Poorly absorbed fruit polyphenols are associated with metabolic resilience raising questions about their mechanisms of action. We previously demonstrated that C57BL/6 mice fed high-fat diet supplemented with grape polyphenols (GP) for 12 weeks resulted in a bloom of Akkermansia muciniphila in association with changes in gut gene expression consistent with attenuated metabolic syndrome symptoms. Here we investigated the timing of GP-induced effects and identified the main class of GP responsible for the A. muciniphila bloom. In two 14-day time course studies mice were fed high- or low-fat diets (HFD, LFD) or isocaloric ingredient-matched formulations supplemented with 1% grape polyphenols (HFD-GP, LFD-GP). Mice fed HFD-GP for two weeks showed significantly improved oral glucose tolerance (OGT) compared to control, while LFD and LFD-GP groups displayed similar OGT. A. muciniphila bloom was detected earlier in mice fed LFD-GP than HFD-GP; however, difference in timing of this GP-induced bloom was more dependent on baseline abundance of A. muciniphila in the two cohorts of mice than on dietary fat and this was confirmed in additional experiments. The GP-induced bloom in A. muciniphila occurred before specific intestinal gene expression changes associated with metabolic resilience. Finally, compared to vehicle, mice dosed for 10 days with GP extract (GPE) or an equivalent dose of purified oligomeric grape proanthocyanidins (PAC) showed similar increases in fecal and cecal A. muciniphila. These data suggest that PAC-induced modification of the gut microbiota precedes changes in host gene expression and phenotypes associated with metabolic health.

Grape proanthocyanidin-induced bloom of gut microbe Akkermansia muciniphila precedes intestinal gene expression changes associated with metabolic resilience

254th National Meeting (2017)

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