幽门螺旋杆菌致癌蛋白cagA促进与癌变相关的胃部菌群失调
创作:szx 审核:szx 2019年06月10日
  • 致癌蛋白cagA、缺铁、胃部菌群失调等因素可增加幽门螺旋杆菌(Hp)感染后的胃癌风险;
  • 蒙古沙鼠感染致癌性cag+ Hp菌株7.13或7.13的cagA突变体;
  • 感染了Hp的蒙古沙鼠胃部炎症及损伤显著增加,胃部菌群组成改变且α多样性显著降低,这一表型依赖于cagA;
  • 缺铁增加了Hp感染引起的胃部损伤,但未显著影响Hp感染后的胃部菌群组成及α、β多样性;
  • 胃部菌群的α及β多样性与胃部的恶性病变相关。
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szx
幽门螺旋杆菌感染时胃癌的一大风险因素,但并非所有感染了幽门螺旋杆菌的个体均会发展出胃癌。来自mBio上发表的一项最新研究,发现幽门螺旋杆菌产生的一种致癌蛋白cagA可促进蒙古沙鼠的胃部菌群失调,且胃部菌群失调与胃部恶性病变相关。
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mBio [IF:6.784]

Modification of the Gastric Mucosal Microbiota by a Strain-Specific Helicobacter pylori Oncoprotein and Carcinogenic Histologic Phenotype

菌株特异性幽门螺旋杆菌致癌蛋白及致癌组织学表型对胃粘膜菌群的影响

10.1128/mBio.00955-19

2019-05-28, Article

Abstract & Authors:展开

Abstract:收起
Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+ H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease.

First Authors:
Jennifer M Noto

Correspondence Authors:
Richard M Peek Jr

All Authors:
Jennifer M Noto,Joseph P Zackular,Matthew G Varga,Alberto Delgado,Judith Romero-Gallo,Matthew B Scholz,M Blanca Piazuelo,Eric P Skaar,Richard M Peek Jr

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