Grape polyphenols reduce fasting glucose and increase hyocholic acid in healthy humans: a meta-omics study.

Grape polyphenols (GPs) are rich in B-type proanthocyanidins, which promote metabolic resilience. Longitudinal metabolomic, metagenomic, and metaproteomic changes were measured in 27 healthy subjects supplemented with soy protein isolate (SPI, 40 g per day) for 5 days followed by GPs complexed to SPI (GP-SPI standardized to 5% GPs, 40 g per day) for 10 days. Fecal, urine, and/or fasting blood samples were collected before supplementation (day -5), after 5 days of SPI (day 0), and after 2, 4 and 10 days of GP-SPI. Most multi-omic changes observed after 2 and/or 4 days of GP-SPI intake were temporary, returning to pre-supplementation profiles by day 10. Shotgun metagenomics sequencing provided insights that could not be captured with 16S rRNA amplicon sequencing. Notably, 10 days of GP-SPI decreased fasting blood glucose and increased serum hyocholic acid (HCA), a glucoregulatory bile acid, which negatively correlated with one gut bacterial guild. In conclusion, GP-induced suppression of a bacterial guild may lead to higher HCA and lower fasting blood glucose.