The Divergent Immunomodulatory Effects of Short Chain Fatty Acids and Medium Chain Fatty Acids.

Qi Hui Sam,Louis Yi Ann Chai,Matthew Wook Chang,Sharada Ravikumar,Wen Shan Yew,Hua Ling,Zhaohong Tan

doi:10.3390/ijms22126453

Abstract

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1β, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet.

Highlights

The gut microbiome constitutes a complex pool of metabolites that play a pivotal role in the regulation of diverse bodily functions, from immunity to behavior [1]
Short chain fatty acids (SCFA) consist of free fatty acids with two to five carbons, the major SCFA produced by gut bacteria are acetic acid, propanoic acid, and butyric acid
We investigated the inflammatory pathways triggered by the SCFA and medium chain fatty acids (MCFA) by stimulating human peripheral blood mononuclear cells (PBMC) over an increasing concentration of SCFA or MCFA (2, 20 and 200 μM, derived from concentrations reported in the literature [14,15])

Summary

Introduction

The gut microbiome constitutes a complex pool of metabolites that play a pivotal role in the regulation of diverse bodily functions, from immunity to behavior [1]. Our ability to study the gut microbiome in recent years has reignited interest in studying diet–gut–immunity interaction These metabolites of lipid metabolism can influence the effector arms of the innate and acquired immune system, the details of which are not fully understood. Valeric acid ( known as pentanoic acid), isovaleric acid and 2-methylbutanoic acid, all consisting of five carbons, are produced by gut bacteria but in much smaller amounts, and their roles in the human body have been much less well-characterized [3]. All these SCFA are produced as by-products of fermentation of fiber and resistant starches by bacteria, mainly of the phyla Bacteroidetes and Firmicutes in the gut [4]

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