AbstractAs a Gram‐negative anaerobic bacterium, Akkermansia muciniphila (AKK) participates in the immune response in many cancers. Our study focused on the factors and molecular mechanisms of AKK affecting immune escape in lung adenocarcinoma (LUAD). We cultured AKK bacteria, prepared AKK outer membrane protein Amuc_1100 and constructed a subcutaneous graft tumour mouse model. A549, NCI‐H1395 cells and mice were respectively treated with inactivated AKK, Amuc_1100, Ruxolitinib (JAK inhibitor) and RO8191 (JAK activator). CD8+ T cells that penetrated the membrane were counted in the Transwell assay. The toxicity of CD8+ T cells was evaluated by lactate dehydrogenase assay. Western blot was applied to determine JAK/STAT‐related protein and PD‐L1 expression, whilst CCL5, granzyme B and INF‐γ expression were assessed through enzyme‐linked immunosorbent assay (ELISA). The proportion of tumour‐infiltrating CD8+ T cells and the levels of granzyme B and INF‐γ were determined by flow cytometry. AKK markedly accelerated A549 and NCI‐H1395 recruiting CD8+ T cells and enhanced CD8+ T cell toxicity. Amuc_1100 purified from AKK exerted the same promoting effects. Besides, Amuc_1100 dramatically suppressed PD‐L1, p‐STAT and p‐JAK expression and enhanced CCL5, granzyme B and INF‐γ expression. Treatment with Ruxolitinib accelerated A549 and NCI‐H1395 cells recruiting CD8+ T cells, enhanced CD8+ T cell toxicity, CCL5, granzyme B and INF‐γ expression, and inhibited PD‐L1 expression. In contrast, the RO8191 treatment slowed down the changes induced by Amuc_1100. Animal experiments showed that Amuc_1100 was found to increase the number of tumour‐infiltrating CD8+ T cells, increase the levels of granzyme B and INF‐γ and significantly inhibit the expression of PD‐L1, p‐STAT and p‐JAK, which exerted an antitumour effect in vivo. In conclusion, through inhibiting the JAK/STAT signalling pathway, AKK outer membrane protein facilitated the recruitment of CD8+ T cells in LUAD and suppressed the immune escape of cells.

2023-12-01·Biochemical and Biophysical Research Communications

Akkermansia muciniphila and its outer membrane protein Amuc_1100 prevent high-fat diet-induced nonalcoholic fatty liver disease in mice

Article

作者: Zhang, Min ; Liu, Xingyu ; Zhou, Wei ; Zhu, Haiyan ; Cui, Yanan ; Chen, Mengyun ; Qu, Danni

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. A. muciniphila and its outer membrane protein Amuc_1100 ameliorate metabolic disorders, enteritis, depression, and other diseases in mice. The NAFLD mouse model was established by feeding a high-fat diet (HFD) for 10 weeks. To assess the effect of A. muciniphila and Amuc_1100 on NAFLD, we used atorvastatin, a common lipid-lowering drug, as a positive control. A. muciniphila and Amuc_1100 significantly reduced body weight and serum ALT and AST levels, and improved serum lipid levels in NAFLD mice, which had similar effects to Ator. In addition, A. muciniphila and Amuc_1100 decreased the concentration of LPS in the serum and upregulated the mRNA expression of the colonic tight junction proteins. In the liver, A. muciniphila and Amuc_1100 significantly reduced the mRNA expression levels of nodular receptor protein 3 (NLRP3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB), and the protein and mRNA expression levels inflammatory cytokines. At the genus level, Amuc_1100 treatment significantly reduced the abundance of Coriobacteriaceae_UCG-002 produced by the HFD. The abundances of Blautia, norank_f__Ruminococcaceae, Lachnoclostridium, GCA-900066575 and Lachnospiraceae_UCG-006 increased dramatically. Together, A. muciniphila and Amuc_1100 alleviate HFD-induced NAFLD by acting on the gut-liver axis and regulating gut microbes.

2023-01-01·Physiology & Behavior

Outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates antibiotic-induced anxiety and depression-like behavior in mice

Article

作者: Zhang, Min ; Sun, Yan ; Zhu, Haiyan ; Cheng, Rongrong ; Tang, Zhengquan

Akkermansia muciniphila is present in the mucus layer of its host gut, and its outer membrane protein Amuc_1100 has a significant ameliorative effect on metabolic disorders and emotional memory aspects of enteritis, obesity, depression, and anxiety in the host. Antibiotics affect gut microbial composition, leading to imbalance and behavioral changes in the gut-brain axis, while probiotics have a protective effect against behavioral changes caused by gut flora disorders. In the present study, a depressed mouse model using a broad-spectrum cocktail mixture resulted in increased anxiety and depression-like behavior, decreased serum and hippocampal levels of 5-hydroxytryptamine (5-HT), and increased serum corticosterone (cort) levels. After application of A. muciniphila and Amuc_1100, anxiety and depression-like behavior in antibiotic-treated mice were significantly alleviated. In addition, the brain derived neurotrophic factor / Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway was altered, glial fibrillary acidic protein (GFAP) expression increased, and c-Fos protein expression decreased in the hippocampus of antibiotic-treated mice. After treatment with A. muciniphila and Amuc_1100, BDNF and TrkB levels were restored in the hippocampus and cortex. These results suggest that A. muciniphila and Amuc_1100 may alleviate antibiotic-induced anxiety and depression by affecting the BDNF/TrkB signaling pathway.

100 项与 Amuc_1100 相关的药物交易

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