Study shows how gut microbiota interact with genes to promote Crohn’s disease.
Genetic susceptibility is thought to play a role in common diseases including those affecting the colon such as inflammatory bowel diseases (IBD) and colorectal cancer. As is the case for genomic variants in general, a number of these variants are located in gene deserts and their functional roles in disease pathogenesis are largely unknown. Now, a study from researchers at Cedars-Sinai shows that a major type of IBD may be caused in part by genetic variants that prevent beneficial bacteria in the gut from doing their job. The team state that their findings identify a completely novel mechanism through which these genes may lead to an increased risk of developing Crohn’s disease. The study is published in the journal Science.
Previous studies show that bacteria historically have been regarded as an enemy of the body, however, more recently bacterial types have been identified as beneficial to health, especially in the case of IBD. The current study shows the beneficial effects of Bacteroides fragilis bacterium, one of billions of microscopic organisms that normally inhabit the human gastrointestinal system, were negatively impacted by variations in the ATG16L1 gene.
The current study utilised both a mouse model and human specimens for Crohn’s disease. Results show that genetic variations in the ATG16L1 gene increases the risk of developing Crohn’s disease, one of the two common forms of IBD. Data findings show that the bacteria were prevented from carrying out one of their critical functions, namely, suppressing inflammation of the intestinal lining.
The lab explain that patients with Crohn’s disease suffer from inflammation of the gastrointestinal tract, often resulting in severe abdominal pain and weight loss as well as symptoms outside the gut, including arthritis. They go on to add that given the low percentage of IBD patients who respond to drugs directed at the immune system, their results could point the way to improving treatment by identifying patients who might best respond to manipulation of bacteria in their digestive tract.
The team surmise that their findings have implications for treating Crohn’s disease as well as other immune disorders that share similar genetic variations. For the future, the researchers state their work is a critical step in developing specific therapies that can provide more effective and precision treatments for patients.