Objective A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). Methods 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. Results Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. Conclusion Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

https://gut.bmj.com/content/gutjnl/69/12/2093.full.pdf

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus

Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance — single drug resistance, multidrug resistance and heteroresistance — seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens. Increasing levels of antibiotic resistance in Helicobacter pylori are a serious threat to human health globally. This Review discusses H. pylori infection and antibiotic resistance, and provides insights into the underlying mechanisms and clinical implications (including detection and management).

Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications.

Summary Background In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4–86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7–88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6–92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters. Methods This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov , NCT01906879 . Findings Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p Interpretation Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy. Funding National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial.

Parkinson's disease is a common neurodegenerative disorder that presents with nonmotor and motor symptoms. The nonmotor manifestations of Parkinson's disease often begin years before the motor symptoms. Autopsy studies, including both Parkinson's disease patients and matched controls, demonstrated that α-synuclein aggregates in Parkinson's disease patients can be found in both the substantia nigra and the enteric nervous system. Therefore, it has been hypothesized that the pathological process that leads eventually to Parkinson's disease might initially take place in the enteric nervous system years before the appearance of motor features. The gut microbiome plays essential roles in the development and maintenance of different body systems. Dysbiosis of the normal gut microbiome is thought to be associated with pathophysiologic changes not only in the gastrointestinal system itself but also in the enteric and central nervous systems. These changes are thought to ultimately cause loss of dopaminergic neurons via various mechanisms including the release of neurotoxins into the systemic circulation, decreased production of neuroprotective factors, and triggering inflammatory and autoimmune responses. In this review, we review the gut microbiome changes in Parkinson's disease and discuss the mechanisms by which gut microbiome dysbiosis may be a contributing factor to the pathophysiology of Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.

Implications of the Gut Microbiome in Parkinson's Disease.

The late 1800s Louis Pasteur and Robert Koch introduced and popularized the germ theory of disease. At that time, gastric cancer was the most common cause of cancer deaths in most countries making the stomach an early site of microbial research with a focus on gastric luminal and mucosal bacteria and the role of Boas-Oppler bacillus (Lactobacillus) in the diagnosis of gastric cancer. In the 1970s, the research focus evolved to studies of the gastric microbiome in the production of nitrosamines and included development of the Correa cascade. Interest in nitrosamine production peaked in the late 1980s and was replaced by studies of the newly described Helicobacter pylori and studies of its role in gastritis, gastric atrophy, and gastric cancer. The last decade has witnessed a rebirth in interest in the gastric microbiota as part of worldwide interest in the human microbiome. Although fungi were prominent in the studies of gastric microbiology in the nineteenth century, their potential role in disease pathogenesis has yet to be addressed using modern techniques. Overall, current studies of the gastric bacterial microbiome do not provide convincing evidence to expand the role of the gastric microbiome in cancer pathogenesis beyond what is directly attributable to the oncogenic potential of H. pylori and its role in persisting acute-on-chronic inflammation.

Microbiome and Gastric Cancer

The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.

To evaluate potency and safety of 14-day bismuth–furazolidone quadruple regimens and to compare efficacies of five proton pump inhibitors (PPIs) for the initial eradication of Helicobacter pylori (H. pylori), 175 eligible patients were enrolled and randomly assigned to 14-day quadruple regimens consisting of bismuth (400 mg), amoxicillin (1 g), furazolidone (100 mg), and a PPI, twice a day. PPIs used were Group A (pantoprazole capsules, 40 mg), Group B (pantoprazole tablets, 40 mg), Group C (lansoprazole, 30 mg), Group D (esomeprazole, 20 mg), and Group E (rabeprazole, 10 mg). H. pylori status was reassessed by 13C urea breath test on day 56 as the primary outcome. Gastrointestinal symptoms, parenteral side effects, compliance, and stool type were recorded simultaneously. The total eradication rates were 86.9% (152/175 [95% CI 80.9–91.5%]) and 95.6% (152/159 [91.1–98.2%]) by intention-to-treat (ITT) and per-protocol (PP) analysis. The efficacies of Group A, B, C, D, and E by ITT analysis were 91.4% (32/35 [76.9–98.2%]), 85.7% (30/35 [69.7–95.2%]), 88.6% (31/35 [73.3–96.8%]), 85.7% (30/35 [69.7–95.2%]), and 82.9% (29/35 [66.4–93.4%]) (p > 0.05). In the PP analysis, the efficacies were 97.0% (32/33), 93.8% (30/32), 93.9% (31/33), 100% (30/30), and 93.5% (29/31) (p > 0.05). Gastrointestinal symptoms and stool type were improved significantly (p < 0.05). Total side effects rate and poor compliance rate were 15.7% (25/159) and 5.0% (8/159). Fourteen-day bismuth–furazolidone quadruple regimens are of high potency and safety for the initial eradication of H. pylori. Efficacies of different PPIs and different dosages (9–32 mg omeprazole equivalents) showed no significant difference. The appropriate PPI can thus be chosen by clinicians.

Efficacies of different proton pump inhibitor-based 14-day bismuth–furazolidone quadruple regimens for the initial eradication of Helicobacter pylori in the southeast coastal region of China: an open-label, randomized clinical trial

Yujia Chen

Papers

The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.

Efficacies of different proton pump inhibitor-based 14-day bismuth–furazolidone quadruple regimens for the initial eradication of Helicobacter pylori in the southeast coastal region of China: an open-label, randomized clinical trial