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.
abstract: 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(+) 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(+) 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.
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mwhary@mit.edu.
authors: Mark T
authors: MT
authors: Whary
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Sureshkumar
authors: S
authors: Muthupalani
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Zhongming
authors: Z
authors: Ge
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Yan
authors: Y
authors: Feng
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Jennifer
authors: J
authors: Lofgren
authors: Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Hai Ning
authors: HN
authors: Shi
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Nancy S
authors: NS
authors: Taylor
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: Pelayo
authors: P
authors: Correa
authors: Department of Pathology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
authors: James
authors: J
authors: Versalovic
authors: Division of Digestive and Liver Disease, Columbia University Medical Center, New York, NY, USA.
authors: Timothy C
authors: TC
authors: Wang
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: James G
authors: JG
authors: Fox
mesh_terms: D000818:Animals; D001284:Atrophy; D060085:Coinfection / Q000473:pathology*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D005753:Gastric Mucosa / Q000473:pathology*; D016481:Helicobacter Infections / Q000150:complications* / Q000473:pathology*; D006373:Helminthiasis / Q000150:complications* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064307:Microbiota
keywords: Altered Schaedler Flora; Gastric cancer; Helicobacter pylori; Heligmosomoides polygyrus; INS-GAS mice