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

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...

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Autores principales:	Michael Laffin, Robert Fedorak, Aiden Zalasky, Heekuk Park, Amanpreet Gill, Ambika Agrawal, Ammar Keshteli, Naomi Hotte, Karen L. Madsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9320edf6327486489fc4b53191223e5
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spelling	oai:doaj.org-article:b9320edf6327486489fc4b53191223e52021-12-02T15:10:02ZA high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice10.1038/s41598-019-48749-22045-2322https://doaj.org/article/b9320edf6327486489fc4b53191223e52019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48749-2https://doaj.org/toc/2045-2322Abstract 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.Michael LaffinRobert FedorakAiden ZalaskyHeekuk ParkAmanpreet GillAmbika AgrawalAmmar KeshteliNaomi HotteKaren L. MadsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael Laffin Robert Fedorak Aiden Zalasky Heekuk Park Amanpreet Gill Ambika Agrawal Ammar Keshteli Naomi Hotte Karen L. Madsen A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
description	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.
format	article
author	Michael Laffin Robert Fedorak Aiden Zalasky Heekuk Park Amanpreet Gill Ambika Agrawal Ammar Keshteli Naomi Hotte Karen L. Madsen
author_facet	Michael Laffin Robert Fedorak Aiden Zalasky Heekuk Park Amanpreet Gill Ambika Agrawal Ammar Keshteli Naomi Hotte Karen L. Madsen
author_sort	Michael Laffin
title	A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
title_short	A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
title_full	A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
title_fullStr	A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
title_full_unstemmed	A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
title_sort	high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/b9320edf6327486489fc4b53191223e5
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A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice

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