Microbial Contribution to the Human Metabolome: Implications for Health and Disease

Abstract

The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Increasingly, studies are revealing that these chemicals impact host biology, either by acting on cells within the gastrointestinal tract or entering circulation and exerting their effects at distal sites within the body. Given the high level of functional diversity in the gut microbiome and the varied diets that we consume, the repertoire of microbiota-derived molecules within our bodies varies dramatically across individuals. Thus, the microbes in our gut and the metabolic end products they produce represent a phenotypic lever that we can potentially control to develop new therapeutics for personalized medicine. Here, we review current understanding of how microbes in the gastrointestinal tract contribute to the molecules within our gut and those that circulate within our bodies. We also highlight examples of how these molecules affect host physiology and discuss potential strategies for controlling their production to promote human health and to treat disease.

Keywords: human metabolome; human microbiome; metabolomics.

Figure 1

Metabolomics analysis of small molecules from the plasma of 100 healthy blood donors. Figure from unpublished data from the Stanford Microbiome-ChEM-H collaborative.

Figure 2

Chemical similarity map of metabolites detected in human feces. Nodes represent metabolites; blue lines represent chemical similarity; orange lines represent KEGG (Kyoto Encyclopedia of Genes and Genomes) reactions. Figure adapted from an image created with MetaMapp (http://metamapp.fiehnlab.ucdavis.edu).

Figure 3

Microbiota-dependent metabolites reported by metabolomics studies. Adapted with permission from Reference .

Figure 4

Classes of metabolites produced by gut bacteria. The gut microbiota produce short-chain fatty acids, branched-chain fatty acids, vitamins, lipids, amines, and aromatics, and modify bile acids and sterols.

Figure 5

Routes of absorption and elimination of microbial metabolites. Molecules are produced in the intestines and absorbed into portal circulation. Following metabolism in the liver, compounds are either secreted through the bile back into the intestine (enterohepatic circulation) or they enter the circulation, where they are eliminated in urine by the kidney.