The effect of short-chain fatty acids on human monocyte-derived dendritic cells

Abstract

The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions.

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo

“…Similar disparities have been observed with other SCFAs2940454654. BMDCs were more resistant to propionate than BMDMs, human monocytes and whole blood.…”

“…Considering that SCFAs carry anti-inflammatory activity and that HDACi were shown to increase susceptibility to infections in preclinical models and in patients enrolled in oncologic clinical studies293435363738, an important question is whether SCFA-mediated therapies are safe. Here we focused on propionate as a representative SCFA reported to modulate adaptive immune responses in vivo 3940414243. We analyzed the response of macrophages, dendritic cells (DCs), splenocytes and whole blood to microbial compounds.…”

ZEB1‐regulated inflammatory phenotype in breast cancer cells

“…2F and G). Notably, the amounts of proteins secreted by MDA‐231‐D cells were comparable to the levels secreted by inflammatory cells, suggesting that IL‐6 and IL‐8 were produced at functional levels (Nastasi et al ., 2015; Pazmandi et al ., 2012). …”

Gut microbiota and hematopoietic stem cell transplantation: where do we stand?

“…Non-GvHD subjects have a higher abundance of members of the Bacteroidetes phylum, known to produce SCFA from dietary fiber, 55 influencing both the magnitude and the quality of the immune response. 60 SCFA are end products of microbial fermentation of complex plant polysaccharides that cannot be digested by humans alone, because our genomes do not encode an adequate repertoire of glycoside hydrolases. 61 SCFA are one of the clearest examples of how diet and nutrient processing by the microbiota combine to shape immune responses.…”