Abstract
BackgroundGastrointestinal (GI) inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far.Methodology/Principal FindingsFor the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or its isogenic ΔcagY mutant (MUT) strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils.Conclusion/SignificanceTaken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled.
Highlights
Chronic Helicobacter (H.) pylori infection represents a significant health burden affecting approximately half of the world’s population [1]
In H. pylori WT and MUT infected animals, gastric pathology was characterized by lymphoid aggregates in the antrum (100% with either strain) and corpus (100% and 33.3%, respectively), erosions (100% and 83.3%, respectively), ulcers (75.0% and 0%, respectively), parietal cell atrophy (100% and 33.3%, respectively), and metaplastic changes (90.9% and 33.3%, respectively), gastritic cystica profunda (75.0% and 33.3%, respectively), and focal dysplasia (25.0% and 0%, respectively) (Fig. 1, Table 1)
In the study presented here we performed a comprehensive survey of microbiota changes along the entire GI tract in Mongolian gerbils following long-term infection with H. pylori for 14 months comparing B8 wildtype with its isogenic cagY mutant strain defective in the type IV secretion system
Summary
Chronic Helicobacter (H.) pylori infection represents a significant health burden affecting approximately half of the world’s population [1]. The H. pylori mutant DcagY is defective in the T4SS, representing a less virulent strain, which lacks the ability to induce a corpus dominant atrophic gastritis as confirmed in our previous Mongolian gerbil study [9]. Following H. pylori infection of gerbils, like in humans the gastric inflammatory process starts in the antrum mucosa and further expands to the corpus whereas in infected mice the antrum is rarely involved. H. pylori type I strains expressing CagA, VacA and a functional type IV secretion system only persist in a Mongolian gerbil, but not murine stomach in a genetically stable fashion. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, have not been studied so far
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