A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice

Michael Laffin,Karen L Madsen,Aiden Zalasky,Naomi Hotte,Ambika Agrawal,Robert Fedorak,Ammar Keshteli,Heekuk Park,Amanpreet Gill

doi:10.1038/s41598-019-48749-2

Michael Laffin, Karen L Madsen + Show 7 more

Open Access

https://doi.org/10.1038/s41598-019-48749-2

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Journal: Scientific Reports	Publication Date: Aug 23, 2019
Citations: 118	License type: open-access

Affiliation: University of Alberta

Abstract

Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.

Highlights

Inflammatory bowel disease (IBD), and its two subtypes Crohn’s disease and ulcerative colitis are multifactorial in nature, developing due to a complex interplay between genetic, environmental, microbial, and immunologic factors[1]
Mice on a high sugar diet (HS; n = 5) for two days had no changes in weight, caloric consumption, or general activity level compared with mice which remained on chow diet
In this study we demonstrate that a two-day exposure to a high-sugar diet rapidly alters gut microbial composition, depletes short chain fatty acids and increases susceptibility to chemically induced colitis

Summary

Introduction

Inflammatory bowel disease (IBD), and its two subtypes Crohn’s disease and ulcerative colitis are multifactorial in nature, developing due to a complex interplay between genetic, environmental, microbial, and immunologic factors[1]. Firmicutes and/or Bacteroides and an increase in relative abundance of Proteobacteria have been described in numerous publications[21,22] Whether these alterations in gut microbiota are causal or occur due to the presence of inflammation in the intestine remains to be conclusively demonstrated[23]. We aimed to assess the impact of a short-term dietary exposure to high sugar on colitis susceptibility in order to examine how daily fluctuations in diet may trigger disease flares in susceptible patients. Given the apparent relationship between a high-sugar diet and colitis we hypothesized that a diet high in refined sugar would elicit alterations in gut microbial metabolism and increase disease susceptibility

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