Are Short Chain Fatty Acids in Gut Microbiota Defensive Players for Inflammation and Atherosclerosis?

Overview

Journal J Atheroscler Thromb

Date 2017 May 30

PMID 28552897

Citations 211

Authors

Hideo Ohira

Wao Tsutsui

Yoshio Fujioka

Affiliations

Soon will be listed here.

Abstract

Intestinal flora (microbiota) have recently attracted attention among lipid and carbohydrate metabolism researchers. Microbiota metabolize resistant starches and dietary fibers through fermentation and decomposition, and provide short chain fatty acids (SCFAs) to the host. The major SCFAs acetates, propionate and butyrate, have different production ratios and physiological activities. Several receptors for SCFAs have been identified as the G-protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3), GPR43/FFAR2, GPR109A, and olfactory receptor 78, which are present in intestinal epithelial cells, immune cells, and adipocytes, despite their expression levels differing between tissues and cell types. Many studies have indicated that SCFAs exhibit a wide range of functions from immune regulation to metabolism in a variety of tissues and organs, and therefore have both a direct and indirect influence on our bodies. This review will focus on SCFAs, especially butyrate, and their effects on various inflammatory mechanisms including atherosclerosis. In the future, SCFAs may provide new insights into understanding the pathophysiology of chronic inflammation, metabolic disorders, and atherosclerosis, and we can expect the development of novel therapeutic strategies for these diseases.

Citing Articles

Oral intake of Hibiscus sabdariffa L. increased c-Myc and caspase-3 gene expression and altered microbial population in colon of BALB/c mice induced to preneoplastic lesions.

Ladeira Bernardes A, Albuquerque Pereira M, Xisto Campos I, Avila L, Dos Santos Cruz B, Duarte Villas Mishima M Eur J Nutr. 2025; 64(3):109.

PMID: 40042671 DOI: 10.1007/s00394-025-03622-z.

Microbial effects of cold-pressed Sacha inchi oil supplementation in rats.

Samrit T, Osotprasit S, Chaiwichien A, Suksomboon P, Chansap S, Suthisintong T PLoS One. 2025; 20(2):e0319066.

PMID: 39977445 PMC: 11841868. DOI: 10.1371/journal.pone.0319066.

Exploring the Role of Salt Supplementation on Milk Composition, Fatty Acids, and Insulin Response in Lactating Camels.

Aljumaah R, Salama A, Abdelrahman M, Ayadi M, Caja G, Alshaikh M Vet Sci. 2025; 12(1.

PMID: 39852897 PMC: 11768427. DOI: 10.3390/vetsci12010022.

Predicting metabolite response to dietary intervention using deep learning.

Wang T, Holscher H, Maslov S, Hu F, Weiss S, Liu Y Nat Commun. 2025; 16(1):815.

PMID: 39827177 PMC: 11742956. DOI: 10.1038/s41467-025-56165-6.

Gut microbiota in post-acute COVID-19 syndrome: not the end of the story.

An Y, He L, Xu X, Piao M, Wang B, Liu T Front Microbiol. 2025; 15():1500890.

PMID: 39777148 PMC: 11703812. DOI: 10.3389/fmicb.2024.1500890.

References

Ryan P, London L, Bjorndahl T, Mandal R, Murphy K, Fitzgerald G . Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E mice. Microbiome. 2017; 5(1):30. PMC: 5346842. DOI: 10.1186/s40168-017-0246-x. View

Taggart A, Kero J, Gan X, Cai T, Cheng K, Ippolito M . (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005; 280(29):26649-52. DOI: 10.1074/jbc.C500213200. View

Hylla S, Gostner A, Dusel G, Anger H, Bartram H, Christl S . Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. Am J Clin Nutr. 1998; 67(1):136-42. DOI: 10.1093/ajcn/67.1.136. View

Suganami T, Nishida J, Ogawa Y . A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol. 2005; 25(10):2062-8. DOI: 10.1161/01.ATV.0000183883.72263.13. View

Louis P, Hold G, Flint H . The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014; 12(10):661-72. DOI: 10.1038/nrmicro3344. View

Macfarlane G, Macfarlane S . Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 2012; 95(1):50-60. DOI: 10.5740/jaoacint.sge_macfarlane. View

Vinolo M, Ferguson G, Kulkarni S, Damoulakis G, Anderson K, Bohlooly-Y M . SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS One. 2011; 6(6):e21205. PMC: 3115979. DOI: 10.1371/journal.pone.0021205. View

Fleischer J, Bumbalo R, Bautze V, Strotmann J, Breer H . Expression of odorant receptor Olfr78 in enteroendocrine cells of the colon. Cell Tissue Res. 2015; 361(3):697-710. DOI: 10.1007/s00441-015-2165-0. View

Pluznick J . A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014; 5(2):202-7. PMC: 4063845. DOI: 10.4161/gmic.27492. View

10.

Chambers E, Viardot A, Psichas A, Morrison D, Murphy K, Zac-Varghese S . Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2014; 64(11):1744-54. PMC: 4680171. DOI: 10.1136/gutjnl-2014-307913. View

11.

McOrist A, Miller R, Bird A, Keogh J, Noakes M, Topping D . Fecal butyrate levels vary widely among individuals but are usually increased by a diet high in resistant starch. J Nutr. 2011; 141(5):883-9. DOI: 10.3945/jn.110.128504. View

12.

Ohira H, Fujioka Y, Katagiri C, Yano M, Mamoto R, Aoyama M . Butyrate enhancement of inteleukin-1β production via activation of oxidative stress pathways in lipopolysaccharide-stimulated THP-1 cells. J Clin Biochem Nutr. 2012; 50(1):59-66. PMC: 3246184. DOI: 10.3164/jcbn.11-22. View

13.

Ge H, Li X, Weiszmann J, Wang P, Baribault H, Chen J . Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008; 149(9):4519-26. DOI: 10.1210/en.2008-0059. View

14.

Mirmonsef P, Zariffard M, Gilbert D, Makinde H, Landay A, Spear G . Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands. Am J Reprod Immunol. 2011; 67(5):391-400. PMC: 3288536. DOI: 10.1111/j.1600-0897.2011.01089.x. View

15.

Wang X, He G, Peng Y, Zhong W, Wang Y, Zhang B . Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway. Sci Rep. 2015; 5:12676. PMC: 4522654. DOI: 10.1038/srep12676. View

16.

Freeland K, Wolever T . Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2009; 103(3):460-6. DOI: 10.1017/S0007114509991863. View

17.

Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I . Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015; 7(4):2839-49. PMC: 4425176. DOI: 10.3390/nu7042839. View

18.

Ohira H, Tsutsui W, Mamoto R, Yamaguchi S, Nishida M, Ito M . Butyrate attenuates lipolysis in adipocytes co-cultured with macrophages through non-prostaglandin E2-mediated and prostaglandin E2-mediated pathways. Lipids Health Dis. 2016; 15(1):213. PMC: 5148837. DOI: 10.1186/s12944-016-0387-0. View

19.

Al-Lahham S, Roelofsen H, Priebe M, Weening D, Dijkstra M, Hoek A . Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest. 2010; 40(5):401-7. DOI: 10.1111/j.1365-2362.2010.02278.x. View

20.

Lumeng C, Bodzin J, Saltiel A . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117(1):175-84. PMC: 1716210. DOI: 10.1172/JCI29881. View