Gut bacteria linked to obesity-related health problems

The answer to why some obese people develop diabetes and other health problems may be found not in just a love for junk food, but in the bacteria that thrive deep in the human gut.

Scientists at the University of Maryland School of Medicine have identified 26 species of intestinal bacteria linked to insulin resistance and the high blood pressure, cholesterol and sugar levels suffered by the obese. These preventable conditions often lead to potentially fatal health problems including stroke, heart disease and diabetes.

The researchers don't understand yet how the bacteria in the gut, or intestines, interact with the human body to manifest into illness. But they say identifying the harmful microorganisms from among the trillions that coexist harmoniously in the human body is a major step toward one day developing new treatments for one of the country's most pressing medical issues.

"We can't infer cause or effect, but now that we have results from step one and we can now look at what the bacteria are doing, it can give us more information to go about getting an intervention," said Dr. Brandi Cantarel, a research associate at the University of Maryland Institute of Genome Sciences who worked on the study.

The study is one in a growing field of research looking at how the bacteria, fungi and viruses that live on every inch of the body — known collectively as microbiome — play a role in human sickness. They outnumber human cells 10 to one.

The National Institutes of Health Human Microbiome Project, launched in 2008 with a $115 million budget, gave birth to dozens of studies around the country including the University of Maryland's obesity research to try to find the answer. The study was published this month in PLOS ONE, a journal of the Public Library of Science.

"The big question is how these microorganisms affect health and disease in humans," said Dr. Alan R. Shuldiner, an associate dean of the program in personalized and genomic medicine at the University of Maryland School of Medicine.

Since the project's launch, studies have found links between microorganisms and flu in young children, the digestive disorder Crohn's disease and the skin disorder psoriasis, among others. A recent study also found a link to cancer.

Humans pick up these microbes from the environment, with the first coming from the mother's birth canal during delivery. Over time newborns start to develop their own microbes.

"People have known for a long time the body is full of microorganisms and now the tools have become available to study them," said Lita Proctor, coordinator of the NIH Human Microbiome Project.

Researching microbes has become easier with sequencing of the microbial DNA, much like the sequencing of the human genome, enabling scientists to study the organisms by their genetic signature. Before scientists grew microbes in the lab, a much more time intensive and complicated process. Early studies were done in mice, but those results aren't always directly applicable to humans.

The University of Maryland scientists analyzed microbes taken from stool of the Amish in Pennsylvania. The population is easy to study because it is very homogenous, creating fewer variables, such as diet and lifestyle, that may affect results. They descend from a few founding families and have similar lifestyles.

"You won't find people who are widely different, like vegans and meat eaters," Cantarel said. "You're not going to find people who smoke two packs a day and who don't."

Participants in the study varied in age, weight and size.

Gene markers were used to distinguish between the different bacteria found in the stool taken from 310 Amish. Researchers found everyone in the study had one of three different communities of bacteria. The guts of people with high blood pressure, insulin resistance and other so-called metabolic syndrome diseases related to obesity also had 26 other rare bacteria.

The study also used the data to see if a person's occupation was associated with microbes in the gut. They found farmers and others who had regular contact with animals had bacterial communities also common in the livestock.

The Maryland researchers now hope to find funding to take the next step and explore the different ways the microbes may be interacting in the body.

There could be a myriad of explanations, researchers say.

"We think the answer to that question is probably complicated and multifaceted," Shuldiner said. "It may have something to do with genes, or various lifestyle factors and the environment. We just don't know."

For instance, do the microorganisms produce some byproduct that causes metabolic syndrome?

The University of Maryland study also found a link between obesity and inflammation, which is believed to be a factor in obesity and other chronic conditions. They found that people with metabolic syndrome with serum markers associated with inflammation had low levels of good bacteria known to have anti-inflammatory properties.

Proctor suggested that perhaps the metabolic functions of the microorganisms somehow influence the metabolic functions of the human body. The microorganisms have their own biological processes and genome. In the gut, the bacteria are supplied with nutrients that humans ingest.

Further study could lead to new treatments, that could target the microorganisms with medication or changes in lifestyle and diet that may influence how the microorganisms behave in the body.

"The end goal could be all kinds of things," Proctor said.

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