Human DNA influences gut bacteria

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Melissa Osgood

Our DNA influences everything from eye color to disease risk, but it also somehow affects how microbes colonize our bodies. A Cornell-led study published May 11 in the journal Cell Host & Microbe provides the strongest evidence yet that human DNA influences the type and number of bacteria that reside in each person’s gut.

At birth, thanks to the sterility of the womb, humans generally have no microbes in their bodies. Infants however are quickly colonized through breastmilk, food and their environment. But which microbes colonize a person’s gut, and how abundantly, can be strongly influenced by human DNA, according to the study’s 10 authors, including Ruth Ley, associate professor of microbiology, and Andrew Clark, the Jacob Gould Schurman Professor of Population Genetics and a Nancy and Peter Meinig Family Investigator.

The findings provide new evidence about how DNA shapes the constituency of microbes inside of us just as research reveals the extent to which those microbes impact our health.

The interactions between microbes, genetics and diet in the human microbiome are complex, said lead author Julia Goodrich, a doctoral student and National Science Foundation Graduate Research Fellow in Ley’s lab.

Microbial colonies in the gut play an important role in aspects of human health that include risk of obesity and the ability to break down lactose, Goodrich said.

“Now we’re starting to see more and more that the host also influences the microbiome,” she said.

“Our genes might influence which microbes persist in the gut and which are more dominant than others. Diet also influences the microbiome, and our genetics can even influence our diet preference and taste perception. They all seem to be interrelated, and our genes impact which microbes thrive inside us to a degree to which we didn’t know until recently,” she said.

In order to study genetic versus environmental influences on the microbiome, the researchers looked at genotyping data of identical and fraternal twins held by King’s College in London as part of the TwinsUK registry. Then they studied fecal samples to determine how similar the gut bacteria were among twins who were genetically identical versus fraternal twins raised in the same environment.

The current research builds off a previous 2014 study from Goodrich, Ley and their co-authors. That paper found that the bacterial family most strongly influenced by a person’s genetics was Christensenellaceae, which was also found in much greater abundance in the guts of lean people versus heavier people.

For the new study, the authors nearly tripled their datasets to 1,126 twin pairs, and expanded to 945 widely shared microbes or microbe families. They found that 8.8 percent of the microbes they studied were influenced by their host’s genes, and confirming their previous results, Christensenellaceae is still the most heritable.

“We found Christensenellaceae in at least 97 percent of individuals, and I think it’s probably in everybody,” Goodrich said. “Your genetics aren’t actually playing a role in whether you get the bacteria, but your genetics do play a role in what levels you have in your gut.”

Another bacterium that shows a strong genetic link is Bifidobacterium. People with variants on the gene LCT – which influences whether people can break down lactose, the milk sugar – have more Bifidobacterium in their guts.

“Bifidobacterium can utilize lactose. We think that if it’s not broken down before it reaches them in the large intestine, they flourish,” Goodrich said.

These Cornell-led studies have been unique in combining the fields of microbiome research with genetics, and this is the largest study of its kind so far, Goodrich said.

The study’s co-authors also include Emily Davenport, a postdoctoral associate in Andrew Clark’s lab, and researchers from King’s College London, University of California, San Diego, and the University of Chicago.

Krisy Gashler is a freelance writer for the College of Agriculture and Life Sciences.


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