A host’s genetics shape its gut microbiome

Cattle grazing at sunrise in the morning fog
Cattle grazing at sunrise in the morning fog. UF/IFAS Photo: Thomas Wright.

New research by EPI investigator KC Jeong looks at how a host’s genetic background strongly influences the composition and development of its gut microbiota.

Researchers know that many different factors affect the development and composition of a mammal’s gut microbiota, but the role of a host’s genetics remain unclear. New research from UF’s Emerging Pathogens Institute offers steps toward clarity by demonstrating that a host’s genetic background exerts a strong influence on how its gut microbiome develops.

EPI investigator KC Jeong, Ph.D., worked with colleagues in IFAS’s animal sciences department to analyze the early development of gut microbe populations in beef cows that were bred on a graduated spectrum from pure Angus to pure Brahman. Their work recently published in the Nature Publishing Group’s ISME Journal. (Jeong shares a joint appointment between the EPI and IFAS’s animal science department.)

“It’s possible this line of inquiry could lead to the establishment of new targets that maintain homeostasis in the gastrointestinal tract, which could possibly prevent illness or disease,” Jeong says. 

The researchers used Brahman and Angus breeds, and their associated characteristics, as a proxy for model animals with varying genetic profiles. Brahman cattle are prized for tolerating extreme heat and their resistance to parasites, while Angus are known as hardy cattle that produce superior marbled meat. They then controlled for the influence of environmental factors by raising the calves uniformly: they were fed the same diet, drank the same water, and grazed on the same pastures.

“Previously, due to discrepancies in population variation, genetic distance, age, and environmental conditions, effects of host genetics haven’t been measured correctly,” Jeong says. “We believe we have corrected for some of these variables and were very pleased to see such a strong signal of genetic influence in our study.”

Only pre-weaning calves up to the age of three months were studied because at this stage, the rumen is not entirely developed, and the hindgut is critical for harvesting energy from food. This is also when the animals’ immunity begins to develop, and its gut microbiota tend to be more diverse in comparison to later life stages.

The researchers hypothesized that each breed would harbor distinct gut microbiota due to genetic influences connected to breeding heritage; and that animals would show a proportional blending of the gut microbiome profiles associated with the proportion of breed or breeds in their own composition.

Calves were assigned to six breed groups that change on a graduated spectrum from 100 percent Angus to 100 percent Brahman:

They found that pre-weaning calves housed gut microbiota which was strongly affected by the host’s breed or genetics. Further, paternal genomes had an outsized effect on the young calves’ gut microbiome development in comparison to the maternal contribution. No other studies, to the authors’ knowledge, have documented this particular finding.

The researcher’s initial hunch proved true: the composition of bacteria identified as core to the gut microbe population of these calves tended to change linearly with the calf population’s own gradual, proportional change of breed background.

Calves with a higher proportion of Angus background were found to have comparatively more abundance of mucin-degrading bacteria in their GI tracts. Mucin is critical for cows to maintain a healthy mucosal lining in their intestines, and mucin-degrading bacteria disrupt it to obtain carbon and nitrogen for their own use. The resulting breakdown of the intestinal barrier leaves the calves susceptible to GI pathogens.  The proportion of mucin-degrading bacteria increased as a calf’s own proportion of Angus background increased.

In a similar vein, calves with a higher proportion of Brahman background were found to have elevated levels of fiber-digesting bacteria, which is helpful for maximizing nutrition gleaned from forage. They also had elevated levels of butyrate-producing bacteria, which provide anti-inflammatory benefits.

Attesting to the influence of genes, the proportion of butyrate-producing bacteria increased as a calf’s own proportion of Brahman background increased.

This finding is interesting because Brahman are known to better utilize low-quality feeds, particularly ones with low concentrations of protein and soluble carbohydrates. It’s likely that the nutritional benefits to the calves of specific gut bacteria are so strong that selective forces favor particular microbes; the authors posit this happens either through direct contact or via genetic influence mediated by the parental genome. Other work also indicates that some bacterial taxa are inherited and a host’s genetics may play a key role in moderating bacterial specificity.

“Gut bugs are all the rage,” Jeong says. “Learning to manipulate the types of bacteria populating the gastro-intestinal tracts of food animals offers a tantalizing tool to mitigate food-borne illnesses. Knowing this connection will give us better insights to breed animals for targeted benefits.” Jeong says.

Food animals such as beef cattle are reservoirs for food-borne pathogens such as shigella toxin-producing E. coli and pathogenic Salmonella. If researchers can better understand how a host’s genetic makeup influences the development of its gut microbiota, it’s possible they could then develop interventions to boost beneficial bacteria while mitigating harmful ones.

But this research may also offer broader insights into the intricate set of factors that culminate in human metabolic syndromes, intestinal disorders and even cancers. “The gut microbiome has various functional roles for human health,” Jeong says. “Our findings could lead to the establishment of new targets not only for GI tract dysbiosis but also possibly for cancer treatment.”

By: DeLene Beeland