Helicobacter felis–Associated Gastric Disease in Microbiota-Restricted Mice

Abstract

SummaryHuman Helicobacter pylori infection leads to multiple pathological consequences, including gastritis and adenocarcinoma. Although this association has led to the classification of H. pylori as a type 1 carcinogen, it is not clear if additional nonhelicobacter gastric microbiota play a role in these diseases. In this study, we utilized either specific pathogen-free C57BL/6 mice (B6.SPF) or mice colonized with altered Schaedler flora (B6.ASF) to evaluate the role of nonhelicobacter gastric microbiota in disease development after Helicobacter felis infection. Despite similar histological changes, H. felis persisted in B6.ASF stomachs, while H. felis could no longer be detected in the majority of B6.SPF mice. The B6.SPF mice also acquired multiple Lactobacillus spp. in their stomachs after H. felis infection. Our data indicate that potential mechanisms responsible for the ineffective H. felis clearance in the B6.ASF model include the absence of new gastric microbiota to compete for the gastric niche, the lack of expression of new gastric mucins, and a reduced ratio of H. felis-specific IgG2c:IgG1 serum antibodies. These data suggest that although H. felis is sufficient to initiate gastric inflammation and atrophy, bacterial eradication and the systemic immune response to infection are significantly influenced by pre-existing and acquired gastric microbiota. (J Histochem Cytochem 59:826-841, 2011)

Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in theHelicobacter pyloriINS-GAS mouse model of gastric carcinogenesis

“…Interestingly, greater microbial diversity of IF was associated with lower Hp colonisation compared with rASF colonisation or Hp monoassociation, a result consistent with studies using H felis- infected gnotobiotic C57BL/6 mice 41. In addition to the inhibitory effects of inflammation on Hp , the microbiota of the IF-colonised mice was SPF, but otherwise undefined, and thus unidentified bacteria may have out-competed and lowered Hp colonisation.…”

“…These shifts in gastric microbiota were associated with decreased Hp colonisation. It has been shown that Lactobacillus casei inhibits Hp colonisation 41. Recently, investigators using H pylori -infected C57BL mice from two commercial sources noted that mice from one commercial source had significantly higher gastric inflammation scores than the mice from the second source despite similar H pylori colonisation in mice from both sources 42.…”

The role of the gastrointestinal microbiome inHelicobacter pyloripathogenesis

“…The difficulty in establishing infection in mice 101,103 109 When infection is achieved, H. pylori represent 10-30% of the microbiota in the absence of significant pathology and <5% of the bacteria in stomachs with significant disease. 72,77 The decreasing levels highlights an inverse correlation between H. pylori levels and the degree of gastric pathology that is commonly observed in mice.…”

The gastric microbial community,Helicobacter pyloricolonization, and disease

“…39 A complex gut microbiota has also been associated with enhanced clearance of H. felis, another gastric helicobacter. 40 However, studies performed by us and others that have looked for similar vendor or antibiotic effects on H. pylori colonization have met with negative results. A single strain of mouse purchased from different laboratories can have profoundly different microbiota and immune profiles in the lower GI tract, 41 yet carry similar levels of H. pylori in the stomach.…”