背景:结直肠癌(CRC)是一种公共卫生问题,也是全球第二大常见疾病。这是由于遗传编码,并受到环境因素的影响,其中肠道微生物群起着重要作用。这项研究的目的是比较CRC患者与健康对照的微生物群组成,并鉴定CRC患者中上调和下调的蛋白质和代谢物。使用下一代测序方法,香港BGIDNBSEQ-T7分析了五名女性(4名CRC患者和一名健康对照)的粪便样本,中国。此外,使用LC-MS/MS技术进行蛋白质组学和代谢组学分析。
结果:已在CRC患者中观察到肠道菌群失衡,与健康对照相比,所有分类水平的微生物群多样性增加。Where,在功能水平上,细菌物种参与许多不同的途径,其中从头核苷酸合成和氨基酸途径在CRC患者中异常上调。CRC患者的蛋白质组学和代谢组学图谱显示不同的蛋白质和代谢产物,总共有360和158种蛋白质和代谢物,与健康对照组相比,分别高表达,倍数变化≥1.2。其中高表达的蛋白质是转酮醇酶,含寿司结构域的蛋白质,硫化物醌氧化还原酶蛋白,AAA家族ATP酶蛋白,碳酸酐酶,IgGFc结合蛋白,核苷二磷酸激酶蛋白,芳基硫酸酯酶,碱性磷酸酶蛋白,磷酸甘油酸激酶,含蛋白激酶结构域的蛋白质,非特异性丝氨酸/苏氨酸蛋白激酶,酰基辅酶A合成酶和含EF手结构域的蛋白质。一些不同的代谢物,牛磺酸,牛磺胆酸,7-酮脱氧胆酸,甘牛脱氧胆酸,甘胆酸,和牛磺鹅去氧胆酸属于胆汁酸代谢产物。
结论:一些细菌种类,蛋白质,和代谢物可作为CRC的诊断生物标志物。我们的研究为使用多组学技术解决肠道微生物群与CRC之间的关系提供了见解。
Colorectal cancer (CRC) is a public health concern and the second most common disease worldwide. This is due to genetic coding and is influenced by environmental aspects, in which the gut microbiota plays a significant role. The purpose of this
study was to compare the microbiota makeup of CRC patients with that of healthy control and to identify upregulated and downregulated proteins and metabolites in CRC patients. Using a next-generation sequencing approach, fecal samples of five females (4 CRC patients and one healthy control) were analyzed by BGI DNBSEQ-T7, Hong Kong, China. Furthermore, proteomics and metabolomics analysis were performed using LC-MS/MS technique.
Dysbiosis of gut microbiota has been observed in patients with CRC, with an increase in microbiota diversity at all taxonomic levels relative to healthy control. Where, at the functional level the bacterial species participate in many different pathways among them de novo nucleotide synthesis and amino acids pathways were aberrantly upregulated in CRC patients. Proteomics and metabolomics profiles of CRC patients showed different proteins and metabolites, a total of 360 and 158 proteins and metabolites, respectively were highly expressed compared to healthy control with fold change ≥ 1.2. Among the highly expressed proteins were transketolase, sushi domain-containing protein, sulfide quinone oxidoreductase protein, AAA family ATPase protein, carbonic anhydrase, IgG Fc-binding protein, nucleoside diphosphate kinase protein, arylsulfatase, alkaline phosphatase protein, phosphoglycerate kinase, protein kinase domain-containing protein, non-specific serine/threonine protein kinase, Acyl-CoA synthetase and EF-hand domain-containing protein. Some of the differential metabolites, Taurine, Taurocholic acid, 7-ketodeoxycholic acid, Glycochenodeoxycholic acid, Glycocholic acid, and Taurochenodeoxycholic acid that belong to bile acids metabolites.
Some bacterial species, proteins, and metabolites could be used as diagnostic biomarkers for CRC. Our
study paves an insight into using multi-omics technology to address the relationship between gut microbiota and CRC.