Gastric coinfection with thiopeptide-positive Cutibacterium acnes decreases FOXM1 and pro-inflammatory biomarker expression in a murine model of Helicobacter pylori-induced gastric cancer.

Abstract

IMPORTANCE:

H. pylori infects half of the world population and is the leading cause of gastric cancer. We previously demonstrated that gastric cancer risk is associated with gastric microbiota. Specifically, gastric urease-positive Staphylococcus epidermidis and Streptococcus salivarius had contrasting effects on H. pylori-associated gastric pathology and immune responses in germ-free INS-GAS mice. As gastritis progresses to gastric cancer, the oncogenic transcription factor Foxm1 becomes increasingly expressed. In this study, we evaluated the gastric commensal C. acnes, certain strains of which produce thiopeptides that directly inhibit FOXM1. Thiopeptide-positive C. acnes was isolated from Nicaraguan patient gastric biopsies and inoculated into germ-free INS-GAS mice with H. pylori. We, therefore, asked whether coinfection with C. acnes expressing thiopeptide and H. pylori would decrease gastric Foxm1 expression and pro-inflammatory cytokine mRNA and protein levels. Our study supports the growing literature that specific non-H. pylori gastric bacteria affect inflammatory and cancer biomarkers in H. pylori pathogenesis.

• Authors: Courtney Lunger, Zeli Shen, Hilda Holcombe, Anthony J Mannion, JoAnn Dzink-Fox, Susanna Kurnick, Yan Feng, Sureshkumar Muthupalani, Sebastian E Carrasco, Keith T Wilson, Richard M Peek, M Blanca Piazuelo, Douglas R Morgan, Amanda L Armijo, Melissa Mammoliti, Timothy C Wang, James G Fox
• Journal: Microbiology spectrum (Microbiol Spectr) Vol. 12 Issue 1 Pg. e0345023 (Jan 11 2024) ISSN: 2165-0497 [Electronic] United States
• PMID: 38014984 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• FOXM1 protein, human
• Forkhead Box Protein M1

Topics

• Humans
• Mice
• Animals
• Helicobacter pylori
• Stomach Neoplasms (metabolism, microbiology, pathology)
• Coinfection
• Disease Models, Animal
• Biomarkers, Tumor
• Helicobacter Infections (complications, microbiology, pathology)
• Forkhead Box Protein M1 (genetics)