INTRODUCTION: To evaluate the prescription patterns, effectiveness, and safety of adding probiotics to Helicobacter pylori eradication therapy, in Europe. METHODS: International, prospective, noninterventional registry of the clinical practice of the European gastroenterologists. Data were collected and quality reviewed until March 2021 at AEG-REDCap. The effectiveness was evaluated by modified intention-to-treat analysis, differentiating by geographic areas. Adverse events (AEs) were categorized as mild, moderate, and severe. RESULTS: Overall, 36,699 treatments were recorded, where 8,233 (22%) were prescribed with probiotics. Probiotics use was associated with higher effectiveness in the overall analysis (odds ratio [OR] 1.631, 95% confidence interval [CI] 1.456-1.828), as well as in triple (OR 1.702, 95% CI 1.403-2.065), quadruple (OR 1.383, 95% CI 0.996-1.920), bismuth quadruple (OR 1.248, 95% CI 1.003-1.554), and sequential therapies (OR 3.690, 95% CI 2.686-5.069). Lactobacillus genus was associated with a higher therapy effectiveness in Eastern Europe when triple (OR 2.625, 95% CI 1.911-3.606) and bismuth quadruple (OR 1.587, 95% CI 1.117-2.254) first-line therapies were prescribed. In Central Europe, the use of probiotics was associated with a decrease in both the overall incidence of AEs (OR 0.656, 95% CI 0.516-0.888) and severe AEs (OR 0.312, 95% CI 0.217-0.449). Bifidobacterium genus was associated with lower overall (OR 0.725, 95% CI 0.592-0.888) and severe (OR 0.254, 95% CI 0.185-0.347) AEs, and Saccharomyces was associated with reduced overall (OR 0.54, 95% CI 0.32-0.91) and severe (OR 0.257, 95% CI 0.123-0.536) AEs under quadruple-bismuth regimen. DISCUSSION: In Europe, the use of probiotics was associated with higher effectiveness and safety of H. pylori eradication therapy. Lactobacillus improved treatment effectiveness, whereas Bifidobacterium and Saccharomyces were associated with a better safety profile.

2nd Department of Internal Medicine Gastroenterology and Geriatrics University Hospital Olomouc Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czech Republic

Center for Research in Health Technologies and Information Systems Porto Portugal

CIBERehd Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Madrid Spain

CIBERehd Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas Madrid Spain

CIBERehd Zaragoza Spain

Clinic of Gastroenterology and Hepatology Clinical Center of Serbia Belgrade Serbia

Department of Gastroenterology A S Loginov Moscow Clinical Scientific Center Moscow Russia

Department of Gastroenterology and Digestive Endoscopy Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Gastroenterology Biodonostia Health Research Institute San Sebastián Spain

Department of Gastroenterology DC Rogaska Slatina Slovenia

Department of Gastroenterology Digestive Diseases Centre Riga Latvia

Department of Gastroenterology Hepatology and Infectious Diseases University Hospital of Magdeburg Magdeburg Germany

Department of Gastroenterology Hospital Clínico de Valladolid Valladolid Spain

Department of Gastroenterology Hospital General de Tomelloso Tomelloso Spain

Department of Gastroenterology Hospital General Universitario de Valencia Valencia Spain

Department of Gastroenterology Hospital Universitario de Valme Seville Spain

Department of Gastroenterology Hospital Universitario Miguel Servet Zaragoza Spain

Department of Gastroenterology Interni Oddelek Diagnostic Centre Bled Slovenia

Department of Gastroenterology Østfold Hospital Trust Grålum Norway

Department of Gastroenterology University Hospital of Split Split Croatia

Department of Hospital Medicine Kazan State Medical University Kazan Russia

Department of Internal Medicine and Gastroenterology Azerbaijan State Advanced Training Institute for Doctors named by A Aliyev Baku Azerbaijan

Department of Medical and Surgical Sciences Sant'Orsola Malpighi University Hospital Bologna Italy

Department of Medical Microbiology Medical University of Sofia Sofia Bulgaria

Department of Medicine Universidad del País Vasco San Sebastián Spain

Department of Outpatient Therapy and Family Medicine Tver State Medical University Tver Russia

Department of Pancreatic Biliary and Upper Digestive Tract Disorders A S Loginov Moscow Clinical Scientific Center Moscow Russia

Department of Propaedeutic of Internal Diseases and Gastroenterology Russian University of Medicine Moscow Russia

Department of Statistical Methods Faculty of Science Universidad de Zaragoza Zaragoza Spain

Department of Surgery University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

Departments the Division for the Study of the Digestive Diseases and Its Comorbidity With Noncommunicable Diseases Government Institution L T Malaya Therapy National Institute of NAMS of Ukraine Kharkiv Ukraine

