Grape proanthocyanidin-induced intestinal bloom of Akkermansia muciniphila is dependent on its baseline abundance and precedes activation of host genes related to metabolic health

J Nutr Biochem. 2018 Jun:56:142-151. doi: 10.1016/j.jnutbio.2018.02.009. Epub 2018 Feb 15.


We previously showed that C57BL/6J mice fed high-fat diet (HFD) supplemented with 1% grape polyphenols (GP) for 12 weeks developed a bloom of Akkermansia muciniphila with attenuated metabolic syndrome symptoms. Here we investigated early timing of GP-induced effects and the responsible class of grape polyphenols. Mice were fed HFD, low-fat diet (LFD) or formulations supplemented with GP (HFD-GP, LFD-GP) for 14 days. Mice fed HFD-GP, but not LFD-GP, showed improved oral glucose tolerance compared to controls. A. muciniphila bloom occurred earlier in mice fed LFD-GP than HFD-GP; however, timing was dependent on baseline A. muciniphila levels rather than dietary fat. Mice gavaged for 10 days with GP extract (GPE) or grape proanthocyanidins (PACs), each delivering 360 mg PACs/kg body weight, induced a bloom of fecal and cecal A. muciniphila, the rate of which depended on initial A. muciniphila abundance. Grape PACs were sufficient to induce a bloom of A. muciniphila independent of specific intestinal gene expression changes. Gut microbial community analysis and in vitro inhibition of A. muciniphila by GPE or PACs suggest that the A. muciniphila bloom in vivo occurs via indirect mechanisms.

Keywords: Akkermansia; Grape; Gut; Microbes; Polyphenols; Proanthocyanidins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Diet
  • Diet, High-Fat*
  • Dietary Fats / pharmacology
  • Dietary Supplements
  • Gastrointestinal Microbiome / drug effects
  • Glucose Tolerance Test
  • Inflammation / metabolism
  • Intestines / drug effects*
  • Liver / metabolism
  • Male
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / chemistry
  • Polyphenols / pharmacology*
  • Proanthocyanidins / pharmacology*
  • RNA, Ribosomal, 16S / genetics
  • Soybean Proteins / chemistry
  • Verrucomicrobia / growth & development*
  • Vitis / chemistry*


  • Dietary Fats
  • Plant Extracts
  • Polyphenols
  • Proanthocyanidins
  • RNA, Ribosomal, 16S
  • Soybean Proteins
  • proanthocyanidin