The Relationship Between the Human Genome and Microbiome Comes into View

Abstract

The body's microbiome, composed of microbial cells that number in the trillions, is involved in human health and disease in ways that are just starting to emerge. The microbiome is assembled at birth, develops with its host, and is greatly influenced by environmental factors such as diet and other exposures. Recently, a role for human genetic variation has emerged as also influential in accounting for interpersonal differences in microbiomes. Thus, human genes may influence health directly or by promoting a beneficial microbiome. Studies of the heritability of gut microbiotas reveal a subset of microbes whose abundances are partly genetically determined by the host. However, the use of genome-wide association studies (GWASs) to identify human genetic variants associated with microbiome phenotypes has proven challenging. Studies to date are small by GWAS standards, and cross-study comparisons are hampered by differences in analytical approaches. Nevertheless, associations between microbes or microbial genes and human genes have emerged that are consistent between human populations. Most notably, higher levels of beneficial gut bacteria called Bifidobacteria are associated with the human lactase nonpersister genotype, which typically confers lactose intolerance, in several different human populations. It is time for the microbiome to be incorporated into studies that quantify interactions among genotype, environment, and the microbiome in order to predict human disease susceptibility.

Keywords: genome-wide association studies; heritability; human studies; microbiome; microbiota composition.

Figure 1. Heritability and genome-wide association studies of the human gut microbiome

The top panel shows a world map indicating the locations and relative sample size of the currently published human gut microbiome heritability and GWA studies. Each colored circle represents a single study and the size of the circle indicates the study’s sample size. The bottom panel is a comparison of taxon heritability across studies. Only taxa found to have nominally significant heritability estimates (P < 0.05 or in the case of Davenport et al. ‘chip heritability’ estimates with a standard error not overlapping 0) in at least two of the four heritability studies are shown in the bar chart (bars are colored by study).

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