The effect of microbial metabolites from colonic protein fermentation on bacteria-induced cytokine production in dendritic cells

Abstract

ScopeCompared to the well-defined immune-modulating effect of butyrate, the knowledge of other metabolites from colonic protein fermentation is limited. Methods and resultsThe effect of protein-derived metabolites (valerate, branched-chain fatty acids, ammonium, phenol, p-Cresol, indole, and H2S) on cytokine production in murine bone marrow-derived dendritic cells (BMDCs) stimulated with LPS, Lactobacillus acidophilus NCFM, or Staphylococcus aureus USA300 was investigated. The metabolites modulated the cytokine profile differently and depended on the specific microbial stimulus with short-chain fatty acids (SCFAs) exhibiting the strongest effects and no toxicity. After short-term treatment, SCFAs affected the cytokine profile similar to but weaker than butyrate, reflected by inhibition of IL-12p70 and IL-10 but enhanced IL-23 (LPS and S. aureus USA300) and IL-1{beta} production. Compared to valerate, butyrate exhibited a stronger and more prompt effect on cytokine gene expression without influencing reactive oxygen species (ROS) formation. Oppositely, long-term treatment with the two SCFAs resulted in similar anti-inflammatory effects, i.e. abrogation of LPS-induced IL-12 and enhancement of IL-10 and the expression of aryl hydrocarbon receptor (Ahr) and LPS-stimulated dual specificity phosphatase 1 (Dusp1). ConclusionOur data reveals immune-modulating effects of various protein fermentation metabolites, and valerate in specific holds activities resembling but not identical to butyrate.