Unravelling the metabolic and immunological impacts of helicobacter pylori eradication in healthy adult/youth through omics / Theresa Yap Wan Chen
Helicobacter pylori is an important bacterial aetiological agent of gastroduodenal diseases. H. pylori positivity is also a risk factor for gastric adenocarcinoma and MALT lymphoma. Ironically, accumulating evidence demonstrates that H. pylori may protect the human host against obesity and atopi...
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| Format: | Thesis |
| Published: |
2017
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| Online Access: | http://studentsrepo.um.edu.my/7844/7/wan_chen.pdf http://studentsrepo.um.edu.my/7844/ |
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| Summary: | Helicobacter pylori is an important bacterial aetiological agent of gastroduodenal diseases. H. pylori positivity is also a risk factor for gastric adenocarcinoma and MALT
lymphoma. Ironically, accumulating evidence demonstrates that H. pylori may protect
the human host against obesity and atopic disorders. We hypothesised that
disappearance H. pylori leads to changes in the human gut microbiome resulting in local
and systemic changes in metabolism that may contribute to eventual development of
undesirable metabolic and immunological disorders. This study was therefore, carried
out to investigate the implications of H. pylori eradication and the association with
metabolic and immunological disorders in a young healthy adult population. From 573
healthy adult volunteers (18-30 years-old) screened, the prevalence of H. pylori
infection was 9.9%. Eventually, 29 H. pylori-positive subjects were enrolled and
assessed during baseline followed by 6, 12 and 18 months post-H. pylori eradication.
Faecal metagenomics and lipidomics were used to evaluate the local effects following H.
pylori eradication on the gut microbiota and further metabolic, immunological and
plasma metabolomic studies were performed to reflect the systemic effects of H. pylori
eradication. The impact of H. pylori on the human gut microbiome pre- and post
eradication was investigated using 16S rRNA gene (V3-V4 region) sequencing and data
analysis using Qiime pipeline. The local and systemic effects of H. pylori, post
eradication, were examined through untargeted faecal lipidomics and plasma
metabolomics using liquid chromatography mass spectrometry (LC-MS). The effect
of H. pylori eradication on meal-associated changes on gastrointestinal metabolic
hormones, cytokines and Immunolglobulin E (IgE) antibody level were evaluated using
a multiplex bead assay and enzyme-linked immunosorbent assay, correspondingly. The
microbial diversity was found to be similar pre- and post-H. pylori eradication with no
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significant differences in bacterial richness and evenness. Despite that, some changes in
the bacterial communities at the phylum and genus levels were notable, particularly the
decrease in relative abundance of Bacterioidetes and the corresponding increase in
Firmicutes following 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. Faecal lipidomics and plasma metabolomics revealed that
eradication of H. pylori dramatically changed many global metabolite/lipid features,
with the majority of them being down-regulated. The influence of gut microbiota on
plasma metabolites profile was also demonstrated. These findings primarily implicate
the perturbation of gut microbiota following H. pylori eradication in host energy and
lipid metabolism which may eventually lead to the development of metabolic disorders.
Metabolic studies demonstrated that H. pylori eradication was associated with long-term
disturbance in active amylin, pancreatic polypeptide and total peptide YY both pre- and
post-prandially and glucagon-like peptide-1 post-prandially (p<0.05). An inverse
association between H. pylori infection and allergen specific-IgE antibodies (p<0.05)
was observed. The predictive metabolic signature of metabolic and immunological
disorders following H. pylori eradication may give us insights on complex interaction of
H. pylori with gut microbiota, the importance of biosis of the gut microbiota and their implications in human health. In conclusion, eradication of H. pylori demonstrated intricate and complex interactions between H. pylori and the gut microbiota in modulating human health and therefore, a point to ponder upon future management of H. pylori infection. |
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