Modelling the role of microbial p-cresol in colorectal genotoxicity.
Modelling the role of microbial p-cresol in colorectal genotoxicity.
复制标题
DOI：
10.1080/19490976.2018.1534514
复制
发表时间：
2019
期刊：
影响因子：
12.2
通讯作者：
Commane DM
中科院分区：
文献类型：
--
作者：
Al Hinai EA;Kullamethee P;Rowland IR;Swann J;Walton GE;Commane DM
背景：需要更好地理解解释结直肠癌中饮食和肠道微生物群之间相互作用的机制。结肠中存在的遗传毒性微生物代谢物可能与致癌作用有关，并可能受到饮食的影响。目的：我们假设微生物对甲酚是一种结肠遗传毒素，并着手模拟结肠中的潜在暴露以及这些暴露对结肠细胞的影响。研究方法：使用人粪便发酵的分批培养物来确定响应于各种底物的对甲酚和其他代谢物的合成。评价发酵上清液的遗传毒性，并在体外研究对甲酚对结肠细胞的独立影响。结果如下：在分批发酵中，补充蛋白质增加酚类、吲哚类和对甲酚的合成，而补充低聚果糖（FOS）增加短链脂肪酸的合成。对甲酚是发酵上清液中对结肠细胞遗传毒性的最大预测因子。用外源性对甲酚加标发酵上清液进一步增加DNA损伤，并且对甲酚以剂量依赖性方式独立地诱导对HT 29和Caco-2细胞的DNA损伤，并影响细胞周期动力学。结论：在结肠中，对甲酚可能达到生理上显著的浓度，导致肠腔中的遗传毒性暴露，对甲酚的产生可能被底物减弱，因此饮食使其成为结肠中遗传毒性的潜在可改变生物标志物。
Background: A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet. Aims: We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells. Methods: Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro. Results: In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics. Conclusions: In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon.
登录
查看更多内容
影响因子：
4.4
作者：
Beaumont, Martin;Andriamihaja, Mireille;Lan, Annaig
通讯作者：
Lan, Annaig
DOI：
10.2215/cjn.12491211
发表时间：
2012-06-01
影响因子：
9.8
作者：
Patel, Kajal P.;Luo, Frank J. -G.;Meyer, Timothy W.
通讯作者：
Meyer, Timothy W.
影响因子：
4.7
作者：
Nistal E;Fernández-Fernández N;Vivas S;Olcoz JL
通讯作者：
Olcoz JL
影响因子：
1.8
作者：
Zhao, Guohua;Nyman, Margareta;Jonsson, Jan Ake
通讯作者：
Jonsson, Jan Ake
影响因子：
2.9
作者：
King, Roger A.;May, Bruce L.;Bird, Anthony R.
通讯作者：
Bird, Anthony R.