Human genetic variation and the gut microbiome in disease

Key Points Host genetics shape the composition of the gut microbiome in concert with environmental factors such as diet and lifestyle. Certain host genetic variants predispose an individual towards microbiome dysbiosis, which is an important factor in diseases of metabolism and immunity. A subset of species in the gut microbiome are heritable, especially representatives from the phyla Firmicutes and Verrucomicrobia. Variants in single genes (for example, LCT , NOD2 and FUT2 ) affect the composition of the gut microbiome. Microbiome genome-wide association studies hold promise for the identification of additional host genetic variants that affect disease progression by perturbing the composition of the microbiome. Recent microbiome genome-wide association studies have identified numerous associations between human genetic variants and the gut microbiome. Here, the authors review how genetic variation in the host can alter the composition of the gut microbiome towards a disease state, with a focus on disorders of immunity and metabolism. Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.