Diet-induced alterations to postprandial metabolism and the gut microbiota

Abstract

Obesity is a key component of a cluster of metabolic risk factors for chronic disease which include dyslipidemia, hyperglycemia, and hypertension. Stark changes in diet and lifestyle contribute to growing metabolic disorder prevalence. Many Americans regularly consume foods low in fiber and rich in fat and sugar, which can negatively influence glucose and lipid metabolism over time. A nutritionally poor diet exerts deleterious effects on the gastrointestinal microbial community which has larger host health implications. As a modifiable risk factor, diet can be part of the solution to counter the rise of chronic disease. However, dietary responses as it pertains to glucose and lipid metabolism display high interindividual variability. This interindividual variability with diet can also be observed at the microbial level in our gastrointestinal system. In metabolically at-risk adults, we examined postprandial responses and the efficacy of a long-term lentil dietary intervention in improving postprandial glycemic responses. We further assessed the effect of an antioxidant-rich juice from the Aronia melanocarpa berry and its anti-inflammatory potential against a high fat diet in a gnotobiotic mouse model to evaluate how specific gut microbial communities transferred from metabolically at-risk adults with different inflammatory profiles may impact dietary responses. Postprandial triglyceride responses in adults with overweight and obesity can be partially explained by central adiposity, insulin resistance, and the ability to switch between glucose and fat metabolism to a metabolic stress. A long-term dietary intervention with lentils, a fiber-rich pulse crop, worked in a dose-dependent manner to reduce insulin resistance in adults with increased central adiposity without an increase in gastrointestinal symptoms, a common deterrent to incorporating fiber-foods in the diet. Our gnotobiotic mouse experiments revealed donor- dependent changes in dietary responses. We observed protective effects of Aronia juice in mice, particularly in mice from the low inflammation stool donor. Metabolomic changes in phospholipids such as phosphatidylcholine and sphingomyelin were further detected, with changes respectively unique to Aronia juice and high-fat diet. Taken together, this dissertation provides an improved understanding of our metabolic responses and microbial alterations to the foods we consume, and how these responses influence the progression of metabolic diseases.