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El-Seedi HR, Refaey MS, Abd El-Wahed AA, Albadawy A, Karav S, El-Seedi SH, Cheng G, Salem MF, Liu L, Tang J, Abolibda TZ, Zou X, Guo Z, Khalifa SAM. Bee products in the fight against Helicobacter pylori and molecular interactions. Microb Pathog 2025; 205:107707. [PMID: 40378976 DOI: 10.1016/j.micpath.2025.107707] [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: 01/25/2025] [Revised: 04/23/2025] [Accepted: 05/13/2025] [Indexed: 05/19/2025]
Abstract
Gastric or duodenal ulcers can lead to upper gastrointestinal (GI) bleeding. Infection with Helicobacter pylori (H. pylori) is one of the most common infections in the world and can cause both gastric ulcers and gastric cancer. The treatment aims to eradicate H. pylori and treatment with antibiotics has made it possible to cure gastric ulcers. The most common complication of untreated peptic ulcer disease is bleeding (hematemesis, melena, and anemia), while perforation occurs in a smaller proportion of patients. In some individuals, the infection causes mucosal changes with increasing age that lead to atrophy and intestinal metaplasia. It is believed that atrophy and especially intestinal metaplasia are a prerequisite for the most common form of gastric cancer, adenocarcinoma. There is presently a demand for an alternate treatment devoid of the current strategies drawbacks including recurrence, resistance and antibiotic abuse. The current workhighlights the possibility of bee product-based treatments for preventing and eliminating H. pylori infestation. Sci-finder, Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus were used for literature screening. Terms and keywords, i.e. "helicobacter pylori", "epidemiology", "chemotherapy", "honey", "propolis", "bee venom", "bioactive compounds", and "mechanism of action" were used in the search. Bee products are important alternatives that have been utilized for treating many ailments due to their diverse biochemical and biological characteristics. Various mechanisms, such as direct antibacterial, antioxidant, anti-inflammatory, and wound healing capacities, are proposed to explain the potential effect of bee products against H. pylori. The bee product's metabolites have a role in the adherence of H. pylori to stomach epithelial cells. The disruption of bacterial cell membranes and the inhibition of virulence factors are the two mechanisms behind the bee product's promising therapeutic applications against H. pylori.
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Affiliation(s)
- Hesham R El-Seedi
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Mohamed S Refaey
- Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia National University, Km Cairo-Alexandria Agricultural Road, Menoufia, Egypt.
| | - Aida A Abd El-Wahed
- Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, Giza 12627, Egypt.
| | - Aida Albadawy
- Translational Medicine Laboratory, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale, 17000, Turkey.
| | | | - Guiguang Cheng
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Mohamed F Salem
- Department of Environmental Biotechnology, Genetic Engineering and Biotechnology Research Institute, GEBRI, University of Sadat City, Sadat City, P.O. Box:79, Egypt.
| | - Lianliang Liu
- School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang, China.
| | - Jie Tang
- School of Food and Bioengineering, Xihua University, Chengdu, Si Chuan Province, China.
| | - Tariq Z Abolibda
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Xiaobo Zou
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Zhiming Guo
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Shaden A M Khalifa
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Neurology and Psychiatry Department, Capio Saint Göran's Hospital, Sankt Göransplan 1, 112 19, Stockholm, Sweden.
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Plewa P, Kiełbowski K, Mentel O, Figiel K, Bakinowska E, Becht R, Banach B, Pawlik A. Bacteria and Carcinogenesis and the Management of Cancer: A Narrative Review. Pathogens 2025; 14:509. [PMID: 40430828 PMCID: PMC12114594 DOI: 10.3390/pathogens14050509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2025] [Revised: 05/17/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025] Open
Abstract
There is a widely known relationship between certain microbes and cancer progression. For instance, Helicobacter pylori is associated with the occurrence of gastric cancer, while HPV is associated with cervical and head and neck cancers. Recent studies have uncovered novel and important associations between bacterial presence and tumor formation and treatment response. Apart from the influence of the intestinal microbiome on cancer, the local activity of bacteria affects disease properties as well. Bacteria can localize within tumors in less vascularized niches. Their presence mediates the activity of signaling pathways, which contribute to tumorigenesis. Furthermore, they affect the composition of the tumor microenvironment, a highly complex structure composed of immunoregulatory cells and secreted inflammatory mediators. Recently, researchers have analyzed the properties of bacteria to develop novel anticancer strategies. The aim of this review is to discuss the latest findings regarding the relationships between bacteria and cancer and the properties of bacteria that could be used to kill cancer cells.
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Affiliation(s)
- Paulina Plewa
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Kajetan Kiełbowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University, 71-252 Szczecin, Poland
| | - Oliwia Mentel
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Karolina Figiel
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Estera Bakinowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Rafał Becht
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University, 71-252 Szczecin, Poland
| | - Bolesław Banach
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.)
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Naderi Z, Mirnejad R, Bayat M. Investigation of cagA, dupA and babA genes among clinical Helicobacter pylori isolates collected from patients suffering from H. pylori gastric disease using real-time PCR. J Microbiol Methods 2025; 235:107143. [PMID: 40339813 DOI: 10.1016/j.mimet.2025.107143] [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: 03/11/2025] [Revised: 04/22/2025] [Accepted: 05/02/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection causes chronic gastritis and can lead to severe gastrointestinal diseases, including stomach ulcers, stomach cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. This infection affects about half of the world's population, with varying prevalence based on location and hygiene standards. Determining the importance of H. pylori pathogenic genes in predicting clinical outcomes is crucial, especially considering high rates of stomach cancer in Middle Eastern and Asian populations. The main aim of this study was to determine the frequency of the babA, cagA, and dupA pathogenic genes in H. pylori isolates obtained from patients with gastrointestinal diseases. METHODS A urease test was conducted on 111 biopsies from the antrum of patients undergoing endoscopies at Tehran hospitals. Following this, an extraction kit was used, and the Real-time PCR technique determined the frequency of the babA, cagA, and dupA genes. RESULTS Out of 111 stomach biopsies, 70 tested positive for H. pylori. Molecular analysis showed that the frequency of babA, cagA, and dupA genes was 51 (72.8 %), 35 (50 %), and 26 (37.14 %), respectively. CONCLUSION The results showed that babA and cagA genes were identified with a higher abundance among patients and the findings suggest that the presence of these genes could be considered a risk indicator for exacerbation of gastrointestinal disease. Additionally, the dupA gene was found with lower frequency, which is less likely to play a significant role in pathogenicity compared to other genes. This study could help develop more effective prevention and treatment methods in the future.
