Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota
Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastri...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/99365 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1826215948593397760 |
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| author | Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer L. Shi, Hai Ning Taylor, Nancy S. Correa, Pelayo Versalovic, James 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 Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer L. Shi, Hai Ning Taylor, Nancy S. Correa, Pelayo Versalovic, James Wang, Timothy C. Fox, James G. |
| author_sort | Whary, Mark T. |
| collection | MIT |
| description | Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3[superscript +] cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3[superscript +] cells in the corpus and reduced H. pylori-associated gastric atrophy (p < 0.04), dysplasia (p < 0.02) and prevented H. pylori-induced changes in the gastric flora (p < 0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. |
| first_indexed | 2024-09-23T16:40:02Z |
| format | Article |
| id | mit-1721.1/99365 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:40:02Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/993652022-09-29T20:37:37Z Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer L. Shi, Hai Ning Taylor, Nancy S. Correa, Pelayo Versalovic, James Wang, Timothy C. Fox, James G. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer L. Taylor, Nancy S. Fox, James G. Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3[superscript +] cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3[superscript +] cells in the corpus and reduced H. pylori-associated gastric atrophy (p < 0.04), dysplasia (p < 0.02) and prevented H. pylori-induced changes in the gastric flora (p < 0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. RO1-CA67529 R01DK052413 PO1CA26731 P01 CA028842 P30ESO2109 R01DK065075 2015-10-20T12:09:35Z 2015-10-20T12:09:35Z 2014-02 2013-11 Article http://purl.org/eprint/type/JournalArticle 12864579 http://hdl.handle.net/1721.1/99365 Whary, Mark T., Sureshkumar Muthupalani, Zhongming Ge, Yan Feng, Jennifer Lofgren, Hai Ning Shi, Nancy S. Taylor, et al. “Helminth Co-Infection in Helicobacter Pylori Infected INS-GAS Mice Attenuates Gastric Premalignant Lesions of Epithelial Dysplasia and Glandular Atrophy and Preserves Colonization Resistance of the Stomach to Lower Bowel Microbiota.” Microbes and Infection 16, no. 4 (April 2014): 345–55. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1016/j.micinf.2014.01.005 Microbes and Infection Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer L. Shi, Hai Ning Taylor, Nancy S. Correa, Pelayo Versalovic, James Wang, Timothy C. Fox, James G. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title | Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title_full | Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title_fullStr | Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title_full_unstemmed | Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title_short | Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| title_sort | helminth co infection in helicobacter pylori infected ins gas mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota |
| url | http://hdl.handle.net/1721.1/99365 https://orcid.org/0000-0001-9307-6116 |
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