Digestive Unit Agencia Sanitaria Costa del Sol Marbella Spain

Division of Gastroenterology Rabin Medical Center TelAviv Israel

Faculty of Medicine University of Belgrade Belgrade Serbia

Gastrocenter Perm Russia

Gastroenterology Clinic Henry Dunant Hospital Athens Greece

Gastroenterology Department Centro Hospitalar do Porto Porto Portugal

Gastroenterology Department Kantonsspital Aarau Aarau Switzerland

Gastroenterology Instituto de Investigación Sanitaria Princesa Madrid Spain

Gastroenterology Unit Hospital Santos Reyes Aranda de Duero Spain

Gastroenterology University of Oviedo Oviedo Spain

Gastrointestinal Oncology Endoscopy and Surgery Research Group Althaia Xarxa Assistencial Universitària de Manresa FP Manresa Spain

Hospital Clínic de Barcelona Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas University of Barcelona Barcelona Spain

INSERM U1312 BRIC Université de Bordeaux Bordeaux France

Institut de Recerca i Innovació en Ciències de la Vida i de la Salut de la Catalunya Central Vic Spain

Institute of Clinical and Preventive Medicine University of Latvia Riga Latvia

Instituto de Biocomputación y Física de Sistemas Complejos Universidad de Zaragoza Zaragoza Spain

Instituto De Ciências Biomédicas de Abel Salazar Universidade do Porto Porto Portugal

Instituto de Investigación Sanitaria de Aragón Zaragoza Spain

Medicina interna e Gastroenterologia Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Redes de Investigación Cooperativa Orientada a Resultados en Salud Marbella Spain

Research and Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

School of Medicine Faculty of Health Sciences Trinity College Dublin Dublin Ireland

Servicio de Aparato Digestivo Hospital Clínico Universitario Lozano Blesa Zaragoza Spain

Servicio de Aparato Digestivo Hospital Universitario de La Princesa Instituto de Investigación Sanitaria Princesa Madrid Spain

Tel Aviv University TelAviv Israel

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Cho J, Prashar A, Jones NL, et al. Helicobacter pylori infection. Gastroenterol Clin North Am 2021;50(2):261–82.

Malfertheiner P, Megraud F, Rokkas T, et al.; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report. Gut 2022;71(9):1724–62.

Megraud F, Bruyndonckx R, Coenen S, et al.; European Helicobacter pylori Antimicrobial Susceptibility Testing Working Group. Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community. Gut 2021;70(10):1815–22.

Cummings LC, Hojat LS, Nguyen DC, et al. Tailored treatment based on Helicobacter pylori genetic markers of resistance is associated with higher eradication success. Am J Gastroenterol 2023;118(2):360–3.

Caldas M, Pérez-Aisa Á, Tepes B, et al. The role of statins on Helicobacter pylori eradication: Results from the European Registry on the Management of H. pylori (Hp-EuReg). Antibiotics (Basel) 2021;10(8):965.

Simadibrata DM, Syam AF, Lee YY. A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022;37(12):2217–28.

Nyssen OP, Perez-Aisa A, Tepes B, et al. Adverse event profile during the treatment of Helicobacter pylori : A real-world experience of 22,000 patients from the European Registry on H. pylori Management (Hp-EuReg). Am J Gastroenterol 2021;116(6):1220–9.

Chen L, Xu W, Lee A, et al. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial. EBioMedicine 2018;35:87–96.

Losurdo G, Cubisino R, Barone M, et al. Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis. World J Gastroenterol 2018;24(1):139–49.

Shi X, Zhang J, Mo L, et al. Efficacy and safety of probiotics in eradicating Helicobacter pylori : A network meta-analysis. Medicine (Baltimore) 2019;98(15):e15180.

Aumpan N, Mahachai V, Vilaichone RK. Management of Helicobacter pylori infection. JGH Open 2023;7(1):3–15.

McNicholl AG, O'Morain CA, Megraud F, et al., As Scientific Committee of the Hp-Eureg on Behalf of the National Coordinators. Protocol of the European Registry on the management of Helicobacter pylori infection (Hp-EuReg). Helicobacter 2019;24(5):e12630.

Kirchheiner J, Glatt S, Fuhr U, et al. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol 2009;65(1):19–31.

Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2018;16(6):800–8.e7.

Nafria B, Nyssen OP, Bujanda L, et al. Prevalence of primary clarithromycin resistance in patients infected with helicobacter pylori in Europe in the last four decades [UEGweek abstract PP0257]. United European Gastroenterol J 2024;12(Suppl):S8.

Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: A systematic review and meta-analysis in World Health Organization regions. Gastroenterology 2018;155(5):1372–82.e17.

Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology 2017;153(2):420–9.

Li Y, Choi H, Leung K, et al. Global prevalence of Helicobacter pylori infection between 1980 and 2022: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2023;8(6):553–64.

Nyssen OP, Bordin D, Tepes B, et al.; Hp-EuReg Investigators. European Registry on Helicobacter pylori management (Hp-EuReg): Patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21‚Äâ533 patients. Gut 2021;70(1):40–54.

Ji YH, Shi YM, Hei QW, et al. Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection. Helicobacter 2023;28(1):e12937.