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Affiliation(s)
- Zahra Naderi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Reza Mirnejad
- Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Mansour Bayat
- Department of Pathobiology, Faculty of Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
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Abu-Qatouseh LF, Ahmad MIA, Amorim CG, Al-Adham ISI, Collier PJ, Montenegro MCBSM. Insights into the molecular antimicrobial properties of ferulic acid against Helicobacter pylori. J Appl Microbiol 2025; 136:lxaf112. [PMID: 40336146 DOI: 10.1093/jambio/lxaf112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 04/16/2025] [Accepted: 05/06/2025] [Indexed: 05/09/2025]
Abstract
AIM Natural compounds have gained attention as potential alternatives or adjuvants to antibiotics against several pathogens. Ferulic acid, a natural plant product, has demonstrated promising antimicrobial properties against a wide range of microorganisms. This paper aims to characterize the molecular mechanism underlying the potential inhibitory effects of ferulic acid on Helicobacter pylori. METHODS AND RESULTS The impact of ferulic acid on the growth and expression of genes associated with urease enzyme, flagellar and motility, acid stability, toxin production, and quorum sensing in H. pylori using quantitative real-time polymerase chain reaction (qPCR) was investigated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ferulic acid were 167.7 ± 58.9 µg mL-1 and 250 µg mL-1, respectively. Exposure of H. pylori to 0.1% ferulic acid revealed strong induction of the regulatory genes hup and rpoN transcription factors and fliA flagellar regulatory factor and the cytotoxin genes cagA and vacA. CONCLUSIONS Results confirm the potent anti-Helicobacter pylori activity of ferulic acid affecting the expression of genes of its virulence factors, metabolism, and quorum sensing.
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Affiliation(s)
- Luay F Abu-Qatouseh
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Mohammad I A Ahmad
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328 Amman, Jordan
- Pharmacological and Diagnostic Research Centre (PDRC), Al-Ahliyya Amman University, 19328 Amman, Jordan
| | - Célia G Amorim
- Department of Chemical Sciences, Faculty of Pharmacy, LAQV-REQUIMTE, University of Porto, Porto, 4169-007, Portugal
| | - Ibrahim S I Al-Adham
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Phillip J Collier
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Maria C B S M Montenegro
- Department of Chemical Sciences, Faculty of Pharmacy, LAQV-REQUIMTE, University of Porto, Porto, 4169-007, Portugal
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Jaiswal N, Kandpal M, Jha HC, Kumar A. Collective in-silico and in-vitro evaluation indicate natural phenolics as a potential therapeutic candidate targeting antimicrobial-resistant genes of Helicobacter pylori. Int J Biol Macromol 2025; 307:142197. [PMID: 40107545 DOI: 10.1016/j.ijbiomac.2025.142197] [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: 10/09/2024] [Revised: 02/28/2025] [Accepted: 03/15/2025] [Indexed: 03/22/2025]
Abstract
Antibiotic-resistant Helicobacter pylori is a major cause of severe gastric conditions such as ulcers and gastric cancer, with limited treatment options due to the rise of multidrug-resistant strains. This study aims to identify novel drug targets within antimicrobial resistance (AMR) genes and evaluate potential therapeutic candidates using computational and experimental approaches. AMR genes in H. pylori were identified using RAST and their essentiality, metabolic pathways, and druggability. Localization, protein family, and functional annotations were performed using QuickGO and Pfam, while Cytoscape was used for protein interaction analysis and identification of hub proteins. Ddl was selected as the target protein for further study among the AMR genes. Using the PASS tool, two phenolic compounds were identified as potential inhibitors of Ddl, and their interaction potency was confirmed through molecular docking studies. In-vitro experiments demonstrated that α-mangostin significantly attenuated H. pylori-mediated inflammatory responses in the gastric environment. Notably, α-mangostin induced the mitochondrial-mediated intrinsic apoptotic pathway in gastric epithelial cells, offering new insights into its therapeutic potential. This study identified Ddl as a promising drug target among AMR genes in H. pylori and highlighted phenolic compounds, particularly α-mangostin, as potential inhibitors. These findings contribute to the development of novel anti-H. pylori therapies address the growing challenge of antibiotic resistance and pave the way for future research into effective treatments for H. pylori infections.
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Affiliation(s)
- Neha Jaiswal
- Department of Biotechnology, National Institute of Technology, Raipur 492010, Chhattisgarh, India
| | - Meenakshi Kandpal
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, Madhya Pradesh, India
| | - Hem Chandra Jha
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, Madhya Pradesh, India.
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur 492010, Chhattisgarh, India.
