SCI adv: new research to help the treatment of intestinal diseases

February 15, 2020 / BIOON / -- each of us carries about 38 trillion bacteria in our intestines How can such a veritable "microbial zoo" live peacefully in our intestines without triggering an immune system attack? The answer lies in the intestinal mucosal barrier, which consists of closely connected epithelial cells arranged on the intestinal wall, a dense layer of mucus (which can protect these cells from bacteria and other intestinal contents) and immune cells under the epithelial cells, which can quickly kill any infiltrating microorganisms When the mucosal barrier is destroyed, friendly bacteria become enemies as the immune system reacts to their inflammation This inflammation can hinder the healing process of the mucosal barrier, thus prolonging the contact between intestinal microorganisms and immune cells and forming a malignant feedback loop This long-term immune response to the gut can lead to many health problems, including infection, food allergy, diabetes, liver disease, nervous system diseases, cancer and inflammatory bowel disease (IBD), which bring heavy burden to patients In response, scientists at the Wyss Institute are exploring various strategies to overcome this problem and effectively cure the mucosal barrier, which can alleviate the suffering of millions of patients around the world (image source: www Pixabay Com) Dr Elliot chaikof, associate professor of Wyss college, decided to try to solve the problem from different perspectives In a recently published paper, chaikof and his team focused on the protein aromatics receptor (AHR), which is known to change the expression patterns of some immune related genes when activated, and the inactivation of the protein can cause mucosal barrier dysfunction The researchers synthesized a series of compounds with structures similar to those known to activate AHR, and then combined with experiments and computer simulation to identify candidate compounds showing strong AHR binding power After several rounds of design and refining of candidate compounds, the team looked at two of the most promising compounds, py108 and py109, respectively When they introduced these compounds into human and mouse intestinal cells, they found that AhR activation levels increased, significantly improving animal health and survival There are other positive benefits in py109 treated mice, including up regulation of IL-22 and IL-17A genes, which are known to enhance mucus production and support barrier cell function When the compound was tested on T cells from patients with or without IBD, cell populations from both patients showed elevated levels of IL-22, suggesting that py109 may be useful in regulating the immune system, thereby helping to cure mucosal symptoms Source of information: using the immune system, hydraulics, and bacteria to treat and prevent internal diseases source: Jiaxuan Chen et al Modification of lymphyte mediated tissue repair by rational design of ergonomic ary hydrogen receiver countermeasures, science advances (2020) Doi: 10.1126/sciadv.aay8230