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Helicobacter pylori infection is associated with an altered gastric microbiota in children.

ABSTRACT: The intestinal microbiome in early life influences development of the mucosal immune system and predisposition to certain diseases. Because less is known about the microbiome in the stomach and its relationship to disease, we characterized the microbiota in the stomachs of 86 children and adults and the impact of Helicobacter pylori infection on the bacterial communities. The overall composition of the gastric microbiota in children and adults without H. pylori infection was similar, with minor differences in only low abundance taxa. However, the gastric microbiota in H. pylori-infected children, but not infected adults, differed significantly in the proportions of multiple high abundance taxa compared with their non-infected peers. The stomachs of H. pylori-infected children also harbored more diverse microbiota, smaller abundance of Firmicutes, and larger abundance of non-Helicobacter Proteobacteria and several lower taxonomic groups than stomachs of H. pylori-infected adults. Children with restructured gastric microbiota had higher levels of FOXP3, IL10, and TGF? expression, consistent with increased T-regulatory cell responses, compared with non-infected children and H. pylori-infected adults. The gastric commensal bacteria in children are altered during H. pylori infection in parallel with more tolerogenic gastric mucosae, potentially contributing to the reduced gastric disease characteristic of H. pylori-infected children.

SUBMITTER: Brawner KM

PROVIDER: S-EPMC5526746 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Helicobacter pylori infection is associated with an altered gastric microbiota in children.

Brawner K M KM Kumar R R Serrano C A CA Ptacek T T Lefkowitz E E Morrow C D CD Zhi D D Kyanam-Kabir-Baig K R KR Smythies L E LE Harris P R PR Smith P D PD

Mucosal immunology 20170125 5

The intestinal microbiome in early life influences development of the mucosal immune system and predisposition to certain diseases. Because less is known about the microbiome in the stomach and its relationship to disease, we characterized the microbiota in the stomachs of 86 children and adults and the impact of Helicobacter pylori infection on the bacterial communities. The overall composition of the gastric microbiota in children and adults without H. pylori infection was similar, with minor ...[more]

PMID: 28120843

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Project description:ObjectiveThe present study aims to investigate the effect of Helicobacter pylori (Hp) infection on gastric mucosal microbiota in patients with chronic gastritis.MethodsHere recruited a population of 193 patients with both chronic gastritis and positive rapid urease, including 124 patients with chronic atrophic gastritis (CAG) and 69 patients with chronic non-atrophic gastritis (nCAG). Immunoblotting was used to detect four serum Hp antibodies (UreA, UreB, VacA and CagA) to determine the types of virulent Hp-I and avirulent Hp-II infections. Gastric microbiota was profiled by 16S rRNA gene V3-V4 region, and R software was used to present the relationship between the microbial characteristics and the type of Hp infection.ResultsIn the stomach of patients with Hp-positive gastritis, the dominant gastric bacterial genera included Ralstonia (23.94%), Helicobacter (20.28%), Pseudonocardia (9.99%), Mesorhizobium (9.21%), Bradyrhizobium (5.05%), and Labrys (4.75%). The proportion of Hp-I infection was significantly higher in CAG patients (91.1%) than in nCAG patients (71.0%) (P < 0.001). The gastric microbiota richness index (observed OTUs, Chao) was significantly lower in CAG patients than in nCAG patients (P <0.05). Compared with avirulent Hp-II infection, virulent Hp-I infection significantly decreased the Shannon index in CAG patients (P <0.05). In nCAG patients, Hp-I infected patients had lower abundances of several dominant gastric bacteria (Aliidiomarina, Reyranella, Halomonas, Pseudomonas, Acidovorax) than Hp-II infected patients. Meanwhile, in CAG patients, Hp-I infected patients occupied lower abundances of several dominant oral bacteria (Neisseria, Staphylococcus and Haemophilus) than Hp-II infected patients. In addition, bile reflux significantly promoted the colonization of dominant oral microbiota (Veillonella, Prevotella 7 and Rothia) in the stomach of CAG patients. There was no significant symbiotic relationship between Helicobacter bacteria and non-Helicobacter bacteria in the stomach of nCAG patients, while Helicobacter bacteria distinctly linked with the non-Helicobacter bacteria (Pseudolabrys, Ralstonia, Bradyrhizobium, Mesorhizobium and Variovorax) in CAG patients.ConclusionsVirulent Hp infection alters the gastric microbiota, reduces microbial diversity, and enhances the symbiotic relationship between the Helicobacter bacteria and non-Helicobacter bacteria in patients with chronic gastritis. The data provides new evidence for treating Hp infection by improving the gastric microbiota.

Project description:Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancer-related genes. H. pylori infection is largely acquired during childhood, persisting long-term in about half of infected individuals, a subset of whom will go on to develop peptic ulcer disease and eventually gastric cancer, however, the sequence of events leading to disease is not completely understood. Knowledge on carcinogenesis and gastric damage-related biomarkers is abundant in adult populations, but scarce in children. We performed an extensive literature review focusing on gastric cancer related biomarkers identified in adult populations, which have been detected in children infected with H. pylori. Biomarkers were related to expression levels (RNA or protein) and/or methylation levels (DNA) in gastric tissue or blood of infected children as compared to non-infected controls. In this review, we identified 37 biomarkers of which 24 are over expressed, three are under expressed, and ten genes are significantly hypermethylated in H. pylori-infected children compared to healthy controls in at least 1 study. Only four of these biomarkers (pepsinogen I, pepsinogen II, gastrin, and SLC5A8) have been studied in asymptomatically infected children. Importantly, 13 of these biomarkers (β-catenin, C-MYC, GATA-4, DAPK1, CXCL13, DC-SIGN, TIMP3, EGFR, GRIN2B, PIM2, SLC5A8, CDH1, and VCAM-1.) are consistently deregulated in infected children and in adults with gastric cancer. Future studies should be designed to determine the clinical significance of these changes in infection-associated biomarkers in children and their persistence over time. The effect of eradication therapy over these biomarkers in children if proven significant, could lead to modifications in treatment guidelines for younger populations, and eventually promote the development of preventive strategies, such as vaccination, in the near future.

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Helicobacter pylori infection is associated with an altered gastric microbiota in children.

Publications

Helicobacter pylori infection is associated with an altered gastric microbiota in children.

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