How preventing bacteria from escaping the gut could treat autoimmunity
A trio of Science papers shows a leaky gut can drive systemic inflammation and autoimmunity by allowing bacteria and their products to escape the GI lumen and enter the bloodstream. The results open a variety of therapeutic options for sealing the leak or clearing the out-of-place bacteria, all of which should avoid the side effects of marketed immunosuppressants.
Normally, a healthy gut doesn’t let excess levels of bacterial products exit the confines of the gut to wreak havoc on surrounding tissues. Epithelial cells in the intestine form tight intercellular junctions that create a solid barrier to limit passage of macromolecules into the systemic circulation.
Although deterioration of the junctions is associated with inflammatory bowel disease (IBD) and a growing list of other autoimmune and inflammatory disorders, little has been learned about the molecular mechanisms linking gut leakiness to disease, according to Ramnik Xavier, lead investigator on one of the new papers. Xavier is chief of gastroenterology at Massachusetts General Hospital, and co-director of the infectious disease and microbiome program at the Broad Institute of MIT and Harvard.
Marketed drugs for autoimmune diseases work by blanket immunosuppression, which increases the risk of infections and cancer.
All three of the new papers make inroads into the molecular mechanisms of gut leakiness and suggest strategies for avoiding the liabilities of broad immune suppression.
Xavier’s study tracks the function of the IBD-linked gene C1orf106 to maintenance of barrier integrity, and shows the pathway it regulates could yield new targets for IBD.
Before his paper, “nobody had identified genetic