Zhou L, Lu H, Song Z, et al.; on behalf of Helicobacter Pylori Study Group of Chinese Society of Gastroenterology. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl) 2022;135(24):2899–910.

Fernández-Alonso M, Aguirre Camorlinga A, Messiah SE, et al. Effect of adding probiotics to an antibiotic intervention on the human gut microbial diversity and composition: A systematic review. J Med Microbiol 2022;71(11):e001625.

Wieërs G, Belkhir L, Enaud R, et al. How probiotics affect the microbiota. Front Cell Infect Microbiol 2019;9:454.

Suez J, Zmora N, Segal E, et al. The pros, cons, and many unknowns of probiotics. Nat Med 2019;25(5):716–29.

Caballero-Flores G, Pickard JM, Núñez G. Microbiota-mediated colonization resistance: Mechanisms and regulation. Nat Rev Microbiol 2023;21(6):347–60.

Ferrer M, Méndez-García C, Rojo D, et al. Antibiotic use and microbiome function. Biochem Pharmacol 2017;134:114–26.

Coconnier MH, Lievin V, Hemery E, et al. Antagonistic activity against Helicobacter infection in vitro and in vivo by the human Lactobacillus acidophilus strain LB. Appl Environ Microbiol 1998;64(11):4573–80.

Keikha M, Karbalaei M. Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections. BMC Gastroenterol 2021;21(1):388.

Penumetcha SS, Ahluwalia S, Irfan R, et al. The efficacy of probiotics in the management of Helicobacter pylori : A systematic review. Cureus 2021;13(12):e20483.

Gotteland M, Brunser O, Cruchet S. Systematic review: Are probiotics useful in controlling gastric colonization by Helicobacter pylori ? Aliment Pharmacol Ther 2006;23(8):1077–86.

Emara MH, Elhawari SA, Yousef S, et al. Emerging role of probiotics in the management of Helicobacter pylori infection: Histopathologic perspectives. Helicobacter 2016;21(1):3–10.

Bai X, Zhu M, He Y, et al. The impacts of probiotics in eradication therapy of Helicobacter pylori . Arch Microbiol 2022;204(12):692.

Oh B, Kim BS, Kim JW, et al. The effect of probiotics on gut microbiota during the Helicobacter pylori eradication: Randomized controlled trial. Helicobacter 2016;21(3):165–74.

Lau CS, Ward A, Chamberlain RS. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori : A meta-analysis. Infect Drug Resist 2016;9:275–89.

He XJ, Wang XL, Sun DJ, et al. The efficacy and safety of Saccharomyces boulardii in addition to antofloxacin-based bismuth quadruple therapy for Helicobacter pylori eradication: A single-center, prospective randomized-control study. Therap Adv Gastroenterol 2023;16:17562848221147763.

McFarland LV, Huang Y, Wang L, et al. Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events. United European Gastroenterol J 2016;4(4):546–61.

Moreno Márquez C, Fernández Álvarez P, Valdés Delgado T, et al. Randomized, double-blind, placebo-controlled clinical trial on the usefulness of probiotic Lactobacillus reuteri in bismuth-containing quadruple eradication therapy for infection with Helicobacter pylori . Rev Esp Enferm Dig 2022;114(2):89–95.

Viazis N, Argyriou K, Kotzampassi K, et al. A four-probiotics regimen combined with A standard Helicobacter pylori -eradication treatment reduces side effects and increases eradication rates. Nutrients 2022;14(3):632.

Ismail NI, Nawawi KNM, Hsin DCC, et al. Probiotic containing Lactobacillus reuteri DSM 17648 as an adjunct treatment for Helicobacter pylori infection: A randomized, double-blind, placebo-controlled trial. Helicobacter 2023;28(6):e13017.

Gisbert JP, McNicholl AG. Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. Helicobacter 2017;22(4):12392.

Wang F, Feng J, Chen P, et al. Probiotics in Helicobacter pylori eradication therapy: Systematic review and network meta-analysis. Clin Res Hepatol Gastroenterol 2017;41(4):466–75.

Éliás AJ, Barna V, Patoni C, et al. Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: A systematic review and meta-analysis. BMC Med 2023;21(1):262.

Rodenes-Gavidia A, Lamelas A, Bloor S, et al. An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: A single arm open label trial. Front Cell Infect Microbiol 2023;13:1240267.

Zhang M, Zhang C, Zhao J, et al. Meta-analysis of the efficacy of probiotic-supplemented therapy on the eradication of H. pylori and incidence of therapy-associated side effects. Microb Pathog 2020;147:104403.

Zhou BG, Chen LX, Li B, et al. Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: A systematic review and meta-analysis with trial sequential analysis. Helicobacter 2019;24(5):e12651.

Bujanda L, Nyssen OP, Vaira D, et al.; The Hp-EuReg Investigators. Antibiotic resistance prevalence and trends in patients infected with Helicobacter pylori in the period 2013–2020: Results of the European Registry on H. pylori Management (Hp-EuReg). Antibiotics (Basel) 2021;10(9):1058.

Zobrazit více v PubMed

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