Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado, United States of America.
PLoS One. 2013 Aug 6;8(8):e70803. doi: 10.1371/journal.pone.0070803. Print 2013.
In this study we used stool profiling to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to identify how microbial functions may influence CRC development. Stool samples were collected from healthy adults (n = 10) and colorectal cancer patients (n = 11) prior to colon resection surgery at the University of Colorado Health-Poudre Valley Hospital in Fort Collins, CO. The V4 region of the 16s rRNA gene was pyrosequenced and both short chain fatty acids and global stool metabolites were extracted and analyzed utilizing Gas Chromatography-Mass Spectrometry (GC-MS). There were no significant differences in the overall microbial community structure associated with the disease state, but several bacterial genera, particularly butyrate-producing species, were under-represented in the CRC samples, while a mucin-degrading species, Akkermansia muciniphila, was about 4-fold higher in CRC (p<0.01). Proportionately higher amounts of butyrate were seen in stool of healthy individuals while relative concentrations of acetate were higher in stools of CRC patients. GC-MS profiling revealed higher concentrations of amino acids in stool samples from CRC patients and higher poly and monounsaturated fatty acids and ursodeoxycholic acid, a conjugated bile acid in stool samples from healthy adults (p<0.01). Correlative analysis between the combined datasets revealed some potential relationships between stool metabolites and certain bacterial species. These associations could provide insight into microbial functions occurring in a cancer environment and will help direct future mechanistic studies. Using integrated "omics" approaches may prove a useful tool in identifying functional groups of gastrointestinal bacteria and their associated metabolites as novel therapeutic and chemopreventive targets.
在这项研究中，我们使用粪便分析来鉴定在结直肠癌（CRC）患者和健康对照者之间存在差异的肠道细菌和代谢产物，以确定微生物功能如何影响 CRC 的发展。在科罗拉多大学健康-普韦布洛谷医院（科罗拉多州柯林斯堡）进行结肠切除术前，从健康成年人（n = 10）和结直肠癌患者（n = 11）中收集粪便样本。使用焦磷酸测序对 16s rRNA 基因的 V4 区进行测序，并用气相色谱-质谱联用（GC-MS）提取和分析短链脂肪酸和全球粪便代谢物。与疾病状态相关的总体微生物群落结构没有显着差异，但几种细菌属，特别是产生丁酸盐的物种，在 CRC 样本中代表性较低，而阿克曼氏菌属（Akkermansia muciniphila）等粘液降解物种在 CRC 中约高 4 倍（p <0.01）。健康个体的粪便中丁酸盐含量较高，而 CRC 患者的粪便中乙酸盐浓度相对较高。GC-MS 分析显示 CRC 患者的粪便样本中氨基酸浓度较高，而健康成年人的粪便样本中多不饱和脂肪酸和单不饱和脂肪酸以及熊去氧胆酸（一种结合胆汁酸）浓度较高（p <0.01）。综合数据集的相关分析显示粪便代谢物与某些细菌之间存在一些潜在关系。这些关联可以深入了解癌症环境中发生的微生物功能，并有助于指导未来的机制研究。使用集成的“组学”方法可能是鉴定胃肠道细菌及其相关代谢物的功能组作为新型治疗和化学预防靶点的有用工具。
