scholarly journals 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

2017 ◽  
Author(s):  
Bryony N. Parsons ◽  
Umer Zeeshan Ijaz ◽  
Rosalinda D’Amore ◽  
Michael D. Burkitt ◽  
Richard Eccles ◽  
...  

ABSTRACTObjectiveSeveral 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.Design95 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).ResultsSamples 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.ConclusionAutoimmune 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.SIGNIFICANCE OF THIS STUDY1.What is already known about this subject?Some conditions which result in reduced gastric acid secretion and hypochlorhydria are associated with an increased risk of gastric tumourigenesis.This risk is different in patients with H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and chronic proton pump inhibitor use.Hypochlorhydria and H. pylori infection cause alterations in the composition of the gastric microbiota.2.What are the new findings?We used 16S rRNA sequencing to characterise the microbiota in gastric corpus biopsies from a well characterised cohort of patients.The gastric microbiota was different in patients who were hypochlorhydric as a result of H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.Biochemical pathways associated with gastric carcinogenesis such as the fumarate reductase pathway were predicted to be altered in patients with atrophic gastritis.3.How might it impact on clinical practice in the foreseeable future?Understanding how the microbiota that colonise the hypochlorhydric stomach influence gastric carcinogenesis may ultimately permit stratification of patients’ subsequent tumour risk.Interventions that alter the composition of the gastric microbiome in hypochlorhydric patients with atrophic gastritis should be tested to investigate whether they alter the subsequent risk of developing gastric malignancy.

2021 ◽  
Author(s):  
Ombretta Repetto ◽  
Valli De Re ◽  
Paolo Giuffrida ◽  
Marco Vincenzo Lenti ◽  
Raffaella Magris ◽  
...  

Abstract Background Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC. Methods Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients. Results 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC). Conclusion This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Reuben Veysey-Smith ◽  
Andrew R. Moore ◽  
Senthil V. Murugesan ◽  
Laszlo Tiszlavicz ◽  
Graham J. Dockray ◽  
...  

BackgroundHypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood.Materials and MethodsFasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy. After exclusions, 982 patients were divided into four groups and their results analysed. We compared gastrin concentrations in normal patients (no H. pylori infection, no PPI use and no histological evidence of gastric preneoplasia (n=233)), with those in patients who were taking regular PPIs (H. pylori negative with no gastric preneoplasia (n=301)), patients who had active H. pylori infection but no gastric preneoplasia (n=164) and patients with histologically confirmed gastric preneoplasia (n=284).ResultsMedian fasting gastrin concentration in the normal group was 20pM and was significantly increased in PPI users (46pM, p&lt;0.0001), patients with active H. pylori infection (27pM, p&lt;0.0001), and patients with antral (25pM, p&lt;0.01) or corpus (48pM, p&lt;0.0001) gastric preneoplasia. PPI use resulted in further significant increases in fasting serum gastrin concentrations in patients who were infected with H. pylori (50pM, n=56) or who had antral gastric preneoplasia (53pM, n=87), but did not significantly alter serum gastrin concentrations in patients with corpus preneoplasia (90pM, n=66).ConclusionsPPI use, H. pylori infection and atrophic gastritis all caused significant elevations of median fasting gastrin concentrations. However, several patients who had potential risk factors for hypergastrinaemia still demonstrated fasting serum gastrin concentrations within the normal range.


2021 ◽  
Vol 11 ◽  
Author(s):  
Cheol Min Shin ◽  
Nayoung Kim ◽  
Ji Hyun Park ◽  
Dong Ho Lee