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Fan X, Wang R. Drug-Related Gastric Perforation Secondary to Prolonged Febuxostat Administration: A Case Report. Clin Ther 2025:S0149-2918(25)00085-2. [PMID: 40222836 DOI: 10.1016/j.clinthera.2025.03.009] [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: 01/22/2025] [Revised: 03/11/2025] [Accepted: 03/15/2025] [Indexed: 04/15/2025]
Abstract
Febuxostat, a selective xanthine oxidase inhibitor, is regarded as the first-line therapeutic option for gout and hyperuricemia. With its extensive application, there has been a growing number of reports regarding associated adverse reactions. In this case, a 71-year-old male patient, who had been under long-term febuxostat treatment for gout, was admitted to the hospital approximately one year later due to persistent upper abdominal pain. Abdominal CT imaging revealed thickening of the gastric antrum wall, accompanied by peripheral exudation and the presence of free gas in the abdominal cavity, which was diagnosed as gastric perforation. After excluding other potential causative factors of gastric perforation, the serious adverse reaction potentially induced by febuxostat was taken into consideration.
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Affiliation(s)
- Xiaoxu Fan
- Department of Pharmacy, Nanjing Lishui People's Hospitial (Zhongda Hospital Lishui Branch), Southeast University, Nanjing, China
| | - Ran Wang
- Department of Pharmacy, Nanjing Lishui People's Hospitial (Zhongda Hospital Lishui Branch), Southeast University, Nanjing, China.
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7
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Zhu M, Xu X, Cai P, Wang T, Zhu M, Yan C, Pan Q, Chen C, Wu Y, Zhang G, Jin G. Global Population Structure, Virulence Factors and Antibiotic Resistance of Helicobacter pylori: A Pooled Analysis of 4067 Isolates From 76 Countries. Helicobacter 2025; 30:e70025. [PMID: 40059062 DOI: 10.1111/hel.70025] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/20/2024] [Accepted: 02/27/2025] [Indexed: 05/13/2025]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a common pathogen that has co-evolved with the human host for approximately 100,000 years; however, our understanding of its population structure remains limited. Furthermore, the detailed characteristics of its virulence factors and antibiotic resistance for H. pylori are not yet fully elucidated. METHODS In this study, we curated a global genome dataset of 4067 H. pylori isolates from 76 countries and explored H. pylori characteristics, including population genetic structure, virulence factors, and antibiotic resistance. We used three approaches (fineSTRUCTURE, ADMIXTURE, and DAPC) to infer the population structure of H. pylori. We investigated the virulence of each isolate by calling genotypes of cagA and vacA and evaluated the correlations of virulence factors with subpopulation. For antibiotic resistance, we identified mutations to determine the genotypic antibiotic resistance. Then we estimated the prevalence of genotypic antibiotic resistance grouped by geographical location, subpopulation, and study period. RESULT We identified 21 subpopulations in 4067 H. pylori isolates, including 20 previously reported subpopulations and a novel subpopulation hspEuropeIsrael, and found that the population structure of H. pylori was geographically restricted. The novel subpopulation hspEuropeIsrael had a higher proportion of less virulent cagA and vacA genotypes compared to other subpopulations. After evaluating the rates of H. pylori genotypic resistance to four antibiotics, we found that the prevalence of genotypic resistance to amoxicillin and metronidazole was > 15% across all five continents. Genotypic resistance to levofloxacin was > 15% on all continents except for Oceania. Additionally, the genotypic resistance rate to clarithromycin was > 15% in Asia, Europe, and Oceania. A trend of increased genotypic resistance over time was observed in several continents during subgroup analyses. Furthermore, we constructed a comprehensive database for H. pylori, named Helicobacter Pylori Encyclopedia for Research (HELPER, http://ccra.njmu.edu.cn/helper). CONCLUSION Our results provide a detailed characterization of H. pylori and extend previous schemas. HELPER serves as an informative and comprehensive database that will be a valuable resource for researchers and lay the foundation for future studies on H. pylori.
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Affiliation(s)
- Mengyi Zhu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Xianfeng Xu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Pengpeng Cai
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Tianpei Wang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Public Health Institute of Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Meng Zhu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Caiwang Yan
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Immunology, Key Laboratory of Immunological Environment and Disease, Nanjing Medical University, Nanjing, China
| | - Qianglong Pan
- Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Chen Chen
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Ying Wu
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Guoxin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Guangfu Jin
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
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Wang N, Wu S, Huang L, Hu Y, He X, He J, Hu B, Xu Y, Rong Y, Yuan C, Zeng X, Wang F. Intratumoral microbiome: implications for immune modulation and innovative therapeutic strategies in cancer. J Biomed Sci 2025; 32:23. [PMID: 39966840 PMCID: PMC11837407 DOI: 10.1186/s12929-025-01117-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 01/09/2025] [Indexed: 02/20/2025] Open
Abstract
Recent advancements have revealed the presence of a microbiome within tumor tissues, underscoring the crucial role of the tumor microbiome in the tumor ecosystem. This review delves into the characteristics of the intratumoral microbiome, underscoring its dual role in modulating immune responses and its potential to both suppress and promote tumor growth. We examine state-of-the-art techniques for detecting and analyzing intratumoral bacteria, with a particular focus on their interactions with the immune system and the resulting implications for cancer prognosis and treatment. By elucidating the intricate crosstalk between the intratumoral microbiome and the host immune system, we aim to uncover novel therapeutic strategies that enhance the efficacy of cancer treatments. Additionally, this review addresses the existing challenges and future prospects within this burgeoning field, advocating for the integration of microbiome research into comprehensive cancer therapy frameworks.
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Affiliation(s)
- Na Wang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Si Wu
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Lanxiang Huang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yue Hu
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Xin He
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Jourong He
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Ben Hu
- Center for Tumor Precision Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yaqi Xu
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yuan Rong
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Chunhui Yuan
- Department of Laboratory Medicine, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, China.
| | - Xiantao Zeng
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
| | - Fubing Wang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, 430071, China.
