Metabolic conversions of dietary carbohydrates by gut microbes

The human gastro-intestinal tract represents one of the body’s metabolically most active organs and is colonised by a myriad of microbes that vastly outnumber the human cells and that contribute significantly to nutrient-processing. Notably in the colon important metabolic conversions of dietary non-digestible substrates are realised by the colonic microbiota. This community of mostly anaerobic bacteria influences human gut-physiology and health by exerting a number of activities, including (a) fermentation of dietary compounds which escape digestion in the small intestine, and (b) the production of short-chain fatty acids, which are considered health-promoting. Although increasing insight has been obtained in the microbial diversity in the large intestine, there is very limited knowledge of (1) the metabolic function of these microbes, (2) the way the diet affects metabolic fluxes, and (3) how the produced metabolites affect the host. Moreover, it is known that metabolic distortion leads to significant intestinal health defects, such as colon cancer and inflammatory bowel disease, underpinning the importance of microbial metabolism. While the power of transcriptomics allows for the analysis of the expression of both microbial and host genes, functional insight is only possible by complementation of these transcriptomic experiments with a metabolomics approach. This contribution describes the use of a number of tools to study the metabolic conversions performed by gut microbes, with a focus on carbohydrate fermentation. Use is made of stable-isotope labelled substrates. The stable isotopes can be traced to metabolites that are produced from these substrates and to the microbial players involved in fermentation of these substrates.