Helicobacter pylori infection changes gastric microbiota profiles. However, it is not clear whether H. pylori eradication can restore the healthy gastric microbiota. Moreover, there has been no study regarding the changes in gastric microbiota with aging. The objective of this study was to investigate the changes in gastric corpus microbiota with age and following H. pylori eradication. Changes in corpus mucosa-associated microbiota were evaluated in 43 individuals with endoscopic follow-up &gt; 1 year, including 8 H. pylori-uninfected and 15 H. pylori-infected subjects with no atrophy/metaplasia by histology and pepsinogen I/II ratio &gt; 4.0; 17 H. pylori-infected subjects with atrophy/metaplasia and pepsinogen I/II ratio &lt; 2.5; and 3 subjects with atrophy/metaplasia, no evidence of active H. pylori infection, negative for anti-H. pylori immunoglobulin G (IgG) antibody testing, and no previous history of H. pylori eradication. Successful H. pylori eradication was achieved in 21 patients. The gastric microbiota was characterized using an Illumina MiSeq platform targeting 16S ribosomal DNA (rDNA). The mean follow-up duration was 57.4 months (range, 12–145 months), and median follow-up visit was 1 (range, 1–3). Relative abundance of Lactobacillales and Streptococcus was increased with atrophy/metaplasia. In H. pylori-uninfected subjects (n = 8), an increase in Proteobacteria (Enhydrobacter, Comamonadaceae, Sphingobium); a decrease in Firmicutes (Streptococcus, Veillonella), Fusobacteria (Fusobacterium), Nocardioidaceae, Rothia, and Prevotella; and a decrease in microbial diversity were observed during the follow-up (p trend &lt; 0.05). In 10 of 21 subjects (47.6%), H. pylori eradication induced restoration of microbial diversity; however, a predominance of Acinetobacter with a decrease in microbial diversity occurred in 11 subjects (52.3%). The presence of atrophy/metaplasia at baseline and higher neutrophil infiltration in the corpus were associated with the restoration of gastric microbiota after successful eradication, whereas a higher relative abundance of Acinetobacter at baseline was associated with the predominance of Acinetobacter after H. pylori eradication (p &lt; 0.05). To conclude, in H. pylori-uninfected stomach, relative abundance of Proteobacteria increases, relative abundance of Firmicutes and Fusobacteria decreases, and microbial diversity decreases with aging. H. pylori eradication does not always restore gastric microbiota; in some individuals, gastric colonization by Acinetobacter species occurs after anti-Helicobacter treatment.


2005 ◽  
Vol 19 (7) ◽  
pp. 399-408 ◽  
Author(s):  
Nicola L Jones ◽  
Philip Sherman ◽  
Carlo A Fallone ◽  
Nigel Flook ◽  
Fiona Smaill ◽  
...  

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H pylori infection; recurrent abdominal pain of childhood is not an indication to test for H pylori infection; H pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H pylori infection; serological antibody tests are not recommended as diagnostic tools for H pylori infection in children; first-line therapy for H pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H pylori infection in children is 14 days; and H pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.


2001 ◽  
Vol 56 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Fernando Marcuz Silva ◽  
Schlioma Zaterka ◽  
Jaime Natan Eisig ◽  
Ethel Zimberg Chehter ◽  
Décio Chinzon ◽  
...  

Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs) change the response to therapy. METHODS: Two hundred patients with peptic ulcer (upper endoscopy) and H. pylori infection (histology and rapid urease test - RUT) were included. A proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg), tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT. RESULTS: The eradication rate of H. pylori per protocol was 65% (128/196 patients). This rate was 53% for previously treated patients, rising to 76% for not previously treated patients, with a statistical difference p<0.01. No significant difference was observed regarding sex, tobacco use, alcohol consumption, and NSAID use, but for elderly patients the difference was p = 0.05. Adherence to treatment was good, and side effects were mild. CONCLUSIONS: A proton pump inhibitor, tinidazole, and clarithromycin bid for seven days resulted in H. pylori eradication in 65% of the patients. Previous treatments were the main cause of treatment failure.


2020 ◽  
pp. 205064062097261
Author(s):  
Olga P Nyssen ◽  
Angeles Perez-Aisa ◽  
Manuel Castro-Fernandez ◽  
Rinaldo Pellicano ◽  
Jose M. Huguet ◽  
...  

Background There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterología REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e. three capsules every 6 hours for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.


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