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Muñoz AB, Stepanian J, Solano‐Gutierrez JS, Vale FF, Trespalacios‐Rangel AA. Helicobacter pylori Infection in Colombia: Phylogeny, Resistome, and Virulome. APMIS 2025; 133:e70003. [PMID: 39930978 PMCID: PMC11811748 DOI: 10.1111/apm.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 11/06/2024] [Accepted: 01/27/2025] [Indexed: 02/13/2025]
Abstract
Helicobacter pylori is a successful etiologic gastric agent that reaches a prevalence around 80% in Colombia. This bacterium is extremely diverse and has shown a phylogeographic pattern. The objective of this study was to perform an analysis of genomic epidemiology of H. pylori in Colombia. We enriched our set of 29 newly sequenced Colombian H. pylori genomes with additional data from public databases, reaching a total of 221 genomes in our dataset. Phylogenetic characterization was carried out using MLST and whole genome SNP analysis. We also performed a characterized the diversity of virulence factors and mutations associated with antimicrobial resistance. Phylogenetic analyzes showed two new Colombian H. pylori clades. Furthermore, many virulence genotype combinations were found, mutations associated with resistance were found for all the studied antibiotics, highlighting 14.4% of the genomes presented profiles associated with resistance to more than one family of antibiotics. Our analyzes described the genomics of Colombian H. pylori and verify the presence of a population group formed exclusively by Colombian isolates. We demonstrated the great diversity among the isolates and that the analysis by comparative genomics of H. pylori are valuable tools to assess the diversity, virulence, and resistance of H. pylori.
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Affiliation(s)
- Angela B. Muñoz
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
- Health Sciences FacultyUniversidad Colegio Mayor de CundinamarcaBogotáColombia
| | - Johanna Stepanian
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
| | - Juan S. Solano‐Gutierrez
- Texas Tech University—School of Veterinary MedicineAmarilloTexasUSA
- Texas Center for Comparative Cancer Research (TC3R)AmarilloTexasUSA
| | - Filipa F. Vale
- BioISI—Instituto de Biosistemas e Ciências Integrativas, Faculdade de CiênciasUniversidade de LisboaLisboaPortugal
- Research Institute for Medicines (iMed.ULisboa), Faculty of PharmacyUniversidade de LisboaLisboaPortugal
| | - Alba A. Trespalacios‐Rangel
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
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Elbehiry A, Marzouk E, Abalkhail A, Sindi W, Alzahrani Y, Alhifani S, Alshehri T, Anajirih NA, ALMutairi T, Alsaedi A, Alzaben F, Alqrni A, Draz A, Almuzaini AM, Aljarallah SN, Almujaidel A, Abu-Okail A. Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development. Front Med (Lausanne) 2025; 11:1523991. [PMID: 39850097 PMCID: PMC11756510 DOI: 10.3389/fmed.2024.1523991] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025] Open
Abstract
One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.
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Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Eman Marzouk
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Wael Sindi
- Department of Population, Public and Environmental Health, General Administration of Health Services, Ministry of Defense, Riyadh, Saudi Arabia
| | - Yasir Alzahrani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Salem Alhifani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Turki Alshehri
- Department of Dental, Alhada Armed Forces Hospital, Taif, Saudi Arabia
| | - Nuha Abdulaziz Anajirih
- Department of Medical Emergency Services, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah, Saudi Arabia
| | - Turki ALMutairi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ahmad Alsaedi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Abdullah Alqrni
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah, Saudi Arabia
| | - Abdelmaged Draz
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Abdulaziz M. Almuzaini
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Sahar N. Aljarallah
- Department of Pharmacy Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia
| | - Abdulrahman Almujaidel
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Akram Abu-Okail
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
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11
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Cao L, Wang X, Ma X, Zhu G, Li J. Exploration of Constitutional Bias and Associated Factors in Patients with Recurrent and Metastatic Gastric Cancer, and the Therapeutic Effect of Yiqi Wenyang Jiedu Prescription: A one-arm study. Integr Cancer Ther 2025; 24:15347354251331100. [PMID: 40248901 PMCID: PMC12034998 DOI: 10.1177/15347354251331100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 03/15/2025] [Indexed: 04/19/2025] Open
Abstract
OBJECTIVE This study was conducted to elucidate the distribution characteristics of predominant unbalanced constitutions and TCM syndrome elements in patients with recurrent and metastatic gastric cancer. This study was also undertaken to analyze the potential relationship between the body constitutions of patients, syndrome elements, and biological indicators, as well as to investigate the effect of Yiqi Wenyang Jiedu prescription (YWJP) on symptoms and biological indicators before and after treatment. RESULT Yang-deficiency and Qi-deficiency were identified as prevalent imbalanced constitutions among patients with recurrent and metastatic gastric cancer. The primary syndrome factors associated with disease localization included the spleen-stomach and liver, with the main syndrome elements being Qi-deficiency, Yang-deficiency, and Qi-stagnation. Patients with Qi-deficiency and Yang-deficiency constitutions exhibited lower BMI and higher monocyte-to-lymphocyte ratio (MLR). A notable positive correlation was observed between cold (Yang-deficiency) and BMI, as well as between Qi-deficiency constitution and neutrophil-to-lymphocyte ratio (NLR). Furthermore, YWJP demonstrated efficacy in alleviating symptoms associated with Qi-deficiency and Yang-deficiency in patients with recurrent and metastatic gastric cancer, including dyspnea, fatigue, diaphoresis, cold intolerance, abdominal sounds, postural changes, and abdominal distension. DISCUSSION Yang-deficiency and Qi-deficiency emerged as prevalent constitutional patterns in patients with recurrent and metastatic gastric cancer. Notably, BMI, MLR, and NLR may serve as physiological indicators of these conditions. Furthermore, YWJP treatment demonstrated potential efficacy in alleviating symptoms associated with Qi-deficiency and Yang-deficiency in this patient population. CLINICAL TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2200055826.
