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

• Published in: International journal of molecular sciences Vol. 22; no. 12; p. 6453
• Main Authors: Sam, Qi Hui, Ling, Hua, Yew, Wen Shan, Tan, Zhaohong, Ravikumar, Sharada, Chang, Matthew Wook, Chai, Louis Yi Ann
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 16.06.2021; MDPI
• Subjects: Bacteria; Butyric acid; Carbon; cytokine; Cytokines; Diet; Fatty acids; Homeostasis; Hypoxia-inducible factor 1a; IL-1β; Immune system; immunity; Immunomodulation; Inflammation; Interferon regulatory factor 3; Interleukin 6; Intestinal microflora; Intestine; Ligands; medium chain fatty acids; Metabolism; Metabolites; microbiome; Molecular chains; Nutrition research; short chain fatty acids; TLR2 protein; TLR4 protein; TNF inhibitors; Toll-like receptors; TRAF6 protein; Trends; Tumor necrosis factor-α
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22126453

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.