期刊
GASTROENTEROLOGY
卷 140, 期 1, 页码 210-+出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2010.09.048
关键词
Microbiome; Hypergastrinemic Mice; Gastric Adenocarcinoma; Enteric Microbiota
资金
- German Research Foundation [SFB621/B8, SFB 900/Z1]
- [R01 AI37750]
- [R01 CA093405]
- [P30 ES02109]
- [P01 CA028842]
- [T32 RR07036]
- NATIONAL CANCER INSTITUTE [R01CA093405, P01CA028842] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [T32RR007036] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI037750] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES002109] Funding Source: NIH RePORTER
BACKGROUND & AIMS: 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 over-growth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice. METHODS: We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori-monoinfected INS-GAS mice. Micro-biota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing. RESULTS: 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. CONCLUSIONS: 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.
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