Researchers at Harvard’s Wyss Institute have developed a living bacterial hydrogel that can adhere to lesions in the gut wall to encourage healing and reduce inflammation. Consisting of genetically engineered bacteria that produce nanofibers that adhere to mucus, the resulting hydrogel could function as a novel probiotic therapy for inflammatory bowel disease.
Approximately 1.6 million people in the US have incurable inflammatory bowel disease, in which immune dysregulation and microbial factors in the gut contribute to lesions and inflammation in the gut lining. At present, anti-inflammatory drugs and antibiotics are often used to treat such conditions, but these can have serious side-effects. Antibiotics can also further disrupt the gut microbiome, leading to a variety of problems, including drug resistance.
These researchers have developed a new type of therapy for inflammatory bowel disease, which uses genetically modified bacterial hydrogels to shield lesions in the gut and promote healing. “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 Neel Joshi, a researcher involved in the study. “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.”
The bacterial hydrogels can be ingested orally, and will travel through the gut before adhering to a lesion. The bacteria secrete a modified protein that binds to mucus and forms nanofibers on the bacterial cell surface. This results in a water-infused mesh, which is the major component of the hydrogel. As the gel is created by the bacteria within it, it is self-regenerating. So far, the researchers have tested the gels in a mouse model of inflammatory bowel disease, with promising results.
“When we induced colitis in the colons of mice by orally administering the chemical dextran sodium sulfate, animals that had received the PATCH-generating E. coli Nissle strain by daily rectal administration starting three days prior to chemical treatment, had significantly faster healing and lower inflammatory responses, which caused them to lose much less weight and recover faster compared to control animals,” said Pichet Praveschotinunt, another researcher involved in the study. “Their colon epithelial mucosa displayed a more normal morphology and lower numbers of infiltrating immune cells.”
Study in Nature Communications: Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut
Via: Wyss Institute