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Bacterial Hydrogel Adheres to Gut to Treat Inflammatory Bowel Disease

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.”

These images show histological cross sections of colon from mice used as a disease model for colitis. The colons of injured mice (middle) lose the characteristic columnar cell structure of the healthy gut (left). When treated with PATCH, the mouse colons were able to maintain a healthy morphology even in the presence of inflammatory insults. Credit: Wyss Institute at Harvard University

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



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