Integrated microbiome and metabolome analysis reveals a novel interplay between commensal bacteria and metabolites in colorectal cancer
Integrated microbiome and metabolome analysis reveals a novel interplay between commensal bacteria and metabolites in colorectal cancer
复制标题
综合微生物组和代谢组分析揭示了结直肠癌中共生细菌和代谢物之间的新相互作用
DOI：
10.7150/thno.35186
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Ma, Yanlei
中科院分区：
文献类型：
--
作者：
Yang, Yongzhi;Misra, Biswapriya B.;Ma, Yanlei
理由：结直肠癌（CRC）是所有癌症中发病率第三高的恶性肿瘤。在宿主基因组成和环境暴露的驱动下，肠道微生物群及其代谢物被认为是结直肠癌发病的原因和调节因子。我们评估了人类粪便样本作为无创和无偏倚的替代品，以编目结直肠癌患者的肠道微生物群和代谢组。方法：收集结直肠癌患者（CRC组，n = 50）和健康志愿者（H组，n = 50）的粪便样本，进行微生物组（16S rRNA基因测序）和代谢组（气相色谱-质谱联用）分析。使用各种生物信息学方法对数据集进行单独分析和综合分析。结果：粪便代谢组学分析鉴定出164种代谢物，分布在两组的40种代谢途径中。此外，H组和CRC组分别有42种和17种代谢物。微生物多样性测序结果显示，两组间共有1084个操作分类单位（otu）， CRC组的物种多样性低于H组。在H志愿者和CRC患者的微生物群中鉴定出76个歧视性otu。综合分析将crc相关微生物与代谢物，如多胺（尸胺和腐胺）联系起来。结论：我们的研究结果提供了大量证据，证明肠道微生物组和代谢组（即多胺）之间存在一种新的相互作用，这种相互作用在结直肠癌中受到严重干扰。微生物相关代谢物可作为诊断性生物标志物用于治疗探索。
Rationale: Colorectal cancer (CRC) is a malignant tumor with the third highest morbidity rate among all cancers. Driven by the host's genetic makeup and environmental exposures, the gut microbiome and its metabolites have been implicated as the causes and regulators of CRC pathogenesis. We assessed human fecal samples as noninvasive and unbiased surrogates to catalog the gut microbiota and metabolome in patients with CRC.Methods: Fecal samples collected from CRC patients (CRC group, n = 50) and healthy volunteers (H group, n = 50) were subjected to microbiome (16S rRNA gene sequencing) and metabolome (gas chromatography-mass spectrometry, GC-MS) analyses. The datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches.Results: Fecal metabolomic analysis led to the identification of 164 metabolites spread across 40 metabolic pathways in both groups. In addition, there were 42 and 17 metabolites specific to the H and CRC groups, respectively. Sequencing of microbial diversity revealed 1084 operational taxonomic units (OTUs) across the two groups, and there was less species diversity in the CRC group than in the H group. Seventy-six discriminatory OTUs were identified for the microbiota of H volunteers and CRC patients. Integrated analysis correlated CRC-associated microbes with metabolites, such as polyamines (cadaverine and putrescine).Conclusions: Our results provide substantial evidence of a novel interplay between the gut microbiome and metabolome (i.e., polyamines), which is drastically perturbed in CRC. Microbe-associated metabolites can be used as diagnostic biomarkers in therapeutic explorations.