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

Microbiol Spectr. 2024 Jan 11;12(1):e0345023. doi: 10.1128/spectrum.03450-23. Epub 2023 Nov 28.

Abstract

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.

Keywords: Cutibacterium acnes; Helicobacter pylori; Mus musculus; gnotobiotic mouse model; mouse model of H. pylori-induced gastric cancer; non-H. pylori gastric bacteria; thiopeptide.

MeSH terms

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

Substances

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