Investigating the Interactions of the Gut Microbiome, Metabolism, and Hormones in Individual Dietary Responses: A Pathway to Personalized Nutrition

Abstract

The global rise in lifestyle-associated cardiometabolic diseases calls for personalized nutritional strategies to address highly variable individual responses to dietary interventions. This thesis investigated the complex interactions between diet, the gut microbiome, metabolism, and hormones. By evaluating individual responses to two plant-based dietary patterns—a Nordic diet and a Vegetarian diet—in a cohort with elevated cardiometabolic risk using integrative multi-omics analyses, this research identified distinct baseline and diet-induced signatures that separate "Responders" from "Non-Responders" as defined based on their LDL-cholesterol changes. Notably, a cross-over trial proved that participants classified as “Non-Responders” to one diet could successfully achieve Responder status when transitioned to the alternative diet. Additionally, this work demonstrated that glucose tolerance may fluctuate across the menstrual cycle, with emerging evidence suggesting that the gut microbiome may influence this association. Moreover, this thesis provides evidence that postprandial GLP-1 secretion is altered by metabolic conditions (such as diabetes and overweight) and is strongly influenced by meal composition. Ultimately, these findings show that utilizing multi-omics signatures and accounting for hormonal variations may significantly improve the effectiveness of targeted dietary interventions, offering a powerful tool for personalized disease prevention and health optimization.