Gastric colonization with intestinal flora (IF) has been shown to promote Helicobacter pylori (Hp)-associated gastric cancer.
However, it is unknown if the mechanism involves colonization with specific or diverse microbiota secondary to gastric atrophy.
Dr James Fox and colleagues from Massachussetts, USA correlated gastric colonization with Altered Schaedler's flora (ASF) and Helicobacter pylori with pathology, immune responses and mRNA expression for proinflammatory and cancer-related genes in germ-free (GF), Hp monoassociated (mHp), restricted ASF (rASF; 3 species), and specific pathogen-free (complex IF), hypergastrinemic INS-GAS mice 7 months postinfection.
Male mice cocolonized with rASF Helicobacter pylori or IF Helicobacter pylori developed the most severe pathology.
IFHelicobacter pylori males had the highest inflammatory responses, and 40% developed invasive gastrointestinal intraepithelial neoplasia.
|Helicobacter pylori colonization also elevated expression of cancer-related genes|
The team noted that rASF Helicobacter pylori colonization was highest in males and 23% developed invasive gastrointestinal intraepithelial neoplasia with elevated expression of inflammatory biomarkers.
The researchers observed that lesions were less severe in females and none developed gastrointestinal intraepithelial neoplasia.
Gastritis in male rASF Helicobacter pylori mice was accompanied by decreased Clostridum species ASF356 and Bacteroides species ASF519 colonization, and an overgrowth of Lactobacillus murinus ASF361, supporting that inflammation-driven atrophy alters the gastric niche for GI commensals.
The team observed that Helicobacter pylori colonization also elevated expression of IL-11 and cancer-related genes, Ptger4 and Tgf-ß, further supporting that Helicobacter pylori infection accelerates gastric cancer development in INS-GAS mice.
Dr Fox's team concludes, "rASF Helicobacter pylori colonization was sufficient for GIN development in males, and lower gastrointestinal intraepithelial neoplasia incidence in females was associated with lower inflammatory responses and gastric commensal and Helicobacter pylori colonization."
"Colonization efficiency of commensals appears more important than microbial diversity and lessens the probability that specific gastrointestinal pathogens are contributing to cancer risk."