(OR22-06-23) Gut Microbes and Dietary Composition Modulate the Production of Blueberry Derived Metabolites

Objectives: Dietary supplementation of blueberries improves cardiovascular health as reported by us and others. Evidence suggests that blueberry components are mostly metabolized in the gut but the studies are limited. In the present study, we investigated the role of gut microbes and the impact of dietary composition in the production of blueberry-derived metabolites.

Methods: 7-week-old male mice consumed a standard diet (C) or a high-fat diet (HF). The subgroups of C and HF received 3.7% freeze-dried wild blueberry powder (~ 1.5 human servings) in their diet (CB and HFB). Further, subgroups of CB and HFB received an antibiotic cocktail in drinking water (CBAb and HFBAb). After 12 weeks of treatment, the following were assessed: metabolic parameters, blueberry-derived metabolites (by high-throughput UPLC-MS/MS), and the composition of gut microbes (by amplifying the V4 region of the 16s rRNA gene).

Results: Blueberry supplementation did not alter metabolic parameters in CB vs C and HFB vs HF mice. The depletion of gut microbes in CBAb and HFBAb mice was confirmed by broth experiments and 16s rRNA amplification. Dietary blueberries increased the plasma levels of 3,4-dimethoxy cinnamic acid, p-coumaric acid, hippuric acid, and total metabolites in CB vs C mice. Antibiotic treatment greatly reduced the levels of these metabolites except p-coumaric acid in CBA vs CB mice indicating the importance of gut microbes in mediating the production of blueberry-derived metabolites. Further, commensal microbes were positively associated with the plasma blueberry metabolites. In the high-fat cohort, dietary blueberries increased the plasma levels of hydroxy hippuric acid, hippuric acid, and total metabolites in HFB vs HF mice indicating the impact of dietary composition on metabolite production. Antibiotic treatment suppressed these metabolites in HFBAb vs HFB.  The differences in the metabolites production between CB and HFB mice could be due to the changes in the composition of gut microbes. Further, high fat diet greatly reduced the efficiency of diet-derived metabolite production.

Conclusions: Our study indicates that a healthy gut microbial environment is essential to metabolize the blueberry bioactive components and to mediate the vascular effects of dietary blueberries.

Funding Sources: NIH-NCCIH and USDA-NIFA