Host Genetics and Gut Microbiome: Challenges and Perspectives

The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health including metabolism and immunity. While environmental factors such as diet and medications have been shown to influence the microbiome composition, the role of host genetics has only recently emerged in human studies and animal models. In this review, we summarize the current state of microbiome research with an emphasis on the effect of host genetics on the gut microbiome composition. We focus particularly on genetic determinants of the host immune system that help shape the gut microbiome and discuss avenues for future research. A proportion of gut bacteria are heritable. The impact of host genetics on the gut microbiome in humans is being revealed through genome-wide association studies. The effect size of host genetics on the microbiome appears to be modest. Several associations are found between the microbiome and genes associated with diet, innate immunity, vitamin D receptors, and metabolism. A consistent genetic signal comes from pattern recognition receptor molecules, particularly C-type lectins.