Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

Abstract

BackgroundAccumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.MethodsAs part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.ResultsWe compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders.ConclusionsOur preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori Eradication

“…The up-regulation of Lipid A 12 and 18 months post- H. pylori eradication could probably be associated with the perturbation of microbiota in the gut following H. pylori eradication. In our previous fecal metagenomics study, we found a transient loss of H. pylori instantaneously following H. pylori eradication but reappeared at 12–18 months (Yap et al, 2016). Due to the overlapping time points, it is likely that H. pylori employs the advantage of ecological niche to replicate intracellularly and survive the anti-bacterial treatment (Yap et al, 2016).…”

“…Lipid A, one of the three structural components of the lipopolysaccharide (LPS) causes the pathophysiological effects associated with Gram-negative bacteria infections (Lodowska et al, 2007). Gram-negative bacteria such as Bacteroidetes and Proteobacteria (including H. pylori ) are dominant microorganisms in the gut (Ley et al, 2005; Yap et al, 2016). The up-regulation of Lipid A 12 and 18 months post- H. pylori eradication could probably be associated with the perturbation of microbiota in the gut following H. pylori eradication.…”

“…However, H. pylori is gradually disappearing from the human indigenous microbiota due to development of socioeconomic, modern hygienic practices and advent of antibiotics. There is an growing epidemiological and experimental evidences on the protective effects of H. pylori against the development of obesity (Nwokolo et al, 2003; Osawa, 2008; Francois et al, 2011; Yap et al, 2015, 2016), childhood asthma (Chen and Blaser, 2008), allergies (Amberbir et al, 2011), inflammatory bowel diseases (Amnon and Robert, 2012), in which the development of these diseases coincide with transient dysbiosis. However, the underlying protective mechanism of H. pylori against the development of these metabolic and immunological disorders is still not well-established.…”

“…We hypothesized that eradication of H. pylori (loss of H. pylori and/or H. pylori eradication therapy) may have undesirable implications on metabolic and immunological disorders. Our earlier studies indicate that H. pylori eradication could result in perturbation of gut microbiome (Yap et al, 2016) and homeostasis of human metabolic hormones involved in appetite-control and energy metabolism (Yap et al, 2015). This may eventually lead to the development of metabolic disorders.…”

Association of Helicobacter pylori and Crohn’s Disease Incidence: An Inversion Reaction?

“…Interestingly in this context, the microbiota in the upper gastrointestinal tract differ between H. pylori positive and negative individuals, possibly due to the observation that H. pylori infection increases gastric pH [9]. Another recent study reported that the microbiota also changed after eradication of H. pylori [10]. As the gastrointestinal microbiota is believed to substantially contribute to Crohn's disease development, a change in the In an ecological study, Helicobacter pylori and Crohn's disease are inversely correlated…”