(P26-023-25) Exploring the Role of Gut Microbiome in Mediating Endothelial Function Improvements With Blueberry Consumption: Insights From Fecal Microbiota Transplant in Germ-Free Mice

Objectives: We previously demonstrated that 12 weeks of daily blueberry consumption improved endothelial function in postmenopausal women with above-normal blood pressure. Using a gnotobiotic mouse model, this study explored whether blueberry-induced gut microbiome changes mediate endothelial function improvements.

Methods: Male C57BL/6J germ-free (GF) mice received fecal microbiota transplant through oral gavage with pooled inoculum from postmenopausal women with above-normal blood pressure before or after the 12-week blueberry intervention. Transplants comprised pooled fecal material from the responder cohort before blueberry intervention (Pre-Blueberry) and after 12 weeks of daily blueberry consumption (Post-Blueberry). We hypothesized donor vascular phenotypes would be transferred to the recipient mice.

Results: Results showed no differences in endothelial-mediated dilation (Pre-Blueberry: 372.2±20.6, Post-Blueberry: 417.9±15.6 AUC; p=0.6778), pulse wave velocity (Pre-Blueberry: 437.8±15.3, Post-Blueberry: 438.3±17.1 cm/s; p=0.0890), or intrinsic stiffness (Pre-Blueberry: 2350±256.6, Post-Blueberry: 2126±269.6 kPa; p=0.6000).

Conclusions: These results suggest that microbiome composition alone may not be sufficient to recreate vascular phenotypes in this model; rather, the observed outcomes may be more reliant on blueberry-microbiome interactions. This is supported by complementary experiments where mice were colonized with the same inoculum as described but were gavaged with 116.1 mg of freeze-dried blueberry powder. Results demonstrated plasma levels of bioactive blueberry polyphenol metabolites differed according to microbiome composition. Furthermore, there were varied responses to blueberry intervention within the human population, and while there were no microbiota shifts with blueberry exposure in the primary analysis, we did observe differences in microbiota composition in a sub-group analysis of endothelial function responders compared to non-responders. Collectively, this research indicates future studies should focus on exploring microbial signatures associated with increased exposure of blueberry-derived bioactive compounds.

Funding Sources: USDA National Institute of Food and Agriculture [grant no. 2020-67017-30833/project accession no.1021875] and the US Highbush Blueberry Council.