Microbes that colonize the gut likely play a role in inflammatory bowel disease (IBD)—but perhaps not as directly as scientists suspected.
A new study with mice suggests bacteria produce small particles that can get into the lining of the gut and provoke an aggressive response from the immune system.
“You can compare these particles, which are known as vesicles, to fighter jets being released from a bacterial mothership,” says study coauthor Christina Hickey, a clinical fellow at Washington University School of Medicine in St. Louis. “Having a more accurate picture of how these jets trigger the onset of an attack should help us devise better ways to help prevent IBD symptoms.”
The findings, published in Cell Host and Microbe, highlight a bacterial enzyme that could be a target for IBD treatments.
As part of the study, coauthors Thad Stappenbeck and Paul Allen, both professor of pathology and immunology, worked with mice they genetically altered to develop a condition similar to very early onset IBD. This disorder, which can cause more severe symptoms than adult forms of the disease, typically is diagnosed before age 6. It often is caused by rare genetic mutations.
‘We didn’t realize this was possible’
With Eric Martens of the University of Michigan, the researchers studied a bacterial species known to cause colon inflammation in the mice. They suspected that Bacteroides thetaiotaomicron (B. theta) degrades the mucus that lines the interior of the gut, enabling the bacteria to enter the gut tissue, encounter immune cells, and provoke an immune response that leads to the intestinal inflammation that characterizes IBD.
Instead, to their surprise, they found that the bacteria remain in the gut, while vesicles made by the bacteria make their way into the gut tissue. These vesicles are tiny spherical pockets that pinch off from the bacteria’s outer membranes.
The vesicles travel from the bacteria into the tissue of the host, where they interact with the immune cells.
“The immune cells don’t need to encounter the bacteria to cause inflammation—all they need to do is encounter the vesicles,” Stappenbeck says. “We didn’t realize that was possible, and we think this discovery could change our thinking about not just IBD but other autoimmune disorders and infectious diseases.”
The research showed that the contents of the particles included a bacterial protein that causes inflammation. According to the scientists, a drug that blocks this protein might help prevent vesicles from leaving the gut and contributing to IBD.
The National Institutes of Health supported the research.