Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet

Food Funct. 2019 Dec 11;10(12):8273-8285. doi: 10.1039/c9fo02077b.

Abstract

Recent studies have found that a high-fat diet (HFD) causes gut microbiota imbalance and colon tissue damage, resulting in increased intestinal permeability, which is one of the main reasons for the existence of constantly circulating low-grade inflammatory cytokines. Pomegranate extracts have been shown to protect from HFD-induced metabolic inflammation (e.g., colitis) and to promote the growth of beneficial bacteria in in vitro stool cultures. However, whether the beneficial effects of pomegranate extracts on the HFD-induced metabolic inflammation are achieved by acting on intestinal tissues has not yet been studied. In our present study, we found that pomegranate peel polyphenols (PPPs) alleviated HFD-induced obesity, elevated circulating pro-inflammatory cytokines, colonic tissue damage, and depressed colonic tight junction protein expression level in rats. Moreover, PPPs normalized the HFD-induced gut microbiota imbalance by increasing the abundance of beneficial bacteria in the colon. Furthermore, we also found that PPPs, punicalagin, and urolithin A (the main microbiota metabolites of pomegranate ellagitannins) all increased the LPS-induced decreased tight junction protein expression level and reversed the LPS-induced inflammatory response in Caco-2 cells. Urolithin A exhibited the best effects among the three pomegranate components. Our results suggested that the protective effects of PPPs in HFD-induced metabolic inflammation can be due to the recovery of colonic tissue damage and the regulation of gut microbiota and that urolithin A is the major component that contributes to the in vivo effects of PPPs.

MeSH terms

  • Animals
  • Colitis / drug therapy*
  • Colitis / etiology
  • Colitis / immunology
  • Colitis / microbiology
  • Colon / immunology
  • Colon / microbiology
  • Coumarins / administration & dosage
  • Coumarins / analysis
  • Diet, High-Fat / adverse effects
  • Fruit / chemistry
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Hydrolyzable Tannins / administration & dosage
  • Hydrolyzable Tannins / analysis
  • Inflammation
  • Male
  • Plant Extracts / administration & dosage*
  • Plant Extracts / analysis
  • Polyphenols / administration & dosage*
  • Polyphenols / analysis
  • Pomegranate / chemistry*
  • Rats
  • Waste Products / analysis

Substances

  • Coumarins
  • Hydrolyzable Tannins
  • Plant Extracts
  • Polyphenols
  • Waste Products
  • 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
  • punicalagin