New Research Pinpoints Genetic Variation That Can Reduce Gut Bacteria And Lead To Disease

Aug 10, 2016

Changes in gut bacteria have been linked to Crohn's disease, obesity, schizophrenia, type 2 diabetes, Alzheimer's disease and other conditions.
Credit Courtesy of Pacific Northwest National Laboratory

The healthy human gut is home to hundreds of millions of bacteria species.

But people who are missing a few hundred or so particular species are at greater risk for certain health issues, including Crohn’s disease, which is characterized  by chronic inflammation of the bowels. 

Richard Duerr, a professor at the University of Pittsburgh School of Medicine, is co-senior author of a study linking that lack of gut diversity with a specific genetic variation.

Duerr said researchers have long known that  Crohn’s was associated with reduced diversity in the microbiome. They also knew that a variation in the SLC39A8 gene is linked with obesity, schizophrenia, cholesterol levels and blood pressure.

“All of those conditions had previously been associated with changes in the gut microbiome, so we wondered whether this genetic variant changed the gut microbiome and … whether the changes in the gut microbiome could confer risk for these various disease states,” Duerr said.

Essentially, Duerr said, it was a chicken and egg problem. Did Crohn’s disease alter the gut microbiome or did an altered gut microbiome lead to Crohn’s disease?

“The fact that we found that this genetic variant, which is associated with inflammatory bowel disease and also with these other disease states, is associated with changes in the gut microbiome suggests that in fact the genetic variant is altering the composition of the gut microbiome and then that’s conferring risk for these disease,” Duerr said.

Duerr said the next step is to sort out how this particular genetic variation actually affects gut bacteria diversity. He said the gene codes a protein involved in transporting zinc and that zinc deficiencies can affect immune responses, which in turn could affect the gut microbiome.

Researchers found that about 7 percent of healthy people carry this particular genetic variant, while about 10 percent of Crohn’s patients carry it.

“It’s actually thought to be an interaction between the genetic variants … and environmental influences that lead to many common, complex diseases,” Duerr said.

Academic interest in understanding how micro-organisms living inside our bodies affect human health has been growing over the past decade. The National Institutes of Health launched the Human Microbiome Project in 2008. In May, the University of Pittsburgh announced the creation of a new Center for Medicine and the Microbiome to help accelerate this research and develop potential therapies.

“There is emerging evidence that some of these changes in the microbiome probably do predispose to disease, and that means targeting the gut microbiome for manipulation could help us treat human diseases,” Duerr said.

The Crohn’s and Colitis Foundation of America estimates that about 700,000 Americans are affected by Crohn’s disease.

Dermot McGovern, director of Translational Medicine at the Cedars-Sinai Inflammatory Bowell and Immunobiology Research Institute in Los Angeles, was co-senior author of the study, which will be published in October in the journal Gastroenterology.