Nat Commun:结直肠癌患者的肠道细菌分泌丁酸盐,促进肿瘤的形成

2021-09-30 haibei MedSci原创

最近,研究人员在两个独立的队列研究中发现,12种粪便细菌分类群在CRC患者中富集。

在过去的几十年里,随着饮食的变化和寿命的延长,结直肠癌(CRC)的发病率和死亡率一直在急剧上升,CRC现在已经成为全球排名第二的最常见的癌症。因此,人们迫切需要针对CRC的有效措施,以帮助CRC的早期检测和预防

在健康的成年人中,结肠含有最密集的代谢活跃的微生物群落。人们越来越清楚的是,肠道微生物群组成的变化与各种疾病有关,包括癌症。例如,在ApcMin/+小鼠中引入核酸镰刀菌(Fusobacterium nucleatum)或脆弱细菌(Bacteroides fragilis)会加速肠道肿瘤的发生。此外,据报道,pks+大肠杆菌、厌氧链球菌、梭状芽孢杆菌和脆弱细菌分别通过产生colibactin,激活PI3K-AKT途径、产生次级胆汁酸和脆弱细菌毒素来促进结肠肿瘤的形成。因此,利用肠道微生物群进行CRC筛查和/或CRC预防正引起人们的热切关注。

然而,由于居住区域、医疗和技术方案会强烈影响人类肠道微生物群的变化,因此目前很难整合和比较不同的已发表数据。更重要的是,尽管许多研究报道了某些肠道细菌的丰度在CRC患者中增加或减少,但除了上述的细菌种类外,人们并不清楚这些肠道细菌中哪些实际上参与了CRC的发展。

因此,为了更好地了解结直肠癌的发生机制,并开发更有效的CRC筛查方法,我们有必要明确在结直肠癌患者体内增加或减少的肠道细菌中,哪些细菌实际上参与了CRC的发展,以及它们如何发挥这些作用。为此,我们需要一些可靠的指标,以检测潜在的致癌刺激物。

结直肠癌患者体内富集的肠道微生物种类

最近,研究人员在两个独立的队列研究中发现,12种粪便细菌分类群在CRC患者中富集。其中,2种卟啉菌能够通过分泌细菌代谢物丁酸盐诱导细胞衰老,这是一种致癌的应激反应。

值得注意的是,在CRC组织中观察到这些细菌的入侵,与丁酸盐水平的升高和衰老相关的炎症表征相吻合。此外,尽管向ApcΔ14/+小鼠施用这些细菌会加速结直肠肿瘤的发生,但当细菌的丁酸盐合成基因被破坏时,情况并非如此。

因此,这些结果综合表明,卟啉单胞菌的过度生长和结直肠肿瘤的发生之间存在因果关系,这可能是由于丁酸盐诱导的衰老所致的。

 

原始出处:

Shintaro Okumura et al. Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion. Nature Communications (2021). 

 

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    2022-09-17 小小医者

    #结直肠癌#患者的肠道细菌分泌#丁酸盐#,促进#肿瘤#的形成,这是一个反例,与一般认知的#肠道微生物#不一样,未来还需要更多的研究。一般认为丁酸盐是有益的

    0

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    2021-10-05 liye789132251
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    2022-08-01 liuli5079
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