Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia
Author(s)Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa W.; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.; ... Show more Show less
Lack of Commensal Flora in Helicobacter pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia
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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 overgrowth. 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. Microbiota 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.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative Medicine
Lofgren, Jennifer L., Mark T. Whary, Zhongming Ge, Sureshkumar Muthupalani, Nancy S. Taylor, Melissa Mobley, Amanda Potter, et al. “Lack of Commensal Flora in Helicobacter pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia.” Gastroenterology 140, no. 1 (January 2011): 210–220.e4.
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