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Yi M, Chen S, Yi X, Zhang F, Zhou X, Zeng M, Song H. Helicobacter pylori infection process: from the molecular world to clinical treatment. Front Microbiol 2025; 16:1541140. [PMID: 40083792 PMCID: PMC11903457 DOI: 10.3389/fmicb.2025.1541140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 02/10/2025] [Indexed: 03/16/2025] Open
Abstract
Helicobacter pylori is a gram-negative microaerophilic microorganism intricately associated with chronic gastrointestinal disorders and gastric cancer. H. pylori can cause various upper digestive tract diseases, including chronic gastritis, peptic ulcer, gastroesophageal reflux disease, and gastric cancer. The bacterium exhibits a variety of pathogenic mechanisms, including colonization, the expression of virulence factors, and the development of drug resistance. This article presents a comprehensive review of H. pylori pathogenesis, emphasizing recent research advancements concerning the cytotoxin-associated gene A, vacuolating cytotoxin, outer membrane proteins, and other virulence factors. Additionally, it examines the molecular mechanisms underlying drug resistance and evaluates the efficacy of conventional therapeutic approaches. Recently, researchers have attempted novel therapeutic regimens, including probiotics and Chinese medicine-assisted therapies, to enhance therapeutic effects. This article aimed to offer an overview of the academic community's comprehension of H. pylori infection and to highlight the current treatment options.
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Affiliation(s)
- Meijing Yi
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Silan Chen
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Xinying Yi
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Fan Zhang
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Xuan Zhou
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Meiyan Zeng
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Houpan Song
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
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Kountouras J, Zavos C, Papanikolaou IS, Doulberis M. Potential impact of Helicobacter pylori infection on primary-angle closure glaucoma and primary open-angle glaucoma pathophysiology. Neuroscience 2025; 567:271-272. [PMID: 39756607 DOI: 10.1016/j.neuroscience.2025.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 12/31/2024] [Accepted: 01/02/2025] [Indexed: 01/07/2025]
Affiliation(s)
- Jannis Kountouras
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Macedonia, Greece.
| | - Christos Zavos
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Macedonia, Greece
| | - Ioannis S Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Michael Doulberis
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Macedonia, Greece; Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland; Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland
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Kountouras J. A glimpse into Helicobacter pylori involvement in hepatic encephalopathy. Arab J Gastroenterol 2025; 26:141-142. [PMID: 39870566 DOI: 10.1016/j.ajg.2025.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/10/2025] [Indexed: 01/29/2025]
Affiliation(s)
- Jannis Kountouras
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Macedonia, Greece.
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Xu S, Feng Y, Li H, Huang H, Chen Q, Zhu B, Liu A, Xu Y, Jin X, Gui S, Lu X. Natural TPs inhibit biofilm formation by Multidrug-resistant Acinetobacter baumannii and biofilm-induced pulmonary inflammation. Microb Pathog 2025; 198:107172. [PMID: 39608508 DOI: 10.1016/j.micpath.2024.107172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 11/30/2024]
Abstract
Multidrug-resistant Acinetobacter baumannii (MDRAB) infections cause elevated rates of patient deaths in intensive care units owing to the high antibiotic resistance of the clinical isolates. The advent of multidrug-resistant A. baumannii (MDRAB) strains and the formation of their biofilms are cause for concern. Tea polyphenols (TPs), which exhibit antimicrobial activity, is an ideal alternative strategy for lowering the incidence of nosocomial bacterial infections. This study was conducted to determine the effects of TPs on MDRAB. The antimicrobial and anti-biofilm activities of TPs against MDRAB were investigated in vitro using the propidium iodide assay, scanning electron microscopy, transmission electron microscopy, crystalline violet staining and real-time quantitative PCR (qPCR). The in vivo anti-biofilm and anti-inflammatory effects of TPs were studied using a rat model of MDRAB biofilm-induced pulmonary inflammation. TPs effectively inhibited the proliferation of MDRAB and damaged its cell membrane. Additionally, they inhibited MDRAB biofilm formation by reducing the content of microbial extracellular polymeric substances and altering the expression of genes related to biofilm formation. Moreover, TPs reduced pathological features of lung injury and alleviated MDRAB biofilm-induced pneumonia in rats with a tracheal cannula, attenuating the inflammatory response by inhibiting NF-κB signaling. Our findings suggest that the anti-biofilm and anti-inflammatory activities of TPs render these naturally active compounds favorable candidates for the treatment of tracheal catheter-related infections.
