High-fat diet-induced dysbiosis mediates MCP-1/CCR2 axis-dependent M2 macrophage polarization and promotes intestinal adenoma-adenocarcinoma sequence
High-fat diet-induced dysbiosis mediates MCP-1/CCR2 axis-dependent M2 macrophage polarization and promotes intestinal adenoma-adenocarcinoma sequence
复制标题
高脂饮食引起的生态失调介导MCP-1/CCR2轴依赖性M2巨噬细胞极化并促进肠腺瘤-腺癌序列
DOI：
10.1111/jcmm.14984
复制
发表时间：
2020-01-19
影响因子：
5.3
通讯作者：
Cao, Hailong
中科院分区：
文献类型：
--
作者：
Liu, Tianyu;Guo, Zixuan;Cao, Hailong
High-fat diet (HFD) is a well-known risk factor for gut microbiota dysbiosis and colorectal cancer (CRC). However, evidence relating HFD, gut microbiota and carcinogenesis is limited. Our study aimed to demonstrate that HFD-induced gut dysbiosis promoted intestinal adenoma-adenocarcinoma sequence. In clinical study, we found that HFD increased the incidence of advanced colorectal neoplasia (AN). The expression of monocyte chemoattractant protein 1 (MCP-1), CC chemokine receptor 2 (CCR2) and CD163 in CRC patients with HFD was significantly higher than that in CRC patients with normal diet. When it comes to the Apc(min/+) mice, HFD consumption could induce gut dysbiosis and promote intestinal carcinogenesis, accompanying with activation of MCP-1/CCR2 axis that recruited and polarized M2 tumour-associated macrophages. Interestingly, transfer of faecal microbiota from HFD-fed mice to another batch of Apc(min/+) mice in the absence of HFD could also enhance carcinogenesis without significant body weight gain and induced MCP-1/CCR2 axis activation. HFD-induced dysbiosis could also be transmitted. Meanwhile, antibiotics cocktail treatment was sufficient to inhibit HFD-induced carcinogenesis, indicating the vital role of dysbiosis in cancer development. Conclusively, these data indicated that HFD-induced dysbiosis accelerated intestinal adenoma-adenocarcinoma sequence through activation of MCP-1/CCR2 axis, which would provide new insight into better understanding of the mechanisms and prevention for HFD-related CRC.
