Genetic Variant Associated with Crohn’s Disease Linked to Altered Gut Microbiome

Genetic Variant Associated with Crohn’s Disease Linked to Altered Gut Microbiome

A team led by scientists at the University of Pittsburgh, Cedars-Sinai Medical Center, and the University of California Los Angeles (UCLA) found that a genetic variation associated to blood pressure, obesity, cholesterol levels, and schizophrenia is also linked to Crohn’s disease.

The study titled “A pleiotropic missense variant in SLC39A8 is associated with Crohn’s disease and human gut microbiome composition,” published in the journal Gastroenterology, also reveals that the genetic variant is associated with alterations in gut microbiome.

“We knew from previous studies that there is reduced diversity of the gut microbiome in patients with Crohn’s disease,” said co-senior and corresponding author Dr. Richard Duerr, a professor in Pitt’s School of Medicine, and co-director and scientific director of the UPMC Inflammatory Bowel Disease Center in a news release. “But that left us with a question: Does Crohn’s disease alter the composition of the gut microbiota, or do pre-existing changes in the gut microbiota confer risk for Crohn’s disease?”

Duerr said the study found a reduction in the abundance of hundreds of minor species of gut bacteria in healthy, overweight and Crohn’s disease-affected people who carry the genetic variant —  which suggests that the genetic variant may increase risk for disease by altering the gut habitat.

“This is an important step toward understanding how the disease works so we can develop therapies or a cure in the future,” Duerr said.

Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis (UC), are chronic relapsing inflammatory conditions of the gastrointestinal tract. Both are significant causes of morbidity and have estimated direct and indirect costs of $6 billion annually in the United States.

Currently, the etiology (cause) and pathogenesis (development) of IBD are not fully understood, but it is widely accepted that genetic factors play an important role. Common variant genome-wide association studies have identified 200 IBD-associated loci (specific location of a gene on a chromosome).

The team of researchers analyzed 10,523 blood samples from people with IBD and 5,726 samples from healthy people, and found a variation in the SLC39A8 gene related to Crohn’s disease.

“This finding is another important example of how a particular genetic variant can have a role in the development and course of many diseases. Our study of this variant suggests that therapies effective in treating one disease also may benefit the treatment of some patients with other illnesses,” said Dr. Dermot McGovern, PhD, director of Translational Medicine in the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute.

Co-senior author Dr. Jonathan Braun, PhD, chair and professor of pathology and laboratory medicine in the David Geffen School of Medicine at UCLA, said many of the species are believed to play key roles in protecting the intestines against Crohn’s disease and promoting a lean bodies.

“So, this may be an example where the gene increases risk for disease via its effect on types of bacteria we need to preserve our health,” Braun said.

According to Duerr, the discoveries raise questions and potential research paths. To accelerate research and the potential development of therapies, the University of Pittsburgh recently established its Center for Medicine and the Microbiome.

“This study illustrates the remarkable interaction between our proper genome and our symbiome—the organisms and environment inside and outside of us that influence our well-being—in the setting of inflammatory bowel disease,” said Dr. Mark T. Gladwin, chair of medicine. “Insights from this study are likely to guide the development of microbiome modulating therapies that hold the promise to alleviate patient suffering.”

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