Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia
Name
Fox_Lack commensal.pdf
Size
2.61 MB
Format
Adobe PDF
Checksum (MD5)
abf062826242a0c43f3f36279313e26a
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
Alternative Title
Lack of Commensal Flora in Helicobacter pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia
Date Issued
October 2010
Journal
Gastroenterology
Publisher
Elsevier
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
Terms of Use
Creative Commons Attribution-Noncommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1053/j.gastro.2010.09.048
