Role of host genetics on gut microbiome is near-universal, but environmentally-dependent

"In humans, research has shown that family members share a significant portion of microbes in their gut, but it's hard to answer if our microbiome is shaped more by nature, such as those we inherit from our family, or nurture, such as the similar diets, environments and behaviors families share," said lead author Laura Grieneisen, a postdoctoral fellow in the College of Biological Sciences. "Many human diseases and other markers of health have a genetic component. The number and types of bacteria in the gut are no different. By understanding the heritability of the gut microbiome will help us better link genes, the gut and health."

To examine consistent data, researchers turned to more than 16,000 microbiome samples collected from 585 wild baboons over the course of 14 years. The size and generational scope of this microbiome data -- crucial for understanding how the microbiome is affected by genetics (i.e. microbiome heritability) -- has not yet been collected in humans.

In the research, published in the journal Science, the team tested how host traits (e.g., age, sex), behaviors (e.g., social group membership, grooming), diet, pedigree relatedness, and environmental characteristics (e.g., season, year) predicted 1,034 gut microbiome traits.

Researchers found that:

• while prior research in humans indicated that heritable gut microbiome taxa (i.e., species, family and class of an organism) were uncommon, 95% of microbial taxa were heritable in the wild baboon population;
• heritability estimates are strongly and positively correlated between humans and baboons, suggesting that traits with low heritability in baboons may also be heritable -- but have gone undetected -- in humans;
• microbiome heritability is dynamic and context-dependent, such that heritability is greater in the dry season, with low diet diversity, and in older hosts.

"Our results qualitatively change the field's perspective on the determinants of microbiome composition," said co-author Ran Blekhman, an associate professor in the College of Biological Sciences. "From one in which the host genotype plays no role in the majority of microbiome taxa to one in which the host genotype nearly always plays a role. As a result, microbiome traits might evolve via natural selection on the host."

Researchers state that this opens the door to identifying individual microbes that are particularly shaped by host genetics.

"As a result, if there are microbes that are heritable and linked to health outcomes, it would allow us to better understand the genetic basis of these outcomes," said Grieneisen. "Most of the microbiome may be visible to natural selection on the host genome."

The researchers add that their results are consistent with past work: although the role of a host's genotype is universal, their environment and behaviors are still much more important than genetics in shaping microbiome composition. The team will continue to work with the wild baboon dataset to pursue questions about the drivers and physiological consequences of long-term changes in the microbiome.

This research was supported by funding from the National Institutes of Health, the University of Minnesota Grand Challenges Biology Postdoctoral

Fellowship, the Duke University Population Research Institute and the University of Notre Dame's Eck Institute for Global Health.