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Over the past two years, The Akkermansia muciniphila in the gut microbes has become a star bacteria that plays an important role in the fight against obesity, type 2 diabetes and aging, and has even been supported by human trialsMost amazingly, for Akk, it always seems to be "hot and eat" more effectiverecently, researchers from Nanjing Medical University have made a similar discovery, they have demonstrated in mice, oral inactivated Akk bacteria or Akk bacteria epithelial protein Amuc_1100, can be regulated CD8 plus cytotoxic T cells (CTL) to improve colitis, and prevent the occurrence of related bowel cancer! The study was published in the journal GutAkk (Photo: microbiology.org)The researchers first collected stool samples from patients with ulcerative colitis, intestinal adenomas and bowel cancer from the Central Hospital of Jiangsu ProvinceThe results of 16S rRNA sequencing showed significantly lower levels of Akk bacteria in fecal feces in three groups of patients than in the fecal microbiome of healthy volunteers, like human patients, the abundance of Akk bacteria decreased in mice with colitis and colitis-related bowel cancer induced by sodium glucoolite sulfate (DSS), and the abundance of Akk bacteria decreased gradually in a time-dependent manner during tumor developmentnext, the researchers tried to give the mice with colitis oral supplements to the inactivated Akk bacteria and Amuc_1100 proteins of the pasteurized method (70 degrees C, 30min), Amuc_1100 a protein isolated from the outer membrane of The Akk bacteria, which, unlike bacteria, remained active at a "high temperature" of 70 degrees Cresearchers found that supplementation with Akk and Amuc_1100 did not improve the weight loss caused by colitis in mice, but significantly reduced the amount of activity in the onset of the disease, and reduced colon shortening, colon tissue damage and spleen swellingThe inflammatory factors of TNF-alpha, IFN-pyridine, IL-1 beta, IL-6, IL-8 and L-33 were also significantly reduced in miceThis suggests that colitis in mice did be alleviatedwas less active in mice with Akk bacteria (blue) or Amuc_1100 (purple) than the control group (red
From the above indicators we can also see that the level of inflammation in mice significantly decreased, as an immune disease, which certainly behind the end of the immune responseTo understand how Akk and Amuc_1100 regulate immune response, the researchers examined the ratio of CTL and macrophages in micein the spleen and colon of colitis mice, the proportion of CTL increased significantly, indicating that the immune response was very strong, while oral Akk bacteria and Amuc_1100 reduced the proportion of CTL and pro-inflammatory CD16-CD32 plus macrophagesNot only that, as we know, there is pD-1 on the CTL called the "brake molecule", and the proportion of CTL expression PD-1 is reduced in mice with colitis, and after treatment, it is also recoveredulcerative colitis and Crohn's disease are known risk factors for bowel cancer, and for every 10 units of the patient's inflammatory burden index, the risk of bowel cancer increases by 2.1%So controlling inflammation means reducing the risk of bowel cancer in patients, and Akk and Amuc_1100 do it, without using any drugs, simply supplemented with Akk bacteria and Amuc_1100 significantly delayed the occurrence of bowel cancer in DSS-induced colitis mice, and the number and area of tumors were relatively smallazooxide methane (AOM) and DSS induced bowel cancer in mice, D for intestinal anatomy in mice, and E for weeks 12 and 23 of the tumor number of statistics
At the molecular level, the addition of Akk bacteria and Amuc_1100 reduced the expression and lysis of the expression of h2AX in the colon epithelial cells and the lysate of the caspase3 enzyme, which indicates that the colon epithelial cells apoptosis and double-stranded DNA fracture decreased, while the expression level of ki67 decreased, indicating that abnormal cell proliferation inhibitionit can be seen that Akk bacteria and Amuc_1100 can prevent the occurrence of bowel cancer by reducing DNA damage, reducing apoptosis and inhibiting abnormal proliferationwe mentioned earlier, Akk bacteria and Amuc_1100 can regulate the immune response, in the prevention of bowel cancer, they actually play this advantage, but this time the adjustment is the intestinal membrane lymph nodes in the CTLIn intestinal membrane lymph nodes, CTL increased and CTL expressed for PD-1 decreased, and these changes showed an increased cytotoxiceffecteffecteffect effect of CTL on bowel cancer cells in the lymph nodes of the intestinal membranein general, Akk bacteria as a beneficial bacteria, will be gradually reduced with the development of enteritis, supplementing Akk bacteria or its outer membrane protein Amuc_1100 can reduce enteritis symptoms, regulate the spleen, intestines and intestinal membrane lymph nodes in the immune response, reduce the level of inflammation in the intestine, prevent enteritis caused by bowel cancer, bowel cancer has become the fourth leading cause of cancer-related deaths worldwide, with bowel cancer accounting for a significant proportionthere has been a lot of research on the relationship between gut microbes and enteritis and bowel cancer, but most of them have focused on "what harmful microorganisms cause bowel cancer" and less on microbes that are beneficial to bowel cancerThe study by Nanjing Medical University filled some of the current gaps, from the mechanism level, to reveal the role of Akk bacteria and Amuc_1100, providing potential therapeutic targets for colitis and bowel cancer