About 1.6 million people in the U.S. have an incurable inflammatory bowel disease (IBD) such as Crohn’s or ulcerative colitis, and 70,000 new cases are diagnosed each year.
IBD patients suffer from pain, extreme discomfort, and numerous other symptoms caused by continuously relapsing and remitting inflammatory lesions in the layer of cells that lines the intestinal lumen (mucosa). The exact causes for IBD still are poorly understood, but it is clear that a misdirected immune system is at work, and that certain components of the microbial community in our gut, known as the intestinal microbiome, and environmental factors contribute to its destructive forces.
While anti-inflammatory drugs can dampen acute inflammation and antibiotics can fight local infections when IBD episodes flare up, their use also comes at a cost. Anti-inflammatory drugs can have severe side effects, and antibiotics can disrupt the beneficial parts of the microbiome. Importantly, there are no wound treatments available that could be applied to inflamed lesions directly from inside the gut lumen in order to speed up healing and minimize use of those drugs.
Now, a research team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by Neel Joshi has developed a living-material approach that uses a strain of genetically engineered E.coli Nissle gut bacteria as a locally acting probiotic. The engineered bacteria produce a network of nanofibers that directly binds to mucus to fill inflamed areas like a patch, shielding them from gut microbes and environmental factors. This probiotic-based therapeutic strategy protected mice against the effects of colitis induced by a chemical agent and promoted mucosal healing. Their findings are reported in Nature Communications.
“With this ‘living therapeutics’ approach, we created multivalent biomaterials that are secreted by resident engineered bacteria on-site and attach to many mucus proteins at a time — firmly adhering to the viscous and otherwise moving mucus layer, which is a challenging thing to do,” said Joshi. “The Probiotic Associated Therapeutic Curli Hybrids (PATCH) approach, as we named it, creates a biocompatible, mucoadhesive coating that functions as a stable, self-regenerating Band-Aid and provides biological cues for mucosal healing.”