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Affiliation(s)
- Sijia Xu
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, PR China; Intensive Care Unit, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, PR China
| | - Yonglin Feng
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, PR China; Intensive Care Unit, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, PR China
| | - Haonan Li
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, PR China; Intensive Care Unit, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, PR China
| | - Huijuan Huang
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, PR China; Intensive Care Unit, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, PR China
| | - Qingru Chen
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China
| | - Baokang Zhu
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China
| | - Along Liu
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China
| | - Yinghua Xu
- Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotechnology Products, National Institutes for Food and Drug Control, Beijing, 102629, PR China
| | - Xiaobao Jin
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China.
| | - Shuiqing Gui
- Intensive Care Unit, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, PR China.
| | - Xuemei Lu
- Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, PR China.
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Boziki M, Theotokis P, Kesidou E, Nella M, Bakirtzis C, Karafoulidou E, Tzitiridou-Chatzopoulou M, Doulberis M, Kazakos E, Deretzi G, Grigoriadis N, Kountouras J. Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection. Neurol Int 2024; 16:1750-1778. [PMID: 39728753 DOI: 10.3390/neurolint16060127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/08/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction. METHODS This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. RESULTS In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses. CONCLUSION As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.
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Affiliation(s)
- Marina Boziki
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Paschalis Theotokis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Evangelia Kesidou
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Nella
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Bakirtzis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleni Karafoulidou
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Tzitiridou-Chatzopoulou
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Midwifery Department, School of Healthcare Sciences, University of West Macedonia, Koila, 50100 Kozani, Greece
| | - Michael Doulberis
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, 5001 Aarau, Switzerland
| | - Evangelos Kazakos
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
| | - Georgia Deretzi
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Department of Neurology, Papageorgiou General Hospital, 54629 Thessaloniki, Greece
| | - Nikolaos Grigoriadis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
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Xie L, Liu GW, Liu YN, Li PY, Hu XN, He XY, Huan RB, Zhao TL, Guo HJ. Prevalence of Helicobacter pylori infection in China from 2014-2023: A systematic review and meta-analysis. World J Gastroenterol 2024; 30:4636-4656. [PMID: 39575409 PMCID: PMC11572641 DOI: 10.3748/wjg.v30.i43.4636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 09/19/2024] [Accepted: 10/16/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of H. pylori plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, H. pylori infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for H. pylori infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H. pylori control. AIM To methodically evaluate the occurrence of H. pylori infection throughout China and establish a reference point for subsequent investigations. METHODS A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section. RESULTS Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with H. pylori. We evaluated infection rates in mainland China and the combined prevalence of H. pylori was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7). CONCLUSION Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed.
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Affiliation(s)
- Lu Xie
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Guang-Wei Liu
- Department of Spleen, Stomach, Liver and Gallbladder, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Ya-Nan Liu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Peng-Yu Li
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Xin-Ning Hu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Xin-Yi He
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Rui-Bo Huan
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Tai-Long Zhao
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Hui-Jun Guo
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
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Krzyżek P. Helicobacter pylori Efflux Pumps: A Double-Edged Sword in Antibiotic Resistance and Biofilm Formation. Int J Mol Sci 2024; 25:12222. [PMID: 39596287 PMCID: PMC11594842 DOI: 10.3390/ijms252212222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/11/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
Helicobacter pylori is a major pathogen associated with various gastric diseases. Despite decades of research, the treatment of H. pylori remains challenging. One of the primary mechanisms contributing to failures of therapies targeting this bacterium is genetic mutations in drug target sites, although the growing body of scientific data highlights that efflux pumps may also take part in this process. Efflux pumps are proteinaceous transporters actively expelling antimicrobial agents from the interior of the targeted cells and reducing the intracellular concentration of these compounds. Considering that efflux pumps contribute to both antimicrobial resistance and biofilm formation, an in-depth understanding of their properties may constitute a cornerstone in the development of novel therapeutics against H. pylori. In line with this, the aim of the current review is to describe the multitude of efflux pumps produced by H. pylori and present the data describing the involvement of these proteins in tolerance and/or resistance to various classes of antimicrobial substances.
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Affiliation(s)
- Paweł Krzyżek
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland
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