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Affiliation(s)
- Luchang Cao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinmiao Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinyi Ma
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guanghui Zhu
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Li
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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12
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Verma J, Anwar MT, Linz B, Backert S, Pachathundikandi SK. The Influence of Gastric Microbiota and Probiotics in Helicobacter pylori Infection and Associated Diseases. Biomedicines 2024; 13:61. [PMID: 39857645 PMCID: PMC11761556 DOI: 10.3390/biomedicines13010061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota's composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general.
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Affiliation(s)
- Jagriti Verma
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
| | - Md Tanveer Anwar
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
| | - Bodo Linz
- Chair of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Steffen Backert
- Chair of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Suneesh Kumar Pachathundikandi
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
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13
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Bawali P, Brahma A, Rana SR, Pal A, Bhattacharyya A. Helicobacter pylori infection and inflammatory events: the extracellular vesicle-connect in driving gastrointestinal tract cancers. Front Med (Lausanne) 2024; 11:1444242. [PMID: 39610678 PMCID: PMC11602329 DOI: 10.3389/fmed.2024.1444242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 10/28/2024] [Indexed: 11/30/2024] Open
Affiliation(s)
| | | | | | | | - Asima Bhattacharyya
- School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, An OCC of Homi Bhabha National Institute, Khurda, Odisha, India
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14
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Tandon A, Baral B, Saini V, Kandpal M, Dixit AK, Parmar HS, Meena AK, Chandra Jha H. The role of Helicobacter pylori in augmenting the severity of SARS-CoV-2 related gastrointestinal symptoms: An insight from molecular mechanism of co-infection. Heliyon 2024; 10:e37585. [PMID: 39364240 PMCID: PMC11447314 DOI: 10.1016/j.heliyon.2024.e37585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 08/24/2024] [Accepted: 09/05/2024] [Indexed: 10/05/2024] Open
Abstract
Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.
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Affiliation(s)
- Akrati Tandon
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Budhadev Baral
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Vaishali Saini
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Meenakshi Kandpal
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Amit Kumar Dixit
- Central Ayurveda Research Institute, Kolkata, 4-CN Block, Sector –V, Bidhannagar, Kolkata, 700 091, India
| | - Hamendra Singh Parmar
- School of Biotechnology, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Indore, Madhya Pradesh, 452001, India
| | - Ajay Kumar Meena
- Regional Ayurveda Research Institute, Amkhoh, Gwalior, Madhya Pradesh, 474001, India
| | - Hem Chandra Jha
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
- Centre for Rural Development and Technology, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
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15
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Mazurek M, Szewc M, Sitarz MZ, Dudzińska E, Sitarz R. Gastric Cancer: An Up-to-Date Review with New Insights into Early-Onset Gastric Cancer. Cancers (Basel) 2024; 16:3163. [PMID: 39335135 PMCID: PMC11430327 DOI: 10.3390/cancers16183163] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/06/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the fifth most common cause of cancer death in the world. Regarding the age at which the diagnosis was made, GC is divided into early-onset gastric cancer (EOGC-up to 45 years of age) and conventional GC (older than 45). EOGC constitutes approximately 10% of all GCs. Numerous reports indicate that EOGC is more aggressive than conventional GC and is often discovered at an advanced tumor stage, which has an impact on the five-year survival rate. The median survival rate for advanced-stage GC is very poor, amounting to less than 12 months. Risk factors for GC include family history, alcohol consumption, smoking, Helicobacter pylori, and Epstein-Barr virus infection. It has been shown that a proper diet and lifestyle can play a preventive role in GC. However, research indicates that risk factors for conventional GC are less correlated with EOGC. In addition, the unclear etiology of EOGC and the late diagnosis of this disease limit the possibilities of effective treatment. Genetic factors are considered a likely cause of EOGC, as young patients are less exposed to environmental carcinogens. Research characterizing GC in young patients is scarce. This comprehensive study presents all aspects: epidemiology, risk factors, new treatment strategies, and future directions.
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Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Masovian Cancer Hospital, 05-135 Wieliszew, Poland;
| | - Monika Szewc
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Monika Z. Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Ewa Dudzińska
- Department of Dietetics and Nutrition Education, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Robert Sitarz
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland;
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
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16
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Leone A, De la Fuente-Arrillaga C, Mas MV, Sayon-Orea C, Menichetti F, Martínez-Gonzalez MA, Bes-Rastrollo M. Association between the consumption of ultra-processed foods and the incidence of peptic ulcer disease in the SUN project: a Spanish prospective cohort study. Eur J Nutr 2024; 63:2367-2378. [PMID: 38809325 PMCID: PMC11377682 DOI: 10.1007/s00394-024-03439-2] [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: 02/01/2024] [Accepted: 05/14/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE Consumption of ultra-processed foods (UPF) has increased despite potential adverse health effects. Recent studies showed an association between UPF consumption and some gastrointestinal disorders. We evaluated the association between UPF consumption and peptic ulcer disease (PUD) in a large Spanish cohort. METHODS We conducted a prospective analysis of 18,066 participants in the SUN cohort, followed every two years. UPF was assessed at baseline and 10 years after. Cases of PUD were identified among participants reporting a physician-made diagnosis of PUD during follow-ups. Cases were only partially validated against medical records. Cox regression was used to assess the association between baseline UPF consumption and PUD risk. Based on previous findings and biological plausibility, socio-demographic and lifestyle variables, BMI, energy intake, Helicobacter pylori infection, gastrointestinal disorders, aspirin and analgesic use, and alcohol and coffee consumption were included as confounders.We fitted GEE with repeated dietary measurements at baseline and after 10 years of follow-up. Vanderweele's proposed E value was calculated to assess the sensitivity of observed associations to uncontrolled confounding. RESULTS During a median follow-up of 12.2 years, we recorded 322 new PUD cases (1.56 cases/1000 person-years). Participants in the highest baseline tertile of UPF consumption had an increased PUD risk compared to participants in the lowest tertile (HR = 1.52, 95% CI: 1.15, 2.00, Ptrend=0.002). The E-values for the point estimate supported the observed association. The OR using repeated measurements of UPF intake was 1.39 (95% CI: 1.03, 1.87) when comparing extreme tertiles. CONCLUSION The consumption of UPF is associated with an increased PUD risk.
