10 December 2019

Probiotic patch

Scientists have created a gel for healing intestinal wounds

Vladimir Kuznetsov, Hi-News

Inflammatory bowel diseases are one of the most common pathologies on our planet. According to official statistics, several billion people have various intestinal problems, including Crohn's disease, ulcerative colitis, duodenal inflammation, and so on. According to scientists from Harvard University, only in the USA about 70,000 new cases of inflammatory bowel diseases are registered per year. However, a new remedy is designed to correct the situation, a gel that separates the problem area from the aggressive environment of the intestine, promoting tissue regeneration.

Why do inflammatory bowel diseases develop

The exact causes of the most common diseases of this kind are still poorly understood, but it is believed that the wrong work of the immune system plays a leading role in this process. Inflammatory lesions destroy epithelial cells that function as a barrier. This loss of barrier function leads to a kind of cycle: inflammation provokes even greater destruction of the barrier, and the destruction of the barrier leads to the progression of inflammation.

A new gel created by scientists from Harvard University helps to maintain the barrier function of the intestine even in the presence of inflammatory lesions. Animal experiments have shown that the drug, like a patch, closes intestinal wounds and promotes healing of the mucous membrane. At the same time, existing methods of therapy for such conditions are expensive and not always effective. For example, the standard for today is the use of anti-inflammatory drugs and antibiotics that will fight infections, which are often "companions" of such lesions. But anti–inflammatory drugs can have serious side effects on the entire body as a whole, and antibiotics are able to destroy the existing beneficial microflora, on which many functions also depend - from digestion to the production of certain vitamins.

But a research team from Harvard University, led by Dr. Neil Joshi, has developed a new approach. The already mentioned gel contains a strain of genetically modified intestinal bacteria E.coli. Their uniqueness lies in the fact that they produce a network of nanofibers that directly binds to intestinal mucus in order to fill inflamed areas, protecting them from intestinal microbes and aggressive intestinal environment factors.

mucosal-healing.jpg

Inflammation destroys epithelial cells that function as a barrier between the intestinal lumen and its wall (left). The loss of barrier function leads to a feedback loop of exacerbation of inflammation caused by bacteria and other particles crossing the barrier. Biologically active material synthesized by artificial probiotic bacteria helps to maintain the barrier function of the intestine even in the presence of inflammatory lesions, thereby helping to retain bacteria and other particles in the lumen and easing the symptoms of inflammation (right) – VM.

With the help of our "bacterial therapy" approach, we have created unique biomaterials that are produced by special bacteria and attached to the walls of the intestine, while firmly adhering to a viscous and moving layer of mucus. This is a challenging task. We called this method The Probiotic Associated Therapeutic Curli Hybrids (PATCH) – say the authors of the work (Praveschotinunt et al., Engineered E.coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut, published in the journal Nature Communications – VM).

In order to create a unique gel, a team of scientists programmed a laboratory strain of E.coli to synthesize and secrete a modified CsgA protein. It has the necessary properties, but the problem is that it begins to act only in the environment of the intestine. Therefore, it needs to be developed "on the spot". For this purpose, a genetically modified strain of bacteria is included in the new drug. 

At the same time, in the course of research, we found that bacteria, even when taken orally, also colonize and live in the intestinal tract, so the drug will be extremely convenient for patients.

Scientists believe that their approach can be used as a concomitant therapy method. It can be used in addition to existing anti-inflammatory and antibacterial methods, as well as treatment regimens in which the activity of the immune system decreases (which, as already mentioned, is considered a leading factor in the development of inflammation). In this case, additional protection of the intestines with gel comes in handy.

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