Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis

Cell Mol Gastroenterol Hepatol. 2021;11(2):525-550. doi: 10.1016/j.jcmgh.2020.09.008. Epub 2020 Sep 20.


Background & aims: The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis.

Methods: Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/- mice, respectively.

Results: Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding a HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10-/- mice and mice infected with C rodentium.

Conclusions: Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution, and metabolic function of resident enteric microbiota.

Keywords: Bile Acids; Colitis; Fructose; Microbiota.

Publication types

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

MeSH terms

  • Animals
  • Citrobacter rodentium / pathogenicity
  • Colitis / diagnosis
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / microbiology
  • Colon / immunology
  • Colon / microbiology
  • Colon / pathology
  • Dextran Sulfate / administration & dosage
  • Dextran Sulfate / toxicity
  • Dietary Sugars / adverse effects*
  • Disease Models, Animal
  • Feces / microbiology
  • Female
  • Fructose / adverse effects*
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Interleukin-10 / genetics
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Severity of Illness Index


  • Dietary Sugars
  • IL10 protein, mouse
  • Interleukin-10
  • Fructose
  • Dextran Sulfate