Objective Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Akkermansia muciniphila (A. muciniphila) is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how A. muciniphila engages the immune response in CAC. Design Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised A. muciniphila or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of A. muciniphila or Amuc_1100 on the immune response in acute colitis and CAC were investigated. Results A. muciniphila was significantly reduced in patients with IBD and mice with colitis or CAC. A. muciniphila or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8+ cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32+ macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1+ CTLs in the spleen. Moreover, A. muciniphila and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium. Conclusions These data indicate that pasteurised A. muciniphila or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.

中文翻译：

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来自 Akkermansia muciniphila 或巴氏杀菌细菌的纯化膜蛋白通过调节小鼠的 CD8+T 细胞来减弱结肠炎相关的肿瘤发生

目的肠道微生物群与炎症性肠病（IBD）和结直肠癌（CRC）有关。Akkermansia muciniphila (A. muciniphila) 是一种革兰氏阴性厌氧菌，在 IBD 患者的粪便微生物群中选择性减少，但其在钝性结肠炎相关结直肠癌 (CAC) 中的致病作用和分子机制仍无定论。这项研究调查了 A. muciniphila 如何参与 CAC 中的免疫反应。设计小鼠给予葡聚糖硫酸钠诱导结肠炎，然后给予氧化偶氮甲烷以建立 CAC，有或没有巴氏杀菌 A. muciniphila 或特定的外膜蛋白 (Amuc_1100) 治疗。收集小鼠和 IBD 或 CRC 患者的粪便进行 16S rRNA 测序。A. 的影响 研究了 muciniphila 或 Amuc_1100 对急性结肠炎和 CAC 免疫反应的影响。结果 A. muciniphila 在 IBD 患者和结肠炎或 CAC 小鼠中显着减少。A. muciniphila 或 Amuc_1100 可以改善结肠炎，减少结肠中浸润的巨噬细胞和 CD8+ 细胞毒性 T 淋巴细胞 (CTL)。他们的治疗还减少了结肠炎小鼠脾脏和肠系膜淋巴结 (MLN) 中的 CD16/32+ 巨噬细胞。Amuc_1100 升高脾脏中的 PD-1+ CTL。此外，A. muciniphila 和 Amuc_1100 通过扩大结肠和 MLN 中的 CTL 来抑制肿瘤发生。值得注意的是，它们激活了 MLN 中的 CTL，如 TNF-α 诱导和 PD-1 下调所示。Amuc_1100 可以刺激和激活 CT26 细胞条件培养基中脾细胞的 CTL。结论 这些数据表明巴氏杀菌的 A.