Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.
Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
EBioMedicine. 2019 Oct;48:301-315. doi: 10.1016/j.ebiom.2019.09.021. Epub 2019 Oct 5.
Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.
The Apc mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.
The Apcmice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.
Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmice, suggesting that a new strategy to target gut microbiota against CRC could be noted. FUND: The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.
越来越多的证据表明肠道菌群失调与结直肠癌（CRC）密切相关。由于>90%的 CRC 由腺瘤发展而来，我们旨在研究肠道微生物群落失衡在肠腺瘤进展中的关键作用。
用抗生素鸡尾酒处理 Apc 小鼠，然后用磷酸盐缓冲盐水（PBS）、健康对照者或 CRC 患者的粪便灌胃。分离肠组织进行组织病理学、western blot 和 RNA-seq 分析。通过 16S rDNA 扩增子测序和气相色谱分析粪便和短链脂肪酸（SCFA）的微生物群。
与用健康对照者粪便或 PBS 灌胃的 Apc 小鼠相比，用 CRC 患者粪便灌胃的 Apc 小鼠有更多的肠道肿瘤。CRC 患者粪便的给予增加了肿瘤细胞的增殖和减少了凋亡，同时损害了肠道屏障功能并上调了促炎细胞因子谱。β-连环蛋白和细胞周期蛋白 D1 的表达上调进一步表明 Wnt 信号通路的激活。FMT 后致病性细菌的丰度增加，而产生 SCFA 的细菌和 SCFA 的产生减少。
CRC 患者的肠道微生物群破坏了肠道屏障，诱导了低度炎症和菌群失调。改变的肠道微生物群增强了 Apc 小鼠肠腺瘤的进展，表明针对 CRC 靶向肠道微生物群的新策略值得注意。
本研究得到了国家自然科学基金、天津市应用基础与前沿技术研究计划和中国博士后科学基金的支持。
