仁济医院:二甲双胍抗大肠癌的新机制
创作:aluba 审核:aluba 2020年10月19日
  • 对比42名结直肠癌患者及51名健康对照的粪便菌群,鉴定出多个结直肠癌相关菌属;
  • 总结18项研究,鉴定出二甲双胍处理导致的131个菌属变化,包括5个与结直肠癌相关的菌属:拟杆菌属、链球菌属、无色杆菌属、Alistipes菌属及梭杆菌属;
  • 在体外,二甲双胍可抑制具核梭杆菌的生长;
  • 在APCmin/+小鼠中,二甲双胍处理可抑制结直肠肿瘤形成及具核梭杆菌诱导的结直肠肿瘤增加;
  • 二甲双胍对结直肠肿瘤的抑制作用与其对Alistipes等菌属的影响相关。
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二甲双胍可调节肠道菌群。来自上海交通大学医学院附属仁济医院的熊华团队与房静远团队在EBioMedicine上发表的一项最新研究,发现在体外,二甲双胍可抑制具核梭杆菌的生长;而在结直肠癌小鼠模型中,二甲双胍可调控结直肠癌相关菌属的相对丰度,并抑制具核梭杆菌诱导的结直肠肿瘤形成。
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EBioMedicine [IF:11.205]

Metformin elicits antitumour effect by modulation of the gut microbiota and rescues Fusobacterium nucleatum-induced colorectal tumourigenesis

二甲双胍通过调节肠道菌群并逆转具核梭杆菌诱导的结直肠肿瘤发生以发挥抗肿瘤作用

10.1016/j.ebiom.2020.103037

2020-10-09, Article

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Background: The effect of metformin on gut microbiota has been reported, but whether metformin can suppress colorectal cancer (CRC) by affecting gut microbiota composition and rescue F. nucleatum-induced tumourigenicity remains unclear.
Methods: To identify microbiota associated with both CRC occurrence and metformin treatment, first, we reanalyzed the gut microbiome of our previous data on two human cohorts of normal and CRC individuals. Subsequently, we summarized microbiota altered by metformin from published literatures. Several taxa, including Fusobacterium, were associated with both CRC occurrence and metformin treatment. We investigated the effect of metformin on APCMin/+ mice given with or without F. nucleatum. 16S rRNA gene sequencing was performed.
Findings: We summarized 131 genera altered by metformin from 18 published literatures. Five genera reported to be changed by metformin, including Bacteroides, Streptococcus, Achromobacter, Alistipes and Fusobacterium, were associated with CRC in both of our human cohorts. Metformin relieved the symptoms caused by F. nucleatum administration in APCMin/+ mice, and showed promise in suppressing intestinal tumour formation and rescuing F. nucleatum-induced tumourigenicity. Administration of F. nucleatum and/or metformin had effect on gut microbiome structure, composition and functions of APCMin/+ mice.
Interpretation: This study pioneers in predicting critical CRC-associated taxa contributing to the antitumour effect of metformin, and correlating gut microbiome with the antitumour effect of metformin in experimental animals. We presented a basis for future investigations into metformin's potential effect on suppressing F. nucleatum-induced tumor formation in vivo.

First Authors:
Xiaowen Huang,Xialu Hong

Correspondence Authors:
Jingyuan Fang,Hua Xiong

All Authors:
Xiaowen Huang,Xialu Hong,Jilin Wang,Tiantian Sun,TaChung Yu,Yanan Yu,Jingyuan Fang,Hua Xiong

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