Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Comparative maintenance performance of all biologic agents and small molecules in ulcerative colitis: a network meta-analysis.

BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30 mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2 mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10 mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10 mg/day and infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

H. Pylori Treatment in the COVID-19 Era. What Have We Learned So Far?

PURPOSE OF REVIEW: CoronaVirus Disease of 2019 (COVID-19) has negatively influenced the management of multiple conditions in regards to the gastroenterology patient. An equivalent change in the management of Helicobacter pylori (H. pylori)-related diseases was reported, as practically no eradication treatment was offered during most of the pandemic. Given the scarcity of published data, we performed a literature review trying to elucidate the effect of COVID-19 on H. pylori treatment. RECENT FINDINGS: COVID-19 has produced more questions than answers as to the outcome of COVID-19 in H. Pylori infected patients, post-COVID-19 patients treated for H. pylori, acid suppression and COVID-19 incidence and outcomes, and H. pylori eradication treatment in patients having recovered from COVID-19. We strongly believe that this scientific uncertainty produced by the COVID-19 pandemic has set up the stage for an incremental change in H. pylori treatment as COVID-19 has offered us the chance to speed up how we will, in the near future, approach patients with a possible Η. pylori infection.

Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Advances in the pharmacological and regulatory management of multidrug resistant Helicobacter pylori.

INTRODUCTION: Antibiotic resistance of Helicobacter pylori (H. pylori) hampers the success of eradication and in recent years multidrug resistance (MDR) shows an increase worldwide. AREAS COVERED: This review covers current aspects of pharmacological and regulatory management of MDR-resistant H. pylori infection. EXPERT OPINION: MDR H. pylori is increasing worldwide and its prevalence varies both between continents and countries. High consumption and misuse of antibiotics, H. pylori treatment failures and bacterial factors such as mutations, efflux pumps and biofilms are among the factors associated with MDR. Important steps for confronting the rise of MDR H. pylori strains should follow the principles of antibiotic stewardship, i.e. eradication regimens should be optimized with regard to all aspects of therapy, including drugs, doses, formulation, frequency of administration, administration in relation to meals and duration of therapy that reliably achieve at least 90% (preferably >95%) cure rates in adherent patients with susceptible infections.

Comparison of the management of Helicobacter pylori infection between the older and younger European populations.

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Helicobacter pylori Diagnostic Tests Used in Europe: Results of over 34,000 Patients from the European Registry on Helicobacter pylori Management.

BACKGROUND AND AIMS: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. METHODS: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. RESULTS: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. CONCLUSION: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.

Mucin Expression in the Small Bowel of Celiac Disease: A Systematic Review.

BACKGROUND: Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis, expression, and secretion may be a primary event or may be secondary to inflammation and carcinogenesis. OBJECTIVES: To assess current knowledge of mucin expression in the small bowel of celiac disease (CD) patients and to determine possible associations between mucin profile and gluten-free diet. METHODS: Medical literature searches of articles in English were conducted using the terms mucin and celiac. Observational studies were included. Pooled odds ratios and 95% confidence intervals were calculated. RESULTS: Of 31 articles initially generated by a literature search, 4 observational studies that fulfilled the inclusion criteria remained eligible for meta-analysis. These studies included 182 patients and 148 controls from four countries (Finland, Japan, Sweden, United States). Mucin expression was significantly increased in small bowel mucosa of CD patients than in normal small bowel mucosa (odds ratio [OR] 7.974, 95% confidence interval [95%CI] (1.599-39.763), P = 0.011] (random-effect model). Heterogeneity was significant: Q = 35.743, df (Q) = 7, P < 0.0001, I2 = 80.416%. ORs for MUC2 and MUC5AC expression in the small bowel mucosa of untreated CD patients were 8.837, 95%CI 0.222-352.283, P = 0.247 and 21.429, 95%CI 3.883-118.255, P < 0.0001, respectively. CONCLUSIONS: Expression of certain mucin genes in the small bowel mucosa of CD patients is increased and may serve as a diagnostic tool and assist in surveillance programs.

Current role of narrow band imaging in diagnosing gastric intestinal metaplasia: a systematic review and meta-analysis of its diagnostic accuracy.

