Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.
Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.
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光/暗转变促进酒精诱导的结肠癌发生：肠道炎症环境和微生物群的可能作用。
DOI：
10.3390/ijms17122017
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发表时间：
2016-12-02
影响因子：
5.6
通讯作者：
Keshavarzian A
中科院分区：
文献类型：
--
作者：
Bishehsari F;Saadalla A;Khazaie K;Engen PA;Voigt RM;Shetuni BB;Forsyth C;Shaikh M;Vitaterna MH;Turek F;Keshavarzian A
背景：结直肠癌（CRC）与现代生活方式有关。长期饮酒-现代社会大多数人的常见习惯-增加了CRC的风险。我们的研究小组表明，长期饮酒会增加小鼠CRC模型中的息肉病。在此，我们评估昼夜节律紊乱（另一种现代生活方式习惯）在促进酒精相关CRC中的作用。方法：TS 4Cre ×腺瘤性结肠息肉病（APC）lox 468小鼠接受（a）含酒精饮食，同时维持正常的12 h光照：12 h黑暗周期;或（B）含酒精饮食联合每周一次12 h光照：黑暗（LD）周期相位逆转的昼夜节律破坏。在八周的完全酒精和/或LD转换后处死小鼠以收集肠样品。比较动物组之间的肿瘤数量、大小和组织学分级。分析并比较肥大细胞蛋白酶2（MCP 2）和6（MCP 6）组织学评分。在基线和四周实验操作后收集的粪便用于微生物群分析。结果如下：酒精和LD转移的结合加速了肠息肉病，息肉大小显著增加，并导致晚期肿瘤形成。与基质类胰蛋白酶阳性肥大细胞在结肠癌发生中的致病作用一致，mMCP 6（基质）/mMCP 2（上皮内）肥大细胞的比例在LD移位后增加。各组之间的基线微生物群相似，实验操作导致各组之间的微生物群组成存在显著差异。结论：昼夜节律被光暗转换破坏会加重酒精诱导的息肉病和结直肠癌。昼夜节律破坏的作用可以至少部分地通过经由微生物群的变化促进促肿瘤发生的炎性环境来介导。
Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.
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DOI：
10.4161/cc.9.6.11046
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gery S;Koeffler HP
通讯作者：
Koeffler HP
影响因子：
10.5
作者：
Brennan CA;Garrett WS
通讯作者：
Garrett WS
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.2
作者：
Mariat D;Firmesse O;Levenez F;Guimarăes V;Sokol H;Doré J;Corthier G;Furet JP
通讯作者：
Furet JP
影响因子：
--
作者：
Chen X;Churchill MJ;Nagar KK;Tailor YH;Chu T;Rush BS;Jiang Z;Wang EB;Renz BW;Wang H;Fung MC;Worthley DL;Mukherjee S;Wang TC
通讯作者：
Wang TC