Short-chain fatty acids and their effect on dendritic cells

Short-chain fatty acids (SCFA) are metabolites produced from microbiota fermentation.  SCFAs have been subject to extensive investigation in attempts to delineate the pathways and mechanisms that underlie health outcomes from a species-host relationship.  Many have investigated the role of SCFAs in intestinal pathways or intestinal dysbiosis-driven disease (e.g. liver disease), but little is known as to how these metabolites interact with biological components of the immune system and blood stream.  Specifically, it is important to learn about this as some immune cells, such as dendritic cells (DC), patrol the blood stream to sense and respond to bacterial metabolites and present these pathogens to other immune cells in the lymph nodes.  To investigate further, a European conglomerate of researchers examined the interaction between SCFAs and DCs at the molecular level.

PCR was first performed on human-derived DCs to characterize protein expression patterns of SCFA receptors on these cells, as SCFAs are postulated to be ligands for G-coupled protein receptors (supported by the PCR).  Next, still using human-derived DCs the researchers determined that individual SCFAs were shown to have different effects, more so on mature DCs.  Butyrate and propionate in particular strongly modulated gene expression in both immature and mature human DCs.  The researchers next conducted an ingenuity pathway analysis based on differential gene expression which determined that propionate and butyrate modulate leukocyte (white blood cell) trafficking.  On top of this, SCFA significantly tempered release of an array of pro-inflammatory cytokines.  Lastly, butyrate and propionate were shown to inhibit the expression of lipopolysaccharide-induced cytokines to support a strong anti-inflammatory effect.

Together, these results suggest that metabolites derived from microbiota fermentation and metabolism and differentially modulate inflammatory response by way of dendritic cell interaction.  These findings illustrate another key component to the host-species relationship, and provide more evidence as to the scale and important of a healthy synergistic relationship between host and microbiome as the interactions are involved in disease-prone pathways that require careful molecular regulation (e.g. inflammation and immunity).  This in vitro study was a good first step in this investigation.  

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