Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of laboratory medicine, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China.
Gut. 2020 Nov;69(11):1988-1997. doi: 10.1136/gutjnl-2019-320105. Epub 2020 Mar 13.
Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). () 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 engages the immune response in CAC.
Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised 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 or Amuc_1100 on the immune response in acute colitis and CAC were investigated.
was significantly reduced in patients with IBD and mice with colitis or CAC. 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, 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.
These data indicate that pasteurised or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.
肠道微生物群与炎症性肠病（IBD）和结直肠癌（CRC）有关。脆弱拟杆菌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，但它在减轻结肠炎相关结直肠癌（CAC）中的因果作用和分子机制仍不清楚。本研究探讨了脆弱拟杆菌如何参与 CAC 的免疫反应。
给小鼠用葡聚糖硫酸钠诱导结肠炎，然后用氧化偶氮甲烷建立 CAC，同时用巴氏消毒脆弱拟杆菌或特定外膜蛋白（Amuc_1100）处理。收集来自患有 IBD 或 CRC 的小鼠和患者的粪便进行 16S rRNA 测序。研究了脆弱拟杆菌或 Amuc_1100 对急性结肠炎和 CAC 中免疫反应的影响。
脆弱拟杆菌在 IBD 患者和结肠炎或 CAC 小鼠中显著减少。脆弱拟杆菌或 Amuc_1100 可改善结肠炎，减少结肠中浸润的巨噬细胞和 CD8 细胞毒性 T 淋巴细胞（CTL）。它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 提高了脾脏中的 PD-1 CTL。此外，脆弱拟杆菌和 Amuc_1100 通过在结肠和 MLN 中扩增 CTL 来减轻肿瘤发生。值得注意的是，它们通过 TNF-α诱导和 PD-1 下调激活了 MLN 中的 CTL。Amuc_1100 可以刺激和激活 CT26 细胞条件培养基中脾细胞中的 CTL。
这些数据表明巴氏消毒脆弱拟杆菌或 Amuc_1100 可以通过调节 CTL 来减轻结肠炎和 CAC。