Background: Gastric intestinal metaplasia (GIM) can be missed by random gastric biopsies taken during white light endoscopy. Narrow band imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking and the diagnostic accuracy of NBI in detecting GIM needs to be more precisely defined. The aim of this systematic review and meta-analysis was to study the diagnostic performance of NBI in detecting GIM. Methods: PubMed/Medline and EMBASE were screened for studies examining GIM in relation to NBI. Data from each study were extracted and calculations of pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratios (DORs), and areas under the curve (AUCs) were performed. Fixed or random effects models, were used as appropriate, depending on the presence of significant heterogeneity. Results: We included 11 eligible studies in the meta-analysis, comprising 1672 patients. NBI showed a pooled sensitivity of 80% (95% confidence interval [CI] 69-87), specificity of 93% (95%CI 85-97), DOR 48 (95%CI 20-121), and AUC of 0.93 (95%CI 0.91-0.95) in detecting GIM. Conclusions: This meta-analysis showed that NBI is a reliable endoscopic means of detecting GIM. NBI with magnification performed better than NBI without magnification. However, better designed prospective studies are needed to precisely determine the diagnostic role of NBI, especially in high-risk populations where early detection of GIM can impact gastric cancer prevention and survival.

Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review.

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference -1.16 (-1.50, -0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

How widespread and convenient H. pylori susceptibility testing will result in pharmacological opportunities.

INTRODUCTION: Until recently, antimicrobial therapy for Helicobacter pylori infections was almost universally empirical and based on a combination of expert opinion and local effectiveness. However, the new requirement that all therapeutic regimens reliably achieve high cure rates, the introduction of potassium competitive acid blockers and the availability of susceptibility testing many pharmacological opportunities particularly since all current therapies will require optimization. The ability to rapidly and inexpensively obtain H. pylori susceptibility data using stool samples makes obtaining susceptibility data practical and allows using susceptibility-based therapy routinely for both treatment-naïve patient and treatment failures. AREAS COVERED: We searched the literature from 1990 to current to identify studies reporting the effect of susceptibility testing on H. pylori treatment. This review examines how widespread and convenient H. pylori susceptibility testing will result in pharmacological opportunities. . Many pharmacological opportunities will emanate from a renewal of efforts to develop, propagate, confirm, and update best practices based on local and regional susceptibility/resistance patterns. EXPERT OPINION: The ability to evaluate treatment decisions and outcomes in susceptible infections and reliably achieve high cure rates should foster precise tailoring of pharmacologic therapy and should achieve the goals of high cure rates while preventing antimicrobial misuse and extending the useful life of current antibiotics.

A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome.

BACKGROUND: Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS. AIM: We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS. METHODS: Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored. RESULTS: Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%). CONCLUSION: The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.

Current role of tailored therapy in treating Helicobacter pylori infections. A systematic review, meta-analysis and critical analysis.

BACKGROUND AND AIMS: Recent guidelines dictate that all Helicobacter pylori (H. pylori) infected subjects should receive curative therapy. The efficacy of empirical regimens for H. pylori eradication might decline with bacterial, drug, and host factors. The necessity of a tailored therapy still remains controversial. Here we provide a meta-analysis of the current status of susceptibility-based (tailored) therapy in which susceptibility-based therapies were compared to the currently accepted choice of empiric therapy. In this rapidly closing era, neither the susceptibility nor empiric therapies were routinely optimized, such that we report the outcome of comparisons on the efficacy of unoptimized tailored vs. locally preferred empiric treatments. METHODS: PubMed, Medline, and Embase databases were searched using suitable keywords. Individual and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity was calculated employing the Cochrane Q test and I2 values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed. RESULTS: Thirty-four studies were included with a total of 9613 patients. Tailored therapy proved superior to empiric treatment [OR 2.07 (95% CI 1.53-2.79)]. However, tailored therapy achieved eradication rates >90% in only 15 (44%) studies and >95% in only 6 (17.6%). CONCLUSIONS: Although tailored therapy performed better than empiric treatment, the lack of optimization of therapies failed to reliably achieve high cure rates (>90%). These results emphasize that H. pylori infection, like other infectious diseases, should utilize the principles of antimicrobial stewardship in relation to treatment guidance.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Helicobacter pylori, gastric microbiota and gastric cancer relationship: Unrolling the tangle.

Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.