FLAXSEED EFFECTS ON GUT MICROBIAL METABOLISM AND CIRCULATING INFLAMMATION-RELATED METABOLIC PROFILES IN AFRICAN AMERICAN AND NON-HISPANIC WHITE WOMEN

Gut microbial dysbiosis has been associated with alterations in production of immune and inflammatorycytokines and other circulating metabolites contributing to inflammation. Gut microbial composition andfunction are amenable to modification by diet. Flaxseed (FS), a whole food commonly consumed as a dietaryadjuvant for several purported health effects, is a rich source of the polyphenolic lignans. Structurally similar toendogenous estrogens, lignans have been most widely studied for phytoestrogen effects; however, anti-inflammatory, immunomodulatory, and antioxidant effects have also been reported, primarily in animal and cellmodels. Importantly, to become physiologically available to humans, plant lignans require metabolism toenterolignans by a consortium of gut microbial community members, but not all individuals are enterolactoneproducers. Plant lignans are converted by the gut bacteria to the primary circulating enterolignanenterolactone (ENL) which can be measured in most body fluids. ENL has been inversely associated withseveral inflammation-related chronic diseases and, as a bacterial metabolite, has significant potential to impacthealth. Using existing data and specimens from a completed flaxseed intervention study in healthy,postmenopausal African American (AA) and non-Hispanic White (NHW) women that investigated the impact ofthe intervention on gut microbial communities, lignan metabolism, and steroid hormone metabolism, we willaccomplish the following Aims: 1) In the overall study sample, determine associations between gut microbialcommunity profiles, circulating metabolic profiles, and circulating inflammation-related cytokines for womenwho are high vs low ENL producers; 2) In a subset of women (n=80; 40 high producers [20 AA, 20 NHW], 40low producers [20 AA, 20 NHW]), utilize metatranscriptomics to a) characterize the impact of the FSintervention on pre- and postintervention microbial gene expression, b) determine associations betweenmicrobial gene expression and circulating metabolites and inflammation-related cytokines, and c) how theseassociations differ by producer status and race; and 3) In the subset of women in Aim 2, utilize fecalmetabolomics to characterize microbial metabolic profiles pre- and post-intervention, and determineassociations with microbial gene expression (metatranscriptomics), circulating metabolites, and inflammation-related cytokines. We hypothesize that the FS intervention will modify microbial gene expression andmetabolic pathways related to chronic low grade inflammation and these pathways will differ by producerstatus and for AA and NHW women. The proposed study offers a unique opportunity to characterize changesin microbial function and subsequent modification of circulating metabolic profiles related to chronic low gradeinflammation in a generous sample of AA and NHW white women. Given the higher incidence of inflammationrelated chronic disease in AA, this study will contribute significantly to our understanding of the role of themicrobiome in inflammatory metabolic processes.