Microbial communities in the human gut are formed at birth and shaped over time by a person’s diet, and other aspects of lifestyle and environment. Now scientists have confirmed that human genetic sequence polymorphisms also play a key role in shaping the gut microbiota.
Genetic variants influence food choices, immunity, and gut physiology, so it’s conceivable that they also have an impact on the microbiome. But previous research has been less than definitive. Most studies have relied on animal model experiments or small datasets from twin pairs. While some found signs of heritability, others did not (1, 2). Because many factors—particularly diet and environment—can have large influences on the microbiome, it’s difficult to attribute variations to host genetics rather than other influences, explains Julia Goodrich, first author on the new study. In an attempt to do so, the recent work leverages data from a large cohort of twin pairs.
Senior author Ruth Ley, a Cornell University microbiologist, and her colleagues first studied twin pairs from the TwinsUK database in 2014. Their analysis of 416 pairs suggested that monozygotic twins did indeed have more similar gut microbiota than dizygotic twins. Extending their analyses to nearly triple that sampling from the same database in the new study, published May 12 in Cell Host & Microbe, the researchers confirmed that finding. In a genome-wide association analysis, they compared host genetic variants to their microbiota to identify microbiotic “traits,” such as the presence of bacterial strains linked to blood pressure, that were likely influenced by host genetics.
The team gathered microbiotic data from 1126 pairs of twins, including 637 monozygotic pairs and 489 dizygotic twins. Although dietary and environmental factors might have made twins’ microbiota different from one another, the large sample size revealed statistically significant genetic effects, says Goodrich, a graduate student in Ley’s lab.
Many common groups of bacteria were heritable and stable over time, based on samples from a subset of the cohort more than two years after the first dataset. The researchers also found strong associations between host genetic variants and specific microbial groups. For example, an association between the host gene ALDH1L1 and SHA-98 bacteria suggested a link between blood pressure and the production of the gut chemical formate. Heritable bacteria were also strongly associated with the smell receptor OR6A2, which has been linked to the soapy taste of cilantro that some people experience. The data also validated previously identified associations, such as that between Bifidobacterium and genes for lactose metabolism.
Their study “suggests that even with all of these environmental factors that shape the gut microbiome, there are still genetic factors at play,” Goodrich says.
The genetic component is typically not particularly big, however. In the twins studied so far, it appears that the microbiome is less heritable than traits such as systolic blood pressure or serum vitamin D. In future work, the team aims to understand the mechanisms that drive some of the associations identified here using animal models.
The study is a “really important contribution to a challenging area of investigation,” says microbiologist David Relman of Stanford University, who was not involved in the study. “Only a limited amount of variation in the microbiome is explained by genetics here – but that’s just a result of the microbiome being a product of this blend of the host and environment.”
- Stewart, J.A., Chadwick, V.S., and Murray, A. (2005). Investigations into the inﬂuence of host genetics on the predominant eubacteria in the faecal microﬂora of children. J. Med. Microbiol. 54, 1239–1242.
- Turnbaugh, P.J., Hamady, M., Yatsunenko, T., Cantarel, B.L., Duncan, A., Ley, R.E., Sogin, M.L., Jones, W.J., Roe, B.A., Affourtit, J.P., et al. (2009). A core gut microbiome in obese and lean twins. Nature 457, 480–484.