Lack of Commensal Flora in Helicobacter pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia

幽门螺杆菌 胃炎 胃泌素 萎缩性胃炎 螺杆菌 胃粘膜 生物 肠化生 促炎细胞因子 胃肠病学 内科学 免疫学 医学 炎症 分泌物
作者
Jennifer L Lofgren,Mark T. Whary,Zhongming Ge,Sureshkumar Muthupalani,Nancy S. Taylor,Melissa W. Mobley,Amanda Potter,Andrea Varró,Daniel Eibach,Sebastian Suerbaum,Timothy C. Wang,James G. Fox
出处
期刊:Gastroenterology [Elsevier BV]
卷期号:140 (1): 210-220.e4 被引量:353
标识
DOI:10.1053/j.gastro.2010.09.048
摘要

Background & AimsTransgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and 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 nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice.MethodsWe compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori–monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing.ResultsGermfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P<0.05, compared with germfree 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 postinfection. Stomachs of H pylori–infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes.ConclusionsGastric lesions take 13 months longer to develop in germfree 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 with H pylori–infected INS-GAS mice with complex gastric microbiota. Changes in gastric microbiota composition might promote GIN in achlorhydric stomachs of SPF mice. Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and 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 nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice. We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori–monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing. Germfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P<0.05, compared with germfree 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 postinfection. 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 germfree 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 with H pylori–infected INS-GAS mice with complex gastric microbiota. Changes in gastric microbiota composition might promote GIN in achlorhydric stomachs of SPF mice.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
YIXIN发布了新的文献求助10
1秒前
1秒前
jacs111发布了新的文献求助10
2秒前
2秒前
陈开山发布了新的文献求助30
2秒前
3秒前
3秒前
何以故人初完成签到 ,获得积分10
3秒前
金银角上头的完成签到,获得积分10
3秒前
4秒前
4秒前
耿春丽完成签到,获得积分10
4秒前
4秒前
6秒前
weilu发布了新的文献求助10
6秒前
7秒前
嘟嘟发布了新的文献求助10
8秒前
陈开山完成签到,获得积分10
8秒前
梨理栗发布了新的文献求助10
8秒前
8秒前
alex发布了新的文献求助10
9秒前
9秒前
LaTeXer应助隐形夕阳采纳,获得50
9秒前
lw发布了新的文献求助10
10秒前
10秒前
英姑应助Janusfaces采纳,获得10
10秒前
10秒前
plasmid完成签到,获得积分10
11秒前
Ava应助咕噜咕噜咕嘟咕嘟采纳,获得10
11秒前
12秒前
SHAO应助一块司康饼采纳,获得100
12秒前
嗯哼发布了新的文献求助10
12秒前
Rondab应助mariawang采纳,获得10
14秒前
MchemG应助酷酷的紫南采纳,获得30
15秒前
1111发布了新的文献求助10
15秒前
15秒前
continue发布了新的文献求助10
16秒前
zhangtong发布了新的文献求助10
16秒前
嘟嘟完成签到,获得积分10
16秒前
wdy111应助葡萄味的果茶采纳,获得20
17秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021