Abstract IA15: The microbiome and its association with human metabolism and adiposity.

Abstract

Abstract The rise in obesity and inflammation-based disease is striking across all socioeconomic levels at alarming rates. Over the past 30 years in the U.S., adults and children have experienced a marked increase in the prevalence of overweight and obesity. Two-thirds of American adults are obese or overweight. Among adults aged 20-74 years, the prevalence of obesity increased from 15.0% to 32.9%. Obesity-related disease risk has also been on the rise although there is some variation among individuals. Environmental and host genetic factors may account for some of the variation in disease risk seen among individuals. Recently, the human gut microbial community (GMC) has been identified as a possible factor that may alter host metabolism and adiposity. The Human Microbiome Project, a part of NIH's recent Roadmap for Medical Research, opened new avenues to study the gut microbiome (i.e., all the microbial genomes and their genes) as a modifiable environmental factor that influences human health. New molecular methods, that do not require culturing bacteria, have uncovered high within- and between-individual gut microbial diversity. The highly diverse gut microbiome contains many metabolic pathways that alter dietary constituents and affect human health in both positive and negative ways. Thus, inter-individual variation in disease risk may be, in part, associated with the gut microbiome. The GMC is tightly associated with host energy metabolism and provides a mechanistic link between human health and exposures. Energy use and adiposity are influenced by a tight and coordinated connection between dietary intake, the GMC, and the host. The metabolism of diet by the microbiome is complex and is associated with the metabolic capability of specific bacterial members in the gut community often arranged in consortia or networks of micro-organisms. The recent characterization of bacterial enterotypes, based on molecular analyses of the GMC, suggests that networks of microbial species have redundant metabolic pathways which provide about 10% of the host nutrition by the metabolism of diet. For example, the gut microbiome alters energy storage through the metabolism of dietary carbohydrates to short chain fatty acids (SCFA). In turn, the SCFA from bacterial metabolism influence pathways of carbon metabolism and fat storage in the human host. Mechanisms by which the gut microbiome influences human metabolism and subsequent disease risk include: regulation of energy uptake from diet, interaction with signaling molecules involved in host metabolism, modification of gut permeability, and sub-chronic inflammation, a hallmark of obesity-related diseases. In addition, recent studies in humans and mice suggest that the host genotype may exert some control on the composition of the gut microbiome and attenuate obesity-related diseases. These pathways give insight into the multiple ways through which the gut microbiome may influence adiposity and disease risk. Citation Format: Meredith A. J. Hullar. The microbiome and its association with human metabolism and adiposity. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA15.