A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy.
A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy.
复制标题
使用合并的MAS 1HNMR和metataxonomic策略对结直肠癌中粘膜微生物组 - 米组组相互作用进行了前瞻性分析。
DOI：
10.1038/s41598-017-08150-3
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发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Marchesi JR
中科院分区：
文献类型：
--
作者：
Kinross J;Mirnezami R;Alexander J;Brown R;Scott A;Galea D;Veselkov K;Goldin R;Darzi A;Nicholson J;Marchesi JR
结肠癌会导致肠道微生物区系中与之相关的特定生态位改变，从而导致粘膜生物失调。然而，这些细菌的关键代谢功能仍不清楚。我们在没有机械肠道准备的结肠癌择期手术患者中进行了一项前瞻性观察研究(n = 18)。利用16 S核糖核酸基因测序，我们证明了微生物区系生态学似乎具有肿瘤分期特异性，并与预后不良的组织学特征密切相关。梭杆菌(p <； 0.007)和ε-变形杆菌(p <； 0.01)与癌旁正常粘膜组织相比，肿瘤组织中的含量较高，且梭菌和β-变形杆菌的水平随着肿瘤分期的进展而增加(p = 分别为0.014和0.002)。利用1H魔角旋转核磁共振波谱进行的代谢组学分析表明，与邻近的健康组织相比，肿瘤中牛磺酸、异谷氨酰胺、胆碱、乳酸、苯丙氨酸和酪氨酸的丰度增加，而脂质和甘油三酯的水平降低。网络分析表明，与预后不良相关的细菌并不是癌症粘膜代谢组修饰的原因。因此，结肠癌黏膜微生物组随着癌症的分期而进化，以满足癌症代谢的需要。乘客微生物区系可能在维持癌症粘膜代谢动态平衡中发挥作用，但这些代谢功能可能不是阶段特异性的。
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis. Fusobacteria (p < 0.007) and ε- Proteobacteria (p < 0.01) were enriched on tumour when compared to adjacent normal mucosal tissue, and fusobacteria and β-Proteobacteria levels increased with advancing cancer stage (p = 0.014 and 0.002 respecitvely). Metabonomic analysis using 1H Magic Angle Spinning Nuclear Magnetic Resonsance (MAS-NMR) spectroscopy, demonstrated increased abundance of taurine, isoglutamine, choline, lactate, phenylalanine and tyrosine and decreased levels of lipids and triglycerides in tumour relative to adjacent healthy tissue. Network analysis revealed that bacteria associated with poor prognostic features were not responsible for the modification of the cancer mucosal metabonome. Thus the colon cancer mucosal microbiome evolves with cancer stage to meet the demands of cancer metabolism. Passenger microbiota may play a role in the maintenance of cancer mucosal metabolic homeostasis but these metabolic functions may not be stage specific.