胃液微生物研究进展

  • 2017-09-26 10:57:37
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1.胃液微生物研究进展


1.1幽门螺杆菌(Helicobacter pylori)与胃癌


国际癌症研究机构已经将幽门螺杆菌作为人类一级致癌物。幽门螺杆菌中藏有许多具有致病性的毒力因子[1],常见的有VacA蛋白[2-5]CagA蛋白[6]VacA蛋白存在于所有幽门螺杆菌的菌株中[7],并且可能通过线粒体干扰诱导目标宿主细胞孔形成,促进胃上皮细胞凋亡[8]。与VacA不同Cag致病岛内的一系列基因并不存在于每一个幽门螺杆菌菌株中,它是从IV型细菌分泌系统(T4SS)中将Cag致病岛内的基因编码蛋白质,并将细菌成分注入到宿主细胞中。Cag致病岛的存在阻碍了巨噬细胞吞噬幽门螺杆菌的有效性[9, 10]。除此之外,一系列新确定的因子也被假定为能够促进幽门螺杆菌诱导上皮细胞损伤的能力。这些因子包括十二指肠溃疡促进与IL-8产物增加相关的抗原,某些种群增加十二指肠溃疡风险,有助于幽门螺杆菌定植的血型抗原结合黏附素[11]


1.2 胃液菌群的变化


有很长一段时间,由于酸性环境而被认为胃液中没有微生物。但幽门螺杆菌的存在打破了这一误解。其实胃黏液中形成了一个pH梯度,因此使得微生物免受酸攻击。Dicksved等人[12]研究发现胃环境中存在5类代表性细菌,包括Firmicutes, Bacteroidetes, Proteobacteria, ActinobacteriaFusobacteria门。属水平上,Streptococcus, Lactobacillus, VeillonellaPrevotella占据主导地位。Eun和他的同事[13]利用焦磷酸测序技术研究发现胃癌、肠上皮化生(IM)和慢性胃炎患者之间的微生物群落存在显著性差异。Aviles-Jiminez等人研究发现从非萎缩性胃炎(NAG)发展到肠上皮化生(IM)直至胃癌(GC),其胃液微生物群落结构逐渐发生改变[14]。也有研究者证明了酸抑制剂药物治疗会导致胃中整体细菌负荷增加,一旦停止治疗即会恢复正常[15]


1.3胃液中的益生菌

    

      乳酸菌(Lactobacillus)和双歧杆菌(Bifidobacterium)是最常见的益生菌。研究表明胃内这些“友好”菌能够增强幽门螺杆菌试图逃避的免疫反应[16]。这些益生菌可以与toll样受体结合,在上皮细胞表面表达,并触发免疫防御机制的级联[16]。益生菌与上皮细胞之间的相互作用会导致炎症性细胞因子产物的调制,从而减少胃黏膜炎症。


参考文献:

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[13]Chang S E, Byung K K, Dong S H, et al. Differences in Gastric Mucosal Microbiota Profiling in Patients with Chronic Gastritis, Intestinal Metaplasia, and Gastric Cancer Using Pyrosequencing Methods[J]. Helicobacter, 2014, 19(6):407-416.

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[16]Russo F, Linsalata M, Orlando A. Probiotics against neoplastic transformation of gastric mucosa:Effects on cell proliferation and polyamine metabolism[J]. World Journal of Gastroenterology, 2014, 20(37):13258-13272.

 

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