Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome.

TitleDietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome.
Publication TypeJournal Article
Year of Publication2015
AuthorsRoopchand, DE, Carmody, RN, Kuhn, P, Moskal, K, Rojas-Silva, P, Turnbaugh, PJ, Raskin, I
JournalDiabetes
Volume64
Issue8
Pagination2847-58
Date Published2015 Aug
ISSN1939-327X
KeywordsAnimals, Body Composition, Diet, High-Fat, Eating, Gastrointestinal Tract, Glucose Intolerance, Inflammation, Male, Metabolic Syndrome X, Mice, Microbiota, Polyphenols, Verrucomicrobia
Abstract

Dietary polyphenols protect against metabolic syndrome, despite limited absorption and digestion, raising questions about their mechanism of action. We hypothesized that one mechanism may involve the gut microbiota. To test this hypothesis, C57BL/6J mice were fed a high-fat diet (HFD) containing 1% Concord grape polyphenols (GP). Relative to vehicle controls, GP attenuated several effects of HFD feeding, including weight gain, adiposity, serum inflammatory markers (tumor necrosis factor [TNF]α, interleukin [IL]-6, and lipopolysaccharide), and glucose intolerance. GP lowered intestinal expression of inflammatory markers (TNFα, IL-6, inducible nitric oxide synthase) and a gene for glucose absorption (Glut2). GP increased intestinal expression of genes involved in barrier function (occludin) and limiting triglyceride storage (fasting-induced adipocyte factor). GP also increased intestinal gene expression of proglucagon, a precursor of proteins that promote insulin production and gut barrier integrity. 16S rRNA gene sequencing and quantitative PCR of cecal and fecal samples demonstrated that GP dramatically increased the growth of Akkermansia muciniphila and decreased the proportion of Firmicutes to Bacteroidetes, consistent with prior reports that similar changes in microbial community structure can protect from diet-induced obesity and metabolic disease. These data suggest that GP act in the intestine to modify gut microbial community structure, resulting in lower intestinal and systemic inflammation and improved metabolic outcomes. The gut microbiota may thus provide the missing link in the mechanism of action of poorly absorbed dietary polyphenols.

DOI10.2337/db14-1916
Alternate JournalDiabetes
PubMed ID25845659
PubMed Central IDPMC4512228
Grant ListF32 DK101154 / DK / NIDDK NIH HHS / United States
F32-DK-101154 / DK / NIDDK NIH HHS / United States
P50 AT002776 / AT / NCCIH NIH HHS / United States
P50-AT-002776-01 / AT / NCCIH NIH HHS / United States
R01 AT008618 / AT / NCCIH NIH HHS / United States
R01-AT-008618-01 / AT / NCCIH NIH HHS / United States