High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
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DOI：
10.1038/nature13398
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发表时间：
2014-10-23
期刊：
影响因子：
64.8
通讯作者：
Arkan, Melek C.
中科院分区：
文献类型：
--
作者：
Schulz, Manon D.;Atay, Cigdem;Heringer, Jessica;Romrig, Franziska K.;Schwitalla, Sarah;Aydin, Begum;Ziegler, Paul K.;Varga, Julia;Reindl, Wolfgang;Pommerenke, Claudia;Salinas-Riester, Gabriela;Boeck, Andreas;Alpert, Carl;Blaut, Michael;Polson, Sara C.;Brandl, Lydia;Kirchner, Thomas;Greten, Florian R.;Polson, Shawn W.;Arkan, Melek C.
西方生活方式的几个共同点，包括肥胖和体力活动减少，是已知的胃肠道癌症风险。有大量证据表明，饮食深刻影响肠道微生物群的组成。此外，现在有明确的证据将生态失调与癌症发展联系起来。然而，高脂饮食（HFD）介导的微生物群落变化影响肠道肿瘤发生严重程度的机制仍有待确定。在这里，我们证明，HFD促进肿瘤的发展，在遗传易感的K-rasG 12 Dint小鼠的小肠独立的肥胖。HFD消耗与K-Ras突变一起介导肠道微生物群组成的转变，这与潘氏细胞抗微生物宿主防御的减少有关，这损害了树突状细胞（DC）募集和肠道相关淋巴组织（GALT）中的MHC-II呈递。当K-rasG 12 Dint小鼠补充丁酸盐时，GALT中的DC募集可以正常化，并且肿瘤进展减弱。重要的是，Myd 88缺陷阻断肿瘤进展。在不存在HFD的情况下，将患病供体的粪便样本转移到健康成年K-rasG 12 Dint小鼠中足以传播疾病。此外，抗生素治疗完全阻断了HFD诱导的肿瘤进展，这表明不同的微生物转移在加重疾病中起着关键作用。总的来说，这些数据强调了宿主和环境因素之间的相互作用在选择有利于致癌的微生物群中的重要性，并表明肿瘤可能在遗传易感个体中传播。
Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is substantial evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development. Yet the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that HFD promotes tumor progression in the small intestine of genetically susceptible K-rasG12Dint mice independently of obesity. HFD consumption in conjunction with K-Ras mutation mediates a shift in the composition of gut microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHC-II presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized, and tumor progression attenuated, when K-rasG12Dint mice are supplemented with butyrate. Importantly, Myd88-deficiency blocks tumor progression. Transfer of fecal samples from diseased donors into healthy adult K-rasG12Dint mice is sufficient to transmit disease in the absence of HFD. Furthermore, treatment with antibiotics completely blocks HFD-induced tumor progression suggesting a pivotal role for distinct microbial shifts in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting microbiota that favor carcinogenesis, and suggest tumorigenesis may be transmissible among genetically predisposed individuals.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
微生物组和癌症。
DOI：
10.1038/nrc3610
发表时间：
2013-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
先天和适应性免疫会灵活合作，以维持宿主 - 微生物互助。
DOI：
10.1126/science.1172747
发表时间：
2009-07-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Slack E;Hapfelmeier S;Stecher B;Velykoredko Y;Stoel M;Lawson MA;Geuking MB;Beutler B;Tedder TF;Hardt WD;Bercik P;Verdu EF;McCoy KD;Macpherson AJ
通讯作者：
Macpherson AJ