Nugent Julia L, McCoy Amber N, Addamo Cassandra J, Jia Wei, Sandler Robert S, Keku Temitope O
School of Medicine, University of North Carolina at Chapel Hill , 321 South Columbia Street, Chapel Hill, North Carolina 27599, United States.
J Proteome Res. 2014 Apr 4;13(4):1921-9. doi: 10.1021/pr4009783. Epub 2014 Mar 21.
Several studies have linked bacterial dysbiosis with elevated risk of colorectal adenomas and cancer. However, the functional implications of gut dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the "metabolome", which may contribute to the development of neoplasia in the large bowel. We assessed the metabolome in normal rectal mucosal biopsies of 15 subjects with colorectal adenomas and 15 nonadenoma controls by liquid chromatography and gas chromatography time-of-flight mass spectrometry. Quantitative real-time PCR was used to measure abundances of specific bacterial taxa. We identified a total of 274 metabolites. Discriminant analysis suggested a separation of metabolomic profiles between adenoma cases and nonadenoma controls. Twenty-three metabolites contributed to the separation, notably an increase in adenoma cases of the inflammatory metabolite prostaglandin E2 and a decrease in antioxidant-related metabolites 5-oxoproline and diketogulonic acid. Pathway analysis suggested that differential metabolites were significantly related to cancer, inflammatory response, carbohydrate metabolism, and GI disease pathways. Abundances of six bacterial taxa assayed were increased in cases. The 23 differential metabolites demonstrated correlations with bacteria that were different between cases and controls. These findings suggest that metabolic products of bacteria may be responsible for the development of colorectal adenomas and CRC.
多项研究已将肠道菌群失调与结直肠腺瘤及癌症风险升高联系起来。然而，肠道菌群失调的功能影响仍不明确。肠道细菌有助于营养物质代谢，并产生被称为“代谢组”的小分子，这些小分子可能促进大肠肿瘤的发生。我们通过液相色谱和气相色谱飞行时间质谱法评估了15名患有结直肠腺瘤的受试者和15名非腺瘤对照者的正常直肠黏膜活检组织中的代谢组。采用定量实时PCR测定特定细菌类群的丰度。我们共鉴定出274种代谢物。判别分析表明腺瘤病例和非腺瘤对照者的代谢组学特征存在分离。23种代谢物促成了这种分离，特别是腺瘤病例中炎症代谢物前列腺素E2增加，以及抗氧化相关代谢物5-氧脯氨酸和二酮古洛糖酸减少。通路分析表明差异代谢物与癌症、炎症反应、碳水化合物代谢和胃肠道疾病通路显著相关。所检测的6种细菌类群的丰度在病例中增加。这23种差异代谢物与病例和对照中不同的细菌存在相关性。这些发现表明细菌的代谢产物可能是结直肠腺瘤和结直肠癌发生的原因。