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Affiliation(s)
- Alessandro Leone
- International Center for the Assessment of Nutritional Status and The Development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.
- Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, 20100, Italy.
| | - Carmen De la Fuente-Arrillaga
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
- CIBERobn, Instituto de Salud Carlos III, Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | | | - Carmen Sayon-Orea
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
- CIBERobn, Instituto de Salud Carlos III, Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Navarra Institute of Public Health, Pamplona, Spain
| | - Francesca Menichetti
- International Center for the Assessment of Nutritional Status and The Development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Miguel Angel Martínez-Gonzalez
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
- CIBERobn, Instituto de Salud Carlos III, Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Maira Bes-Rastrollo
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
- CIBERobn, Instituto de Salud Carlos III, Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
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17
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Paes Dutra JA, Gonçalves Carvalho S, Soares de Oliveira A, Borges Monteiro JR, Rodrigues Pereira de Oliveira Borlot J, Tavares Luiz M, Bauab TM, Rezende Kitagawa R, Chorilli M. Microparticles and nanoparticles-based approaches to improve oral treatment of Helicobacter pylori infection. Crit Rev Microbiol 2024; 50:728-749. [PMID: 37897442 DOI: 10.1080/1040841x.2023.2274835] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 10/17/2023] [Indexed: 10/30/2023]
Abstract
Helicobacter pylori is a gram-negative, spiral-shaped, flagellated bacterium that colonizes the stomach of half the world's population. Helicobacter pylori infection causes pathologies of varying severity. Standard oral therapy fails in 15-20% since the barriers of the oral route decrease the bioavailability of antibiotics and the intrinsic factors of bacteria increase the rates of resistance. Nanoparticles and microparticles are promising strategies for drug delivery into the gastric mucosa and targeting H. pylori. The variety of building blocks creates systems with distinct colloidal, surface, and biological properties. These features improve drug-pathogen interactions, eliminate drug depletion and overuse, and enable the association of multiple actives combating H. pylori on several fronts. Nanoparticles and microparticles are successfully used to overcome the barriers of the oral route, physicochemical inconveniences, and lack of selectivity of current therapy. They have proven efficient in employing promising anti-H. pylori compounds whose limitation is oral route instability, such as some antibiotics and natural products. However, the current challenge is the applicability of these strategies in clinical practice. For this reason, strategies employing a rational design are necessary, including in the development of nano- and microsystems for the oral route.
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Affiliation(s)
| | | | | | | | | | - Marcela Tavares Luiz
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
| | - Tais Maria Bauab
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
| | | | - Marlus Chorilli
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
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18
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He W, Zhang Y. Analysis of factors associated with Helicobacter pylori infection in severe pancreatitis patients and its effect on patient's prognosis. Am J Transl Res 2024; 16:4011-4019. [PMID: 39262733 PMCID: PMC11384374 DOI: 10.62347/jkef1700] [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: 03/28/2024] [Accepted: 07/06/2024] [Indexed: 09/13/2024]
Abstract
OBJECTIVE To analyze the factors related to Helicobacter pylori (Hp) infection in patients with severe acute pancreatitis (SAP) and to observe the effect of Hp on SAP, and to provide a reference for future clinical prevention and treatment of Hp infection in SAP. METHODS A retrospective analysis was performed on 77 SAP patients admitted to Pingxiang People's Hospital between January 2020 and February 2022, with 33 Hp-infected individuals as the Hp-positive group and the other 44 patients being without Hp infection served as the Hp-negative group. First, the related factors of Hp infection in SAP patients were analyzed with multiple Logistic regression. Subsequently, the Acute Physiology and Chronic Health Evaluation II (APACHE II), Bedside Index for Severity in Acute Pancreatitis (BISAP) and Modified CT Severity Index (MCTSI) scores, as well as the levels of C-reactive protein (CRP), white blood cell (WBC), procalcitonin (PCT) and immunoglobulins A/M/G (IgA, IgM, and IgG) were recorded for inter-group comparisons. The adverse reactions and hospitalization time were also recorded. Besides, a six-month follow-up was carried out after discharge, and patients' quality of life was evaluated using the Short-Form 36 Item Health Survey (SF-36). RESULTS Logistic regression analysis identified that history of Hp infection, long-term drinking, eating habits and history of biliary tract diseases were independent risk factors for Hp infection (all P<0.05). At 2 weeks after admission, higher APACHE II, BISAP and MCTSI scores were observed in Hp-positive group compared with Hp-negative group (all P<0.05). The Hp-positive group exhibited higher CRP, WBC and PCT levels while lower IgA, IgM and IgG levels during treatment compared to the Hp-negative group (all P<0.05). No difference was found in the incidence of adverse reactions between the two groups (P>0.05), but the hospitalization time of the Hp-positive group was significantly prolonged (P<0.05). The follow-up results determined better quality of life in the Hp-negative group, which resulted in higher SF-36 scores in various dimensions (P<0.05). CONCLUSION The history of Hp infection, long-term drinking, eating habits, and history of biliary tract diseases are all independent risk factors for Hp infection. Hp infection exacerbates disease progression of SAP, adversely influences patients' recovery, impairs their immune function, and compromises their prognoses.
