高脂肪饮食而非肥胖可诱发肠道肿瘤

【报道】肥胖与高脂肪饮食一直以来被认为与肠胃患癌有关，但是其刺激肿瘤生长的原理却一直不明。Melek Arkan等人通过小鼠研究发现，高脂肪饮食本身就能刺激肠道肿瘤的生长。这篇文章刊登在2014年8月31日的《自然》在线期刊上。

中文翻译

【题目】高脂饮食造成的肠道菌群失调可促发小肠癌变并且这种癌变与肥胖无关

【译文】肥胖、运动量少等常见的西式生活特征是胃肠道癌症的危险因素。大量证据提示饮食可显著影响肠道细菌生态组成。再者,已有明确的证据证实菌群生态失调与癌症的发生发展有关。然而,高脂饮食引起的肠道菌群生态变化、进而影响肠道肿瘤发生的机制还需进一步证实。本研究我们证实高脂饮食能促发K- rasG12Dint肿瘤易感小鼠小肠肿瘤的发生,并与肥胖因素无关。高脂饮食结合K-ras 基因突变导致肠道菌群结构的改变，这种菌群改变与潘氏细胞介导的机体抗菌防御能力下降有关,其机制是降低肠道相关淋巴组织中树突状细胞的召集和MHCII分子提呈。以丁酸盐对高脂饮食K-rasG12Dint 小鼠进行治疗后，其肠道相关淋巴组织中树突状细胞召集正常化, 肿瘤的发展进程减弱。重要的一点是：MYD88基因缺失能阻断肿瘤的发生, 该基因是模式受体及Toll样受体的信号识别分子。把高脂饮食喂养的发生小肠肿瘤的小鼠粪便置入没有给予高脂饮食的健康成年K-rasG12Dint小鼠肠道内足以诱发肿瘤的发生。此外，用抗生素治疗可以完全阻断高脂饮食诱导的肿瘤发生, 这表示肠道菌群生态的明显改变在肿瘤发生过程中起重要的作用。综上，这些数据证实了机体和环境因素间的相互作用,通过选择菌群生态促发癌症的发生，同时提示遗传性肿瘤易感也是可以转化的.

英文原稿

[Title] High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity

[Author] Manon D. Schulz, Çiğdem Atay, Jessica Heringer, Franziska K. Romrig, Sarah Schwitalla, Begüm Aydin, Paul K. 

Ziegler, Julia Varga, Wolfgang Reindl, Claudia Pommerenke, Gabriela Salinas-Riester, Andreas Böck, Carl Alpert, Michael 

Blaut, Sara C. Polson, Lydia Brandl, Thomas Kirchner, Florian R. Greten, Shawn W. Polson & Melek C. Arkan

[Abstract] Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known 

risk factors for gastrointestinal cancers1. There is substantial evidence suggesting that diet markedly affects the composition 

of the intestinal microbiota2. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development3. 

However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity 

of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in 

the small intestine of genetically susceptible, K-rasG12Dint, mice independently of obesity. HFD consumption, in 

conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated 

with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC 

class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed 

K-rasG12Dint mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour 

progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors 

and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal 

tumours to healthy adult K-rasG12Dint mice was sufficient to transmit disease in the absence of an HFD. Furthermore, 

treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the 

microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal 

interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest 

that tumorigenesis is transmissible among genetically predisposed individuals.

原文地址: http://news.bioon.com/article/6658138.html