The intestinal metabolome: an intersection between microbiota and host

Abstract

Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person's physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, the computational challenges in integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future data sets.

Keywords: Bacteria; Data Analysis; Metabolomics; Systems Biology.

Figure 1. Interactions Among Host, Microbiota, and Metabolites

In this simplified model, the gut microbiota metabolize substrate inputs from the host including diet and xenobiotics into metabolites that can enter the host’s bloodstream and affect the host peripherally. For example, therapeutic drugs can be inactivated, reducing their efficacy. Alternatively, drugs may converted to derivatives with non-target and possibly toxic effects. Changes in these input substrates, therefore, change the reservoir of available microbial substrates and alter the metabolomic profile of the gut, yielding variable effects on the host. The new host phenotype can, in turn, have a feedback effect on the microbial community.

Figure 2. Exploring the Interactions Between Metabolomics and the Microbiome

Both metabolomics and high-throughput sequencing produce a wealth of information. Visualizing the interactions between these highly multivariate datasets is important for elucidating relationships. In this example tripartite network, the large blue nodes represent samples, which are connected to red diamonds (metabolites) with red edges, and connected to black circles (OTUs) with black lines. The closer an OTU node or a metabolite node is to a sample node, the larger the relative abundance of that metabolite or that OTU in that sample. Therefore, OTUs and metabolites that are close together in the network tend to be found in the same samples (and this suggests, but does not conclusively prove, that the metabolite may be produced by that OTU). The tripartite network also demonstrates which metabolites and OTUs are shared by samples, and which metabolites and OTUs are unique to a given sample. As discussed in this review, methods are being developed to help separate out biologically important associations from amongst many statistically significant ones. Once identified, we can visualize how biologically important metabolites are controlled by the interaction between host and microbiome.