Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora

Abstract The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant c...

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Main Authors: Christina Almarmouri, Mohammed I. El-Gamal, Mohamed Haider, Mohamad Hamad, Shamsul Qumar, Merylin Sebastian, Rose Ghemrawi, Jibran Sualeh Muhammad, Christophe Burucoa, Ghalia Khoder
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Gut Pathogens
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Online Access:https://doi.org/10.1186/s13099-025-00708-1
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author Christina Almarmouri
Mohammed I. El-Gamal
Mohamed Haider
Mohamad Hamad
Shamsul Qumar
Merylin Sebastian
Rose Ghemrawi
Jibran Sualeh Muhammad
Christophe Burucoa
Ghalia Khoder
author_facet Christina Almarmouri
Mohammed I. El-Gamal
Mohamed Haider
Mohamad Hamad
Shamsul Qumar
Merylin Sebastian
Rose Ghemrawi
Jibran Sualeh Muhammad
Christophe Burucoa
Ghalia Khoder
author_sort Christina Almarmouri
collection DOAJ
description Abstract The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant challenges, such as increasing antibiotic resistance, high recurrence rates, and adverse effects such as gut microflora dysbiosis. These limitations have driven the exploration of alternative antibiotic-free therapies, including the use of plant-based compounds, probiotics, nanoparticles, phage therapy, antimicrobial peptides, and H. pylori vaccines. Among these, urease-targeted therapy has shown particular promise. Urease enables the survival and colonization of H. pylori by neutralizing stomach acidity. Targeting this urease without disrupting beneficial gut microflora offers a selective mechanism to impair H. pylori, due to the absence of this enzyme in most of the human gut microbiome. In this review, we highlight advancements and limitations in the field of antibiotic-free therapies, with a particular focus on anti-urease strategies. We explore the structural and functional characteristics of urease, its role in H. pylori pathogenesis, and its potential as a therapeutic target. For the first time, we provide a comprehensive analysis of natural, semisynthetic, and synthetic anti-urease compounds, emphasizing their mechanisms of action, efficacy, and safety profiles. Advances in silico, in vitro, and in vivo studies have identified several promising anti-urease compounds with high specificity and minimal toxicity. By focusing on urease inhibition as a targeted strategy, this review underscores its potential to overcome antibiotic resistance while minimizing gut dysbiosis and improving the outcomes of H. pylori infection treatment. Graphical Abstract
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spelling doaj-art-f4be3b2e93a8422ebdf6f4ce7cdcaf0d2025-08-20T03:16:47ZengBMCGut Pathogens1757-47492025-05-0117113710.1186/s13099-025-00708-1Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microfloraChristina Almarmouri0Mohammed I. El-Gamal1Mohamed Haider2Mohamad Hamad3Shamsul Qumar4Merylin Sebastian5Rose Ghemrawi6Jibran Sualeh Muhammad7Christophe Burucoa8Ghalia Khoder9Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of SharjahResearch Institute for Medical & Health Sciences, University of SharjahDepartment of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of SharjahResearch Institute for Medical & Health Sciences, University of SharjahResearch Institute for Medical & Health Sciences, University of SharjahResearch Institute for Medical & Health Sciences, University of SharjahCollege of Pharmacy, Al Ain UniversityDepartment of Biomedical Sciences, College of Medicine and Health, University of BirminghamLaboratoire de Bactériologie, U1070 INSERM, CHU de Poitiers, Université de PoitiersDepartment of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of SharjahAbstract The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant challenges, such as increasing antibiotic resistance, high recurrence rates, and adverse effects such as gut microflora dysbiosis. These limitations have driven the exploration of alternative antibiotic-free therapies, including the use of plant-based compounds, probiotics, nanoparticles, phage therapy, antimicrobial peptides, and H. pylori vaccines. Among these, urease-targeted therapy has shown particular promise. Urease enables the survival and colonization of H. pylori by neutralizing stomach acidity. Targeting this urease without disrupting beneficial gut microflora offers a selective mechanism to impair H. pylori, due to the absence of this enzyme in most of the human gut microbiome. In this review, we highlight advancements and limitations in the field of antibiotic-free therapies, with a particular focus on anti-urease strategies. We explore the structural and functional characteristics of urease, its role in H. pylori pathogenesis, and its potential as a therapeutic target. For the first time, we provide a comprehensive analysis of natural, semisynthetic, and synthetic anti-urease compounds, emphasizing their mechanisms of action, efficacy, and safety profiles. Advances in silico, in vitro, and in vivo studies have identified several promising anti-urease compounds with high specificity and minimal toxicity. By focusing on urease inhibition as a targeted strategy, this review underscores its potential to overcome antibiotic resistance while minimizing gut dysbiosis and improving the outcomes of H. pylori infection treatment. Graphical Abstracthttps://doi.org/10.1186/s13099-025-00708-1H. pyloriUreaseAnti-urease compoundsAntibiotic resistanceGut microfloraAlternative antibiotic-free therapies
spellingShingle Christina Almarmouri
Mohammed I. El-Gamal
Mohamed Haider
Mohamad Hamad
Shamsul Qumar
Merylin Sebastian
Rose Ghemrawi
Jibran Sualeh Muhammad
Christophe Burucoa
Ghalia Khoder
Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
Gut Pathogens
H. pylori
Urease
Anti-urease compounds
Antibiotic resistance
Gut microflora
Alternative antibiotic-free therapies
title Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
title_full Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
title_fullStr Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
title_full_unstemmed Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
title_short Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora
title_sort anti urease therapy a targeted approach to mitigating antibiotic resistance in helicobacter pylori while preserving the gut microflora
topic H. pylori
Urease
Anti-urease compounds
Antibiotic resistance
Gut microflora
Alternative antibiotic-free therapies
url https://doi.org/10.1186/s13099-025-00708-1
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