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Affiliation(s)
- Wencheng He
- Department of Critical Medicine, Pingxiang People's Hospital Pingxiang 337055, Jiangxi, China
| | - Yonggen Zhang
- Department of Critical Medicine, Pingxiang People's Hospital Pingxiang 337055, Jiangxi, China
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19
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Shirani M, Shariati S, Bazdar M, Sojoudi Ghamnak F, Moradi M, Shams Khozani R, Taki E, Arabsorkhi Z, Heidary M, Eskandari DB. The immunopathogenesis of Helicobacter pylori-induced gastric cancer: a narrative review. Front Microbiol 2024; 15:1395403. [PMID: 39035439 PMCID: PMC11258019 DOI: 10.3389/fmicb.2024.1395403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 05/06/2024] [Indexed: 07/23/2024] Open
Abstract
Helicobacter pylori infection is a well-established risk factor for the development of gastric cancer (GC). Understanding the immunopathogenesis underlying this association is crucial for developing effective preventive and therapeutic strategies. This narrative review comprehensively explores the immunopathogenesis of H. pylori-induced GC by delving into several key aspects, emphasizing the pivotal roles played by H. pylori virulence factors, including cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA), blood group antigen-binding adhesin (babA), and sialic acid binding adhesin (sabA). Moreover, the review focuses on the role of toll-like receptors (TLRs) and cytokines in the complex interplay between chronic infection and gastric carcinogenesis. Finally, the study examines the association between H. pylori evasion of the innate and adaptive immune response and development of GC. A comprehensive understanding of the immunopathogenesis of H. pylori-induced GC is essential for designing targeted interventions to prevent and manage this disease. Further research is warranted to elucidate the intricate immune responses involved and identify potential therapeutic targets to improve patient outcomes.
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Affiliation(s)
- Maryam Shirani
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Saeedeh Shariati
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Monireh Bazdar
- School of Medicine, Razi Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Melika Moradi
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Elahe Taki
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Arabsorkhi
- Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
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Boyanova L, Medeiros J, Yordanov D, Gergova R, Markovska R. Turmeric and curcumin as adjuncts in controlling Helicobacter pylori-associated diseases: a narrative review. Lett Appl Microbiol 2024; 77:ovae049. [PMID: 38794899 DOI: 10.1093/lambio/ovae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/19/2024] [Accepted: 05/23/2024] [Indexed: 05/26/2024]
Abstract
Non-antibiotic adjuncts may improve Helicobacter pylori infection control. Our aim was to emphasize curcumin benefits in controlling H. pylori infection. We discussed publications in English mostly published since 2020 using keyword search. Curcumin is the main bioactive substance in turmeric. Curcumin inhibited H. pylori growth, urease activity, three cag genes, and biofilms through dose- and strain-dependent activities. Curcumin also displayed numerous anticancer activities such as apoptosis induction, anti-inflammatory and anti-angiogenic effects, caspase-3 upregulation, Bax protein enhancement, p53 gene activation, and chemosensitization. Supplementing triple regimens, the agent increased H. pylori eradication success in three Iranian studies. Bioavailability was improved by liposomal preparations, lipid conjugates, electrospray-encapsulation, and nano-complexation with proteins. The agent was safe at doses of 0.5->4 g daily, the most common (in 16% of the users) adverse effect being gastrointestinal upset. Notably, curcumin favorably influences the intestinal microbiota and inhibits Clostridioides difficile. Previous reports showed the inhibitory effect of curcumin on H pylori growth. Curcumin may become an additive in the therapy of H. pylori infection, an adjunct for gastric cancer control, and an agent beneficial to the intestinal microbiota. Further examination is necessary to determine its optimal dosage, synergy with antibiotics, supplementation to various eradication regimens, and prophylactic potential.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - José Medeiros
- Gastroenterology Clinic, Rua do Carmo, 75-1º AA,, 3000 Coimbra, Portugal
| | - Daniel Yordanov
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Raina Gergova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Rumyana Markovska
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
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Sedarat Z, Taylor-Robinson AW. Helicobacter pylori Outer Membrane Proteins and Virulence Factors: Potential Targets for Novel Therapies and Vaccines. Pathogens 2024; 13:392. [PMID: 38787244 PMCID: PMC11124246 DOI: 10.3390/pathogens13050392] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/12/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024] Open
Abstract
Helicobacter pylori is a gastric oncopathogen that infects over half of the world's human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost the pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.
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Affiliation(s)
- Zahra Sedarat
- Cellular & Molecular Research Centre, Shahrekord University of Medical Sciences, Shahrekord 8813833435, Iran;
| | - Andrew W. Taylor-Robinson
- College of Health Sciences, VinUniversity, Gia Lam District, Hanoi 67000, Vietnam
- Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 1904, USA
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Said ZNA, El-Nasser AM. Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients. World J Gastroenterol 2024; 30:2302-2307. [PMID: 38813047 PMCID: PMC11130578 DOI: 10.3748/wjg.v30.i17.2302] [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: 02/18/2024] [Revised: 03/09/2024] [Accepted: 04/15/2024] [Indexed: 04/30/2024] Open
Abstract
In this editorial, we discuss the article in the World Journal of Gastroenterology. The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Medical Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Nasr City 11754, Cairo, Egypt
| | - Asmaa Mohamed El-Nasser
- Department of Medical Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Nasr City 11754, Cairo, Egypt
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Liu Y, Yang DQ, Jiang JN, Jiao Y. Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer. World J Gastrointest Surg 2024; 16:1008-1016. [PMID: 38690050 PMCID: PMC11056658 DOI: 10.4240/wjgs.v16.i4.1008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/01/2024] [Accepted: 03/13/2024] [Indexed: 04/22/2024] Open
Abstract
Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.
