Role of Dietary Flavonoid Compounds in Driving Patterns of Microbial Community Assembly.

Flavonoids are a group of polyphenolic dietary compounds found in many different plant-based foods. There is increasing evidence that higher flavonoid intake may be causally linked to a reduced risk of cardiovascular disease and other chronic diseases. The bioactivity and bioavailability of many dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. However, the role that habitual flavonoid intake plays in shaping the human gut microbiome is poorly understood. We describe an application of an ecosystem-based analytic approach to nutritional, microbiome, and questionnaire data from a cohort of more than 240 generally healthy adult males to assess the role of dietary flavonoid compounds in driving patterns of microbial community assembly. We identified six subclass-specific microbial communities (SMCs) uniquely and independently associated with intakes of the six flavonoid subclasses. Eggerthela lenta was positively associated with intakes of flavonol and flavanone, and Adlercreutzia equolifaciens was positively associated with intakes of flavonols and flavanol monomers. In contrast, for nearly all flavonoid subclasses, Flavonifractor plautii was inversely associated with subclass consumption. Consuming tea at least once per week explained 10.4% of the total variance in assembly of the 20 species comprising the flavanol monomer SMC. The novel methodology employed, necessitated by multidimensional microbiome data that consist of nonindependent features that exhibit a wide range of distributions and mean values, addresses a major challenge in our ability to understand associations of the microbiome in a wide range of clinical and epidemiologic settings.IMPORTANCE Dietary flavonoids, which have been implicated in lowering chronic disease risk and improving blood pressure, represent a diverse group of polyphenolic compounds found in many commonly consumed foods such as tea, red wine, apples, and berries. The bioactivity and bioavailability of more dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. With demonstrated prebiotic and antimicrobial effects in in vitro and in animal models, it is surprising that there are not many human studies investigating the role dietary flavonoids play in shaping the gastrointestinal microbiome. Our analysis revealed patterns of community assembly that uniquely and independently characterize an individual's exposure to various flavonoid compounds. Furthermore, this study confirmed, independent from effects of other dietary and lifestyle factors included in the multivariate-adjusted model, that flavonoid intake is associated with microbial community assembly.

Association of flavonoid-rich foods and flavonoids with risk of all-cause mortality.

Flavonoids are bioactive compounds found in foods such as tea, red wine, fruits and vegetables. Higher intakes of specific flavonoids, and flavonoid-rich foods, have been linked to reduced mortality from specific vascular diseases and cancers. However, the importance of flavonoid-rich foods, and flavonoids, in preventing all-cause mortality remains uncertain. As such, we examined the association of intake of flavonoid-rich foods and flavonoids with subsequent mortality among 93 145 young and middle-aged women in the Nurses' Health Study II. During 1 838 946 person-years of follow-up, 1808 participants died. When compared with non-consumers, frequent consumers of red wine, tea, peppers, blueberries and strawberries were at reduced risk of all-cause mortality (P<0·05), with the strongest associations observed for red wine and tea; multivariable-adjusted hazard ratios 0·60 (95 % CI 0·49, 0·74) and 0·73 (95 % CI 0·65, 0·83), respectively. Conversely, frequent grapefruit consumers were at increased risk of all-cause mortality, compared with their non-grapefruit consuming counterparts (P<0·05). When compared with those in the lowest consumption quintile, participants in the highest quintile of total-flavonoid intake were at reduced risk of all-cause mortality in the age-adjusted model; 0·81 (95 % CI 0·71, 0·93). However, this association was attenuated following multivariable adjustment; 0·92 (95 % CI 0·80, 1·06). Similar results were observed for consumption of flavan-3-ols, proanthocyanidins and anthocyanins. Flavonols, flavanones and flavones were not associated with all-cause mortality in any model. Despite null associations at the compound level and select foods, higher consumption of red wine, tea, peppers, blueberries and strawberries, was associated with reduced risk of total and cause-specific mortality. These findings support the rationale for making food-based dietary recommendations.

Tea and non-tea flavonol intakes in relation to atherosclerotic vascular disease mortality in older women.

Epidemiological studies have indicated that dietary flavonoids generally, and flavonols specifically, may contribute to cardiovascular health. Tea consumption, which is often the main dietary source of flavonoids and flavonols, is associated with a reduced risk of cardiovascular outcomes. The primary objective of the present study was to explore the association of the habitual intake of flavonols from tea and non-tea sources with the risk of atherosclerotic vascular disease mortality in a population of elderly women. A total of 1063 women, aged over 75 years, were randomly selected from ambulant Caucasian women living in Perth, Western Australia. Flavonoid consumption was assessed using the US Department of Agriculture Flavonoid, Flavone and Proanthocyanidin databases. Atherosclerotic vascular disease mortality was assessed over 5 years of follow-up through the Western Australian Data Linkage System. During the follow-up, sixty-four women died from atherosclerotic vascular disease. Women in the highest compared with the lowest tertile of flavonol intake had a lower risk of atherosclerotic vascular disease death (OR 0·27, 95 % CI 0·13, 0·59; P≤ 0·01 for trend in multivariate-adjusted models). Similar relationships were observed for flavonol intake derived from both tea (OR 0·38, 95 % CI 0·18, 0·79; P< 0·01) and non-tea (OR 0·41, 95 % CI 0·20, 0·85; P= 0·05) sources. Tea was the main contributor to flavonol intake (65 %), and the intakes of flavonols from tea and non-tea sources were not significantly correlated. In conclusion, increased consumption of flavonols was independently associated with a lower risk of atherosclerotic vascular disease mortality. Both tea and non-tea sources of flavonols were independently associated with this benefit.