Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia.
Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia.
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DOI：
10.1053/j.gastro.2010.09.048
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发表时间：
2011-01
期刊：
影响因子：
29.4
通讯作者：
Fox JG
中科院分区：
文献类型：
--
作者：
Lofgren JL;Whary MT;Ge Z;Muthupalani S;Taylor NS;Mobley M;Potter A;Varro A;Eibach D;Suerbaum S;Wang TC;Fox JG
转基因胰岛素-胃泌素（INS-GAS）小鼠具有高循环水平的胃泌素。在FVB/N背景下，这些小鼠在幽门螺杆菌感染后6个月发生自发性萎缩性胃炎和胃肠道上皮内瘤变（GIN），患病率为80%。GIN与胃萎缩和无氯血症相关，使小鼠易患非有益菌微生物群过度生长。我们确定了无菌INS-GAS小鼠是否自发地发展GIN，以及H。pylori加速gnotobiotic INS-GAS小鼠的GIN。我们比较了无菌和H. pylori单感染的INS-GAS小鼠。通过焦磷酸测序对无特定病原体（SPF）INS-GAS小鼠的微生物群组成进行定量。无菌INS-GAS小鼠有轻度高胃泌素血症，但直到9个月大时才出现明显的胃部病变; 13个月大时才出现GIN。H. pylori单相关性在感染后5 - 11个月引起进行性胃炎、上皮缺陷、泌酸腺萎缩、显著的小凹增生和发育不良以及强烈的血清和组织促炎免疫应答（特别是在雄性小鼠中）（与无菌对照相比，P<0.05）。26例女性中仅有2例H.幽门螺杆菌感染的INS-GAS小鼠在感染后11个月发展为低至高级别的GIN。H的胃幽门螺杆菌感染的SPF雄性小鼠的拟杆菌显著减少，厚壁菌显著增加。无菌INS-GAS小鼠的胃病变比雄性SPF INS-GAS小鼠长13个月。H.与H. pylori单结合相比，H. pylori单结合加速胃炎和GIN，但引起的胃损害不太严重，GIN的发病延迟。幽门螺杆菌感染的INS-GAS小鼠具有复杂的胃微生物群。胃内菌群组成的改变可能促进SPF小鼠胃酸缺乏胃中的GIN。
Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice.
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影响因子：
29.4
作者：
Fox, JG;Li, XT;Wang, TC
通讯作者：
Wang, TC
影响因子：
3.1
作者：
Khamri, Wafa;Walker, Marjorie M.;Lombardi, Giovanna
通讯作者：
Lombardi, Giovanna
影响因子：
82.9
作者：
Fox, JG;Beck, P;Nagler-Anderson, C
通讯作者：
Nagler-Anderson, C
影响因子：
3.1
作者：
Lee, Chung-Wei;Rao, Varada P.;Fox, James G.
通讯作者：
Fox, James G.
影响因子：
3.1
作者：
FOX, JG;LEE, A;MURPHY, JC
通讯作者：
MURPHY, JC