天津总医院:肠道菌群失调引发大肠癌
  • 健康对照和结直肠癌(CRC)患者的粪便灌胃抗生素处理的Apcmin/+ 小鼠,分析肠道组织炎症状态、差异基因表达和肠道菌群及代谢;
  • CRC患者肠道菌群促进小鼠肠道肿瘤形成,促进癌细胞增殖,抑制癌细胞凋亡;
  • CRC患者肠道菌群破坏小鼠肠道物理、化学和免疫屏障,诱发慢性炎症;
  • 粪菌移植后,肠道肿瘤组织基因表达谱发生改变,参与肿瘤形成的Wnt信号通路被激活;
  • 粪便中致病菌丰度增加,产短链脂肪酸(SCFA)的细菌丰度减少,SCFA含量减少。
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越来越多的证据表明肠道菌群失调与结直肠癌(CRC)之间存在密切关系,90%以上的CRC由腺瘤发展而来。天津总医院的曹海龙、姜葵和王邦茂与团队近期发表在EBioMedicine杂志的一项研究,探讨了肠道菌群失调在肠腺瘤发生发展中的重要作用。该研究对抗生素处理之后的Apcmin/+ 小鼠进行CRC患者或健康对照的粪菌移植,发现CRC患者肠道菌群可破坏小鼠肠道物理、化学和免疫屏障,诱发慢性炎症,促进小鼠肠道肿瘤形成。其机制在于肠道菌群可改变肠道组织基因表达谱,激活参与肿瘤形成的Wnt信号通路。该研究提出了一种肠道微生物群对抗CRC的新策略,为未来的临床治疗策略提供理论依据。
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EBioMedicine [IF:6.68]

Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice

结直肠癌患者肠道菌群可促进Apcmin/+小鼠肠腺瘤的进展

10.1016/j.ebiom.2019.09.021

2019-10-05, Article

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Background: 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.
Methods: The Apcmin/+ 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.
Findings: The Apcmin/+mice 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.
Interpretation: 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 Apcmin/+mice, 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.

First Authors:
Lu Li,Xiaofei Li,Weilong Zhong

Correspondence Authors:
Bangmao Wang,Kui Jiang,Hailong Cao

All Authors:
Lu Li,Xiaofei Li,Weilong Zhong,Min Yang,Mengque Xu,Yue Sun,Jiaheng Ma,Tianyu Liu,Xueli Song,Wenxiao Dong,Xiang Liu,Yange Chen,Yi Liu,Zaripa Abla,Wentian Liu,Bangmao Wang,Kui Jiang,Hailong Cao

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EBioMedicine期刊

Faecal microbiota transplantation, a promising way to treat colorectal cancer

Yanru Ma, Haoyan Chen,2019-10-21

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