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Monday, April 10, 2017

Inflammation regulation by short chain fatty acids

Abstract (as presented by the authors of the scientific work):

"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."

Covered topics (the letter size corresponds to the frequency of mentioning in the text):

Conclusions (as presented by the authors of the scientific work):

"SCFAs present multiple effects in different cells involved in the inflammatory and immune responses. These fatty acids not only affect the function of leukocytes (e.g., production of inflammatory mediators and ability of leukocytes to migrate) but can also induce apoptosis in lymphocytes [96,97], macrophages [98] and neutrophils [99]. The latter effect may be relevant for the outcome of the inflammatory process and the immune response to bacteria that produce these fatty acids.

In general, SCFAs, such as propionate and butyrate, inhibit stimuli-induced expression of adhesion molecules, chemokine production and consequently suppress monocyte/macrophage and neutrophil recruitment, suggesting an anti-inflammatory action. However, there is also evidence in favor of a pro-inflammatory action of SCFAs in some conditions [20,100]. This discrepancy may be in part explained by the ability of SCFAs to induce neutrophil migration. In sites of anaerobic bacteria infection or after loss of intestinal epithelial integrity, high concentrations of SCFAs may lead to neutrophil accumulation and amplification of the inflammatory process. Another possible explanation is the fact that these fatty acids may present divergent effects depending on the cell type (e.g., anti- and pro-inflammatory effects of SCFAs on macrophage and microglial cells have been demonstrated [52,97,101]). Therefore, although SCFAs modulate the function of immune cells, more studies are necessary in order to understand the precise role of SCFAs on the interaction between bacteria and host immune cells in vivo, particularly in the GI tract and in sites of anaerobic infections including the skin, oral cavity and respiratory tract."

Full-text access of the referenced scientific work:

Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by
short chain fatty acids. Nutrients. 2011 Oct;3(10):858-76. doi:
10.3390/nu3100858. Epub 2011 Oct 14. Review. PubMed PMID: 22254083; PubMed
Central PMCID: PMC3257741.


Prof. Atanas G. Atanasov (Dr. habil., PhD)

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