Ulcerative colitis, a form of inflammatory bowel disease (the other type being Crohn’s disease), affects a reasonable number of Americans. Being a chronic condition, it is associated with a significant decline in the health status of these individuals. It is believed to be a result of disruption in the microflora of the gut although there exists evidence that there may be a genetic undertone to its development.
Treatment options for this condition before now have focused on immunosuppression, nutrient supplementation, and nicotine therapy none of which target specifically the gut microorganism that may be causally related to the disease. However, owing to recent research findings, the health community may be on its way to getting a more targeted treatment option for this condition.
What was done?
Researchers at the University of California San Diego School of Medicine, David J. Gonzalez, Ph.D., and Rob Knight, Ph.D., in a study published in Nature Microbiology on January 27, 2022, identified what they believe to be the driving agent of ulcerative colitis – a microbial enzyme class called proteases. Gonzalez is an associate professor at Skaggs School of pharmacy and pharmaceutical sciences and UC San Diego School of Medicine while Knight is a professor and director of the Center for Microbiome Innovation at UC San Diego.
To carry out this study, they obtained stool samples from patients with ulcerative colitis, digitized it, and observed that about 40 percent of the patients show overexpression of proteases – enzymes that digest or break down proteins. Their findings revealed that these enzymes were expressed by the gut microflora Bacteriodes vulgatus. To further confirm their findings, they transplanted protease-rich stool from patients with this inflammatory bowel disease into germ-free mice, and these in turn induced ulcerative colitis in them. They hypothesized that adverse or stressor conditions in the gut like nutrient deprivation caused increased expression of the proteases in a bid to utilize proteins as an alternate source of nutrition. These proteases expressed in turn damage the intestinal epithelium, allowing the increased entry of immune cells which propagates the inflammatory destruction of the gut lining that characterize the condition.
Although several studies in the past have shown correlations between gut health and microbial constitution, none have been able to identify a particular organism with a causal relationship or how the organisms are implicated in the pathogenesis. According to Prof. David J. Gonzalez, “this is the first study with evidence that is based on experimental findings that pinpoint a specific microorganism driving ulcerative colitis, the protein class it produces and a promising solution”.
This study has opened promising treatment strategies for ulcerative colitis as protease inhibitors can be used to block the damaging effects of these enzymes. Aside from treatment, this study also holds great potential for clinicians as antibody tests can be used to ascertain patients that may benefit from protease inhibitors.
Ulcerative colitis has for a long time been a source of significant morbidity to those affected. It is the hope of the scientific community that further investigation into the role of proteases in its pathogenesis will pave the way to more effective treatment options.
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