Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia
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 gastri...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2015
|
| Online Access: | http://hdl.handle.net/1721.1/99201 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1826198563790520320 |
|---|---|
| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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. |
| author_sort | Lofgren, Jennifer L. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:06:50Z |
| format | Article |
| id | mit-1721.1/99201 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:06:50Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/992012022-09-27T17:13:01Z Lack of Commensal Flora in H. 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 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. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Lofgren, Jennifer L. Whary, Mark T. Ge, Zhongming Muthupalani, Sureshkumar Taylor, Nancy S. Mobley, Melissa W. Potter, Amanda Fox, James G. 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. National Institutes of Health (U.S.) (Grant R01 AI37750) National Institutes of Health (U.S.) (Grant R01 CA093405) National Institutes of Health (U.S.) (Grant P30 ES02109) National Institutes of Health (U.S.) (Grant P01 CA028842) National Institutes of Health (U.S.) (Grant T32 RR07036) 2015-10-08T13:13:18Z 2015-10-08T13:13:18Z 2010-10 2010-08 Article http://purl.org/eprint/type/JournalArticle 00165085 1528-0012 http://hdl.handle.net/1721.1/99201 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. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1053/j.gastro.2010.09.048 Gastroenterology Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | 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. Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title | Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title_full | Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title_fullStr | Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title_full_unstemmed | Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title_short | Lack of Commensal Flora in H. pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia |
| title_sort | lack of commensal flora in h pylori infected ins gas mice reduces gastritis and delays intraepithelial neoplasia |
| url | http://hdl.handle.net/1721.1/99201 https://orcid.org/0000-0001-9307-6116 |
| work_keys_str_mv | AT lofgrenjenniferl lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT wharymarkt lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT gezhongming lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT muthupalanisureshkumar lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT taylornancys lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT mobleymelissaw lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT potteramanda lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT varroandrea lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT eibachdaniel lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT suerbaumsebastian lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT wangtimothyc lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT foxjamesg lackofcommensalflorainhpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT lofgrenjenniferl lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT wharymarkt lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT gezhongming lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT muthupalanisureshkumar lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT taylornancys lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT mobleymelissaw lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT potteramanda lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT varroandrea lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT eibachdaniel lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT suerbaumsebastian lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT wangtimothyc lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia AT foxjamesg lackofcommensalflorainhelicobacterpyloriinfectedinsgasmicereducesgastritisanddelaysintraepithelialneoplasia |