Regulation of Inflammation by Short Chain Fatty Acids

By M. Vinolo, H. Rodrigues, R. Nachbar, R. Curi. Nutrients, 2011

1,551 citations recorded by the source corpus.

The short chain fatty acids (SCFAs) acetate (C2), propionate (C3) and butyrate (C4) 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.

Subfields: Epidemiology, Nutrition and Dietetics, Physiology

View Paper: https://www.semanticscholar.org/paper/013d6d29017e4b3de5df05f540432ba3d3adc65e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Nutrition and Dietetics

1. P. Louis
2. H. Flint
3. S. Duncan
4. K. Scott
5. Pauline Young
6. A. Belenguer
7. Albert K. Groen
8. G. Holtrop

In Physiology

1. H. Flint
2. P. Louis
3. K. Verbeke
4. S. Duncan
5. K. Scott
6. E. Canfora
7. Ellen E. Blaak

Citations in the corpus

• Gut Bacteroides species in health and disease (2021, background): “Both acetate and propionate are potent anti-inflammatory mediators as they inhibit the release of pro-inflammatory cytokines from neutrophils and macrophages.(172) Cruz-Bravo et al.”
• Gut Microbiota and Immune System Interactions (2020, background): “By binding GPR109a on DCs and macrophages, the presence of butyrate leads to increased expression of IL-10 and decreased production of IL-6, resulting in increased Treg cell development while inhibiting the expansion of pro-inflammatory Th17 cells.”
• Phylogenetic distribution of three pathways for propionate production within the human gut microbiota (2014, background): “Propionate also has potential health-promoting effects that include anti-lipogenic, cholesterollowering, anti-inflammatory and anti-carcinogenic action (Hosseini et al., 2011; Vinolo et al., 2011).”
• Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism (2020, background): “In other studies, butyrate and propionate treatment can inhibit the secretion of TNFα and the activity of NF-κB and up-regulate the expression of anti-inflammatory factors IL-10 in LPS-activated mononuclear cells and neutrophils by HDAC inhibition [84,100,101].”
• Short chain fatty acids in human gut and metabolic health. (2020, positive): “Mechanistic insight into the direct effects of SCFA on inflammation comes mainly from in vitro and ex vivo experiments with isolated cells or tissues (Vinolo et al. , 2011).”
• The microbial metabolites, short chain fatty acids, regulate colonic Treg cell homeostasis (2013, background): “In SPF mice, SCFA are taken up by colonic epithelial cells but also diffuse through the epithelium into the lamina propria where they can mediate their effects directly (9, 14).”
• The role of short-chain fatty acids in immunity, inflammation and metabolism (2020, background): “…unfavorable to the host, such as excess amino acids when the supply of fermentable protein or cellulose exceeds supply (Cummings and Macfarlane 1991; Wall et al. 2009), which in turn will lead to reduced activity of the fermentation of the microbial community to produce SCFAs (Russell et al. 2011).”