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Review
. 2011 Oct;3(10):858-76.
doi: 10.3390/nu3100858. Epub 2011 Oct 14.

Regulation of inflammation by short chain fatty acids

Marco A R Vinolo  1 , Hosana G Rodrigues, Renato T Nachbar, Rui Curi
Affiliations
Review

Regulation of inflammation by short chain fatty acids

Marco A R Vinolo et al. Nutrients. 2011 Oct.

Abstract

The short chain fatty acids (SCFAs) acetate (C(2)), propionate (C(3)) and butyrate (C(4)) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted.

Keywords: short chain fatty acids; acetate; butyrate; inflammation; leukocytes; neutrophils; propionate.

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Figures

Figure 1
Figure 1
Schematic representation of the interaction between gut microbiota and host tissues. Soluble factors (e.g., LPS, flagellin, ATP and short chain fatty acids (SCFAs)) released by gut microbiota modulate host tissues such as pancreas, skeletal muscle (SM), adipose tissue (AT), leukocytes, liver and blood vessels function and may play a role in the development of several diseases including cancer, inflammation and diabetes.
Figure 2
Figure 2
Schematic overview of the signaling pathways activated downstream of GPR43 receptors and representation of the effects of SCFAs through inhibition of histone deacetylase (HDAC) activity (B). GPR43 couples to Gi and Gq proteins, which interact with several proteins including adenylate cyclase, small G proteins (e.g., Rac and Rho), mitogen-activated protein kinases (MAPK), phospholipase C (PLC) and A2 (PLA2), ion channels and transcription factors (A). SCFAs may also act on cells through inhibition of HDAC (B). This class of enzymes, together with histone acetyltransferase (HAT), controls the acetylation state of histones and non-histone proteins and, consequently, modulates the transcription of several genes.
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