Short chain fatty acids (SCFAs)mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases

Daniela Parada Venegas, Marjorie K. De La Fuente, Glauben Landskron, María Julieta González, Rodrigo Quera, Gerard Dijkstra, Hermie J.M. Harmsen, Klaas Nico Faber, Marcela A. Hermoso

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427 Scopus citations

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

Original languageEnglish
Article number277
JournalFrontiers in Immunology
Volume10
Issue numberMAR
DOIs
StatePublished - 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Fund for Scientific and Technological Development No. 1170648 (MH); National Commission for Scientific and Technological Research Scholarship No.21150517 (DPV). The figures were produced using Servier Medical Art from https://smart.servier.com/. We would like to thank David Cox and Octavio Orellana for their editing contribution.

Funding Information:
This work was supported by National Fund for Scientific and Technological Development No. 1170648 and National Commission for Scientific and Technological Research REDES No. 180134 (PCI) (MH); National Commission for Scientific and Technological Research Scholarship No. 21150517 (DPV). The figures were produced using Servier Medical Art from https:// smart.servier.com/. We would like to thank David Cox and Octavio Orellana for their editing contribution.

Publisher Copyright:
© 2019 Parada Venegas, De la Fuente, Landskron, González, Quera, Dijkstra, Harmsen, Faber and Hermoso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords

  • Dysbiosis
  • IBD
  • IECs
  • Immune cells
  • Intestinal mucosa
  • SCFAs

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