabetes, metabolic disorders, cardiovascular disease, and numerous other conditions, including cancer. Here, I will present our research on the role of the human microbiome in health and disease, aimed at developing personalized medicine approaches that combine human genetics, microbiome, and nutrition.
In one project, we set out to understand personal variation in the glycemic response to food, tackling the subject of personalization of human nutrition, a poorly studied topic that is critical for human health and to billions of people predisposed to, or suffering from, obesity, T2D and related co-morbidities. We assembled a 1,000 person cohort and measured blood glucose response to >50,000 meals, lifestyle, medical and food frequency questionnaires, blood tests, genetics, and gut microbiome. We showed that blood glucose responses to meals greatly vary between people even when consuming identical foods; devised the first algorithm for accurately predicting personalized glucose responses to food based on clinical and microbiome data; and showed that personalized diets based on our algorithm successfully balanced blood glucose levels in prediabetic individuals. These results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences.
I will also present our studies of the mechanisms driving recurrent post-dieting obesity in which we identified an intestinal microbiome signature that persists after successful dieting of obese mice. This microbiome signature contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions and transmits the accelerated weight regain phenotype upon inter-animal transfer. These results thus highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.
Finally, we studied the relative contribution of host genetics and environmental factors in shaping human gut microbiome composition. To this end, we examined genotype and microbiome data in over 1,000 healthy individuals from several distinct ancestral origins who share a relatively common environment, and demonstrated that the gut microbiome is not significantly associated with genetic ancestry. In contrast, we find significant similarities in the microbiome composition of genetically unrelated individuals who share a household, and show that over 20% of the gut microbiome variance can be explained via environmental factors related to diet, drugs and anthropometric measurements. We define the term biome-explainability as the variance of a host phenotype explained by the microbiome after accounting for the contribution of human genetics. Consistent with our finding that microbiome and host genetics are largely independent, we find significant biome-explainability levels of 24%-36% for several human traits and disease risk factors. We also successfully replicated our results in an independent Dutch cohort. Overall, our results suggest that human microbiome composition is dominated by environmental factors rather than by host genetics.
