People’s genes welcome their microbes

In mice and humans, genetic variants seem to control the bacterial mix on and in bodies

BOSTON — Humans may be in charge of which bacteria live in and on them, researchers report. Scientists used to think that what people ate and where they lived were the main determinants of the microbes that colonize human bodies, but the new studies suggest the immune system selects its microbial companions. Paradoxically, that control may make it harder to change which microbes call a person’s body home.

Studies of mice and humans presented at the annual meeting of the American Society of Human Genetics indicate that the genetic makeup of the host determines which microbes set up shop in the intestines, on the skin and in other parts of the body. And a paper appearing October 29 in Genome Research finds that people with immune disorders host a wider variety of bacteria and fungi, some pathogenic, on their skin than do healthy people.

The set of microbes that live in and on a host organism — known as the microbiome — is highly individual, said Andrew Benson, of the University of Nebraska-Lincoln, at the meeting. Even mice that live in identical controlled conditions may have widely varying microbiomes.

To find out why people and animals develop a certain microbiome, Benson and his colleagues studied the microbes of genetically diverse mice. When the researchers characterized which types of bacteria lived in the intestines of the mice, they saw “a shotgun blast of diversity,” Benson said October 23.

Which microbes are present may not be as important as what they do for the host, so Benson’s team determined the functions of the bacteria. They found that some genetic variants in the mice went along with bacteria that make amino acids important for communication between immune cells. Mice with variants in proteins that sense certain amino acids tended to have more bacteria that produce those same amino acids, the team found. Variants in some of the mice’s immune system genes were also associated with particular microbial mixes. The mice’s own genes seem to encourage the growth of some microbes while discouraging others, Benson said.

“It’s beautiful work,” said Ran Blekhman of the University of Minnesota, Twin Cities. Blekhman has come to similar conclusions using data gleaned from the human microbiome project, an effort to catalog people’s microbes (SN: 6/16/12, p.15).

Blekhman reported October 24 that he and his colleagues found that the more similar two people’s genetic makeups are, the more similar their microbiomes. Human genes involved in regulating the immune system are associated with the types of microbes that set up shop in a person. That may mean that the human immune system picks and chooses its bacterial buddies. People with genetic variants that affect an appetite-controlling hormone called leptin or with variants in genes associated with colon cancer also harbor different mixes of microbes, he found, indicating that microbes may work together with human genes to produce obesity, some types of cancer or other diseases.

In the Genome Research report, dermatologist Heidi Kong at the National Institutes of Health in Bethesda, Md., and colleagues compared the microbial communities on the skin of 49 healthy people to those on 41 people who have rare immune system disorders that make them prone to eczema-like skin problems. The patients had one of three disorders, each of which is caused by a defect in a single gene.

Kong and her colleagues found more variety in the microbial populations on the immune-deficient patients’ skin, suggesting that functional immune systems usually govern microbes on the skin. She thinks that having a haphazard collection of microbes may increase a patient’s’ risk of infection. If true, doctors could develop treatments that, rather than killing off specific germs with antibiotics, restore a healthy balance of microbes.

But a problem for people hoping to improve health by altering their microbiome is that a person’s genes don’t change. If human genes control which microbial companions can live on the body, that could mean altering the microbiome might be difficult, the researchers said. For instance, introducing beneficial bacteria through eating yogurt or taking dietary supplements called probiotics might be for naught if the immune system is set against those microbes. Plus, new bacteria may have a hard time taking hold in an already thriving microbial community, Benson said.

“Giving a probiotic is like introducing a new species into a rainforest,” he said.

Previous studies have indicated that diet, antibiotics and some other environmental changes may shift the microbe mix temporarily, but by adulthood, the microbiome is usually quite stable. The new studies may help explain that finding.

Researchers still have a lot to learn about how the microbiome develops and how it influences health, Blekhman said. But knowing how human genes interact with bacteria and other microorganisms may eventually lead to therapies that could manipulate microbiomes.

Additional reporting by Beth Mole.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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