PMID- 29095917 OWN - NLM STAT- MEDLINE DCOM- 20171113 LR - 20220129 IS - 1553-7374 (Electronic) IS - 1553-7366 (Print) IS - 1553-7366 (Linking) VI - 13 IP - 11 DP - 2017 Nov TI - Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. PG - e1006653 LID - 10.1371/journal.ppat.1006653 [doi] LID - e1006653 AB - Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. FAU - Parsons, Bryony N AU - Parsons BN AUID- ORCID: 0000-0003-3599-1089 AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Ijaz, Umer Z AU - Ijaz UZ AUID- ORCID: 0000-0001-5780-8551 AD - Department of Infrastructure and Environment University of Glasgow, School of Engineering, Glasgow, UNITED KINGDOM. FAU - D'Amore, Rosalinda AU - D'Amore R AUID- ORCID: 0000-0002-2638-4466 AD - Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Burkitt, Michael D AU - Burkitt MD AUID- ORCID: 0000-0002-5055-6408 AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. AD - Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UNITED KINGDOM. FAU - Eccles, Richard AU - Eccles R AD - Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Lenzi, Luca AU - Lenzi L AUID- ORCID: 0000-0003-2697-691X AD - Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Duckworth, Carrie A AU - Duckworth CA AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Moore, Andrew R AU - Moore AR AUID- ORCID: 0000-0001-7680-998X AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. AD - Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UNITED KINGDOM. FAU - Tiszlavicz, Laszlo AU - Tiszlavicz L AUID- ORCID: 0000-0003-1134-6587 AD - Department of Pathology, University of Szeged, Szeged, HUNGARY. FAU - Varro, Andrea AU - Varro A AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. FAU - Hall, Neil AU - Hall N AUID- ORCID: 0000-0003-2808-0009 AD - Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UNITED KINGDOM. AD - The Earlham Institute, Norwich Research Park, Norwich, UNITED KINGDOM. AD - School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, Norfolk, UNITED KINGDOM. FAU - Pritchard, D Mark AU - Pritchard DM AUID- ORCID: 0000-0001-7971-3561 AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UNITED KINGDOM. AD - Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UNITED KINGDOM. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 12-1028/AICR_/Worldwide Cancer Research/United Kingdom GR - G0900753/MRC_/Medical Research Council/United Kingdom GR - MR/K002279/1/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article DEP - 20171102 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 0 (Proton Pump Inhibitors) SB - IM MH - Achlorhydria/chemically induced/etiology/immunology/*microbiology MH - Adult MH - Aged MH - Autoimmune Diseases/drug therapy/immunology/microbiology MH - Cluster Analysis MH - Cohort Studies MH - England/epidemiology MH - Female MH - Gastric Mucosa/drug effects/immunology/*microbiology MH - Gastritis, Atrophic/drug therapy/immunology/microbiology MH - *Gastrointestinal Microbiome/drug effects MH - Helicobacter Infections/drug therapy/immunology/microbiology MH - Helicobacter pylori/drug effects/growth & development/immunology/isolation & purification MH - Hospitals, University MH - Humans MH - Male MH - Middle Aged MH - Proton Pump Inhibitors/adverse effects/therapeutic use MH - Risk MH - Stomach Neoplasms/epidemiology PMC - PMC5667734 COIS- The authors have declared that no competing interests exist. EDAT- 2017/11/03 06:00 MHDA- 2017/11/14 06:00 PMCR- 2017/11/02 CRDT- 2017/11/03 06:00 PHST- 2017/06/16 00:00 [received] PHST- 2017/09/18 00:00 [accepted] PHST- 2017/11/03 06:00 [entrez] PHST- 2017/11/03 06:00 [pubmed] PHST- 2017/11/14 06:00 [medline] PHST- 2017/11/02 00:00 [pmc-release] AID - PPATHOGENS-D-17-01295 [pii] AID - 10.1371/journal.ppat.1006653 [doi] PST - epublish SO - PLoS Pathog. 2017 Nov 2;13(11):e1006653. doi: 10.1371/journal.ppat.1006653. eCollection 2017 Nov.