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

Abstract

AbstractScopeCompared 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 acidophilusNCFM, orStaphylococcus aureusUSA300 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 andS. aureusUSA300) and IL-1β 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.