某种肠道细菌
粪便
生物
肠道菌群
结直肠癌
癌变
促炎细胞因子
偶氮甲烷
微生物群
阿克曼西亚
转录组
免疫学
内科学
癌症研究
内分泌学
拟杆菌
癌症
医学
微生物学
生物信息学
炎症
基因表达
遗传学
细菌
基因
作者
Xing Kang,Siu-Kin Ng,Changan Liu,Yufeng Lin,Yunfei Zhou,Thomas Kwong,Yun‐Bi Ni,Thomas Y. Lam,William Ka Kei Wu,Hong Wei,Joseph J.Y. Sung,Jun Yu,Sunny Hei Wong
出处
期刊:EBioMedicine
[Elsevier]
日期:2023-07-01
卷期号:93: 104670-104670
被引量:2
标识
DOI:10.1016/j.ebiom.2023.104670
摘要
BackgroundObesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown.MethodsAzoxymethane (AOM)-treated, ApcMin/+ and germ-free mice were gavaged with feces from obese individuals and control subjects respectively. The colonic tumor load and number were recorded at the endpoint in two carcinogenic models. The gut microbiota composition and colonic transcriptome were assessed by metagenomic sequencing and RNA sequencing, respectively. The anticancer effects of bacteria depleted in fecal samples of obese individuals were validated.FindingsConventional AOM-treated and ApcMin/+ mice receiving feces from obese individuals showed significantly increased colon tumor formation compared with those receiving feces from control subjects. AOM-treated mice receiving feces from obese individuals showed impaired intestinal barrier function and significant upregulation of pro-inflammatory cytokines and activation of oncogenic Wnt signaling pathway. Consistently, transferring feces from obese individuals to germ-free mice led to increased colonic cell proliferation, intestinal barrier function impairment, and induction of oncogenic and proinflammatory gene expression. Moreover, germ-free mice transplanted with feces from obese human donors had increased abundance of potential pathobiont Alistipes finegoldii, and reduced abundance of commensals Bacteroides vulgatus and Akkermansia muciniphila compared with those receiving feces from human donors with normal body mass index (BMI). Validation experiments showed that B. vulgatus and A. muciniphila demonstrated anti-proliferative effects in CRC, while A. finegoldii promoted CRC tumor growth.InterpretationOur results supported the role of obesity-associated microbiota in colorectal carcinogenesis and identified putative bacterial candidates that may mediate its mechanisms. Microbiota modulation in obese individuals may provide new approaches to prevent or treat obesity-related cancers including CRC.FundingThis work was funded by National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203), National Natural Science Foundation of China (81922082), RGC Theme-based Research Scheme Hong Kong (T21-705/20-N), RGC Research Impact Fund Hong Kong (R4632-21F), RGC-CRF Hong Kong (C4039-19GF and C7065-18GF), RGC-GRF Hong Kong (14110819, 14111621), and NTU Start-Up Grant (021337-00001).
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