Microbial metabolites produced by the colonic microbiota as drivers for immunomodulation in the host

The colonic microbiota ferments dietary substrates that are not digested in the upper GI tract, such as complex carbohydrates. Fermentation of these leads to the production of short chain fatty acids (SCFA), which have been shown to have several beneficial effects on the host, including functioning as immune signaling molecules. For instance, butyrate has been shown to reduce inflammation in inflammatory bowel disease, possibly through its histone deacetylase inhibitory activity. Propionate has effects on cells in the adipose tissue. The SCFA are hypothesized to signal through G‐protein coupled receptors. However, we have shown that additional pathways must be active. Several tools were combined to study SCFA production by the colonic microbiota, including a sophisticated, in vitro model of the colon including a complex microbiota, 13 C stable isotope technology, and reporter cell assays. The microbiota used originated from several different volunteers, e.g., different ages, healthy or diseased. We have shown that different microbiotas lead to production of different ratios of SCFA, and thus may be portrayed to have different health effects in these individuals. Using specific prebiotics, the activity of the microbiota can be directed towards production of certain SCFA, and through this the immunomodulation in the host can be influenced.