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<p>Consumption of diets rich in flavonoids reduces the risk of cardiovascular disease. The gut microbiota (i.e., collection of microbes that inhabit our gut) contributes to the beneficial effects of flavonoids by transforming them into more readily absorbable and active metabolites. However, there is a large degree of interpersonal variation in the observed benefits and, evidently, in the nature and extent of these microbial transformations, which remain poorly characterized. Thus, we cannot currently predict the extent to which--if at all--an individual will benefit from the consumption of flavonoids. The overarching goal of this proposal is to define whether interpersonal differences in gut-microbial metabolism of flavonoids modulate the beneficial effects associated with their consumption. We propose to initially focus on anthocyanins and its main microbial-derived metabolite protocatechuic acid (PCA).</p><p>Objective 1: To assess the extent of interpersonal variation in gut microbial conversion of a natural source of mixed anthocyanins in vitro and its relation with microbiota composition and health status.</p><p>Objective 2: To assess whether interpersonal variation in gut microbial metabolism of anthocyanins modulates protective effects of these flavonoids in a gnotobiotic genetic mouse model of atherosclerosis (apo E -/- mice).</p><p>Objective 3: To test effects of PCA-producing and PCA-degrading bacteria in a gnotobiotic genetic mouse model of atherosclerosis (apo E -/- mice).These objectives should be attainable within 3 years and with the support made available to us. </p>
Consumption of diets rich in fruits and vegetables reduces the risk of cardiovascular disease (e.g., atherosclerosis). Some of the health benefits associated with these dietary components are derived from pigments present in plants called flavonoids. However, our bodies do not absorb most flavonoids as they are present in the plants. Flavonoids are metabolined by the trillions of microbes that inhabit our gut (i.e., gut microbiota). Gut microbes contribute to the beneficial effects of flavonoids by transforming them into more readily absorbable and active metabolites. However, there is a large degree of interpersonal variation in the observed benefits and, evidently, in the nature and extent of these microbial transformations, which remain poorly characterized. Thus, we cannot currently predict the extent to which--if at all--an individual will benefit from the consumption of flavonoids. This proposal describes an approach for determining the relationship between interpersonal differences in gut microbial transformations of flavonoids and the beneficial effects associated with their consumption. We will investigate how interpersonal variation in gut microbiota composition affects the protective effects of a specific group of flavonoids. We will transplant human gut microbial communities (i.e., human feces) from healthy subjects and subjects with cardiovascular disease into groups of otherwise identical germ-free mice (i.e., mice that are not colonized with any microbes), and test for causal associations between gut microbial community composition, flavonoid transformations and development of atherosclerosis. Collectively, these studies will provide key insights into the roles of gut microbes in mediating effects associated consumption of flavonoids. Importantly, these results will be used to identify new probiotics that may be given together with anthocyanins to enhance their effects against cardiovascular disease.