Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Low Fiber Diet Minimize Colonic Short Chain Fatty Acids, Increase Severity and Prolongs Recovery in DSS Induced Colitis, Independent of Free Fatty Acid Receptor 2 and 3 Signaling

Jenna Elizabeth Hunt
ORCID logo ,
Charlotte Bayer Christiansen
,
Mohammad Yassin
,
Bolette Hartmann
ORCID logo ,
Stefan Offermanns
,
Lars Ove Dragsted
ORCID logo ,
Jens Juul Holst
ORCID logo ,
Hannelouise Kissow
* ORCID logo
Version 1 : Received: 31 May 2024 / Approved: 31 May 2024 / Online: 31 May 2024 (14:29:49 CEST)

A peer-reviewed article of this Preprint also exists.

Hunt, J.E.; Christiansen, C.B.; Yassin, M.; Hartmann, B.; Offermanns, S.; Dragsted, L.O.; Holst, J.J.; Kissow, H. The Severity of DSS-Induced Colitis Is Independent of the SCFA-FFAR2/3-GLP-1 Pathway Despite SCFAs Inducing GLP-1 Secretion via FFAR2/3. Metabolites 2024, 14, 395. Hunt, J.E.; Christiansen, C.B.; Yassin, M.; Hartmann, B.; Offermanns, S.; Dragsted, L.O.; Holst, J.J.; Kissow, H. The Severity of DSS-Induced Colitis Is Independent of the SCFA-FFAR2/3-GLP-1 Pathway Despite SCFAs Inducing GLP-1 Secretion via FFAR2/3. Metabolites 2024, 14, 395.

Abstract

Abstract: Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gut through the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and 3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lack of fiber affects the production of SCFAs and the vulnerability of the co-lon. Additionally, the involvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations in luminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs were applied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion of GLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of die-tary fiber significantly decreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, and butyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In the DSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severity was independent of FFAR2 and FFAR3 signaling.

Keywords

SCFA; colitis; mice; glp-1; fibre

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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