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The gut microbiome—an emerging complex trait

Nature Genetics volume 48, pages 1301–1302 (2016)Cite this article

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As the first series of genetic analyses of gut microbiome composition in humans is now emerging, the results should be met with enthusiasm, but also with caution. Findings from the initial offerings demonstrate how population-scale approaches can provide deeper insights into host–microbiome interactions while at the same time illustrating that our understanding of the architecture of highly complex microbiome 'traits' is still rudimentary.

The species composition of the mammalian gut microbiome is complex and highly individualized, but features such as abundance of individual taxa behave as polygenic traits when studied across populations. Initial studies in mice, where some environmental factors can be carefully controlled, found significant associations between variation at individual loci and abundance of individual taxa, showing that discovery approaches using quantitative genetics could provide hypotheses for understanding the mechanics of host–microbe interactions1,2,3,4,5. With approaches powered by high-density genotyping and sophisticated statistical analyses, many in the field are now moving from genetic analysis in model organisms to studies in humans. Genetic analysis of human microbiome traits in populations of twins and individuals from the Human Microbiome Project showed that associations with microbiome features could be detected across multiple body sites and that some of the most heritable taxa seem to have roles in structuring the microbiome6,7. Subsequent analysis in a larger population also identified highly heritable taxa, but genome-wide association analysis found only suggestive associations, even for the most highly heritable organisms8.

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Figure 1: The spectrum of quantitative features of the microbiome giving rise to significant trait associations.

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  1. Department of Food Science and Technology, Andrew K. Benson is at the Nebraska Food for Health Center, University of Nebraska, Lincoln, Nebraska, USA.,

    Andrew K Benson

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Benson, A. The gut microbiome—an emerging complex trait. Nat Genet 48, 1301–1302 (2016). https://doi.org/10.1038/ng.3707

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