Cross-species comparisons of host genetic associations with the microbiome

Abstract

Recent studies in human populations and mouse models reveal notable congruences in gut microbial taxa whose abundances are partly regulated by host genotype. Host genes associating with these taxa are related to diet sensing, metabolism, and immunity. These broad patterns are further validated in similar studies of nonmammalian microbiomes. The next generation of genome-wide association studies will expand the size of the data sets and refine the microbial phenotypes to fully capture these intriguing signatures of host-microbiome coevolution.

Figure 1. Environmental factors influence the gut microbiota and are controlled in model systems

Many factors affect the human gut microbiome (Left), adding noise to quantitative measures. Mice are an attractive model for studying host genetic-microbiome interactions as environmental variation is more tightly controlled (Right).

Figure 2. Lactase persistence and Bifidobacterium

LCT gene loci are linked to the relative abundances of Bifidobacteria. The direction of the effect indicates that lactase-persisters harbor fewer Bifidobacteria compared to lactase-non-persisters, which suggests the following hypothesis: (A) Lactase-persisters who ingest lactose (shown as milk) digest it directly, reducing lactose availability to Bifidobacterium and its relative levels. (B) Non-persisters consuming dairy products allow for lactose utilization by Bifidobacterium, thereby promoting its abundance. When no lactose is consumed (shown as espresso), Bifidobacterium is low regardless of lactase persistence status (C and D).