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Affiliation(s)
- Ying Liu
- Department of General Surgery, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
| | - Ding-Quan Yang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Jun-Nan Jiang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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Fekadu S, Kibru S, Tesfaye S, Egeno T, Tamiso A, Engiso H, Deyno S. Prevalence of Helicobacter pylori infection and effectiveness of first-line triple eradication therapy among dyspeptic patients at hospitals in Hawassa City, Ethiopia: a cross-sectional follow-up study. Gut Pathog 2024; 16:23. [PMID: 38678267 PMCID: PMC11056052 DOI: 10.1186/s13099-024-00618-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 04/19/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Dyspepsia is a common gastrointestinal illness sometimes associated with Helicobacter pylori (H. pylori) infection. Screening and eradicating the bacterium reduces the risk of infection-related complications. The aim of this study was to determine the magnitude of H. pylori infection among dyspeptic patients and the effectiveness of triple eradication therapy at hospitals in Hawassa city, Ethiopia. RESULTS The prevalence of H. pylori infection was 48.5%. The H. pylori eradication rate using first-line triple therapy was 83.8%. Eradication therapy failure is associated with previous exposure compared to no exposure (AOR: 4.8, 95% CI: 1.37-10.97), a regimen for 10-days compared to 14-days (AOR: 4.05, 95% CI: 1.42-11.55), and self-reported side effects compared to no report (AOR: 2.5, 95% CI: 1.12-5.97). Based on Morisky-eight scale 230 (79.0%) patients were adherent to their triple therapy. Participants with no reports of adverse effects showed increased odds of adherence to triple therapy compared to those who had reports (AOR = 2.45, 95% CI: 1.29-4.62). CONCLUSIONS This study demonstrated that about half of adult dyspeptic patients were infected with H. pylori, and moderate eradication was observed. Factors such as previous history of eradication therapy, duration of the eradication regimen, and perception of potential adverse effects are associated with eradication rate and should be considered during the initiation of eradication therapy.
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Affiliation(s)
- Sintayehu Fekadu
- School of Laboratory Sciences, College of Medicine and Health Sciences, Hawassa University, P. O. Box 1560, Hawassa, Ethiopia.
| | - Seyife Kibru
- Department of Internal Medicine, College of Medicine and Health Sciences, Hawassa University, P. O. Box 1560, Hawassa, Ethiopia
| | - Sisay Tesfaye
- Department of Internal Medicine, College of Medicine and Health Sciences, Hawassa University, P. O. Box 1560, Hawassa, Ethiopia
| | - Tariku Egeno
- Internal Medicine and Cardiology Unit, Abem Primary Hospital, P. O. Box 1162, Hawassa, Ethiopia
| | - Alemu Tamiso
- School of Public Health, College of Medicine and Health Sciences, Hawassa University, P.O. Box 1560, Hawassa, Ethiopia
| | - Hizkel Engiso
- School of Pharmacy, College of Medicine and Health Sciences, Hawassa University, P. O. Box 1560, Hawassa, Ethiopia
| | - Serawit Deyno
- School of Pharmacy, College of Medicine and Health Sciences, Hawassa University, P. O. Box 1560, Hawassa, Ethiopia
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Zhang Q, Mu Y, Jiang X, Zhao Y, Wang Q, Shen Z. Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1335149. [PMID: 38737547 PMCID: PMC11082308 DOI: 10.3389/fendo.2024.1335149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 04/15/2024] [Indexed: 05/14/2024] Open
Abstract
Backgroud Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. Materials and methods This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. Results According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. Conclusions In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.
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Affiliation(s)
- Qi Zhang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Yongliang Mu
- Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xin Jiang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Yirui Zhao
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Qiutao Wang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Zhen Shen
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Wongsuwanlert M, Teanpaisan R, Pahumunto N, Kaewdech A, Ruangsri P, Sunpaweravong S. Prevalence and virulence factors of Helicobacter pylori isolated from oral cavity of non-disease, gastritis, and gastric cancer patients. J Dent Sci 2024; 19:1036-1043. [PMID: 38618069 PMCID: PMC11010610 DOI: 10.1016/j.jds.2023.06.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 06/23/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND/PURPOSE The oral cavity is considered a reservoir of Helicobacter pylori associated with gastric infection. It aimed to examine the prevalence of H. pylori strains from the oral cavity and gastric tissue of patients with different stage of gastric-diseases. Strains were further characterized for virulence genes, adhesion ability, and inflammation responses. MATERIALS AND METHODS 11 non-disease, 15 gastritis, and 15 gastric cancer participated in the study. After clinical examination, gastric biopsies, saliva and plaque samples were collected and H. pylori levels were examined by real-time PCR and cultivation. The cagA and vacA genes were investigated from the culture strains. Adhesion ability and pro-inflammatory responses were analyzed in comparison between the presence of virulent genes and disease status. RESULTS Relatively poor periodontal condition was found among gastric cancer patients. Prevalence of H. pylori-positive was 84.8% and 19.5% by real-time PCR and cultivation, respectively. The cagA and vacA gene-positive strains were 52.6% and 5.3%, respectively, which were found more in gastric cancer patients. The cagA gene-positive strains were found to be higher in gastric cancer patients, and strains had significantly higher adhesion ability and pro-inflammation expressions than the cagA gene-negative strains. CONCLUSION Colonization by H. pylori in oral cavity was confirmed, and the cagA gene-positive strains play a crucial role in both adhesion and inflammatory responses. The presence of H. pylori and its virulence gene in oral cavity should be received attention. An eradication of such strains from oral cavity may help to prevent the transmission and recolonization to gastric organs.
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Affiliation(s)
- Mutita Wongsuwanlert
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Rawee Teanpaisan
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Nuntiya Pahumunto
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Oral Diagnostic Sciences, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Praphansri Ruangsri
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Somkiat Sunpaweravong
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
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Elghannam MT, Hassanien MH, Ameen YA, Turky EA, ELattar GM, ELRay AA, ELTalkawy MD. Helicobacter pylori and oral-gut microbiome: clinical implications. Infection 2024; 52:289-300. [PMID: 37917397 PMCID: PMC10954935 DOI: 10.1007/s15010-023-02115-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 10/09/2023] [Indexed: 11/04/2023]
Abstract
More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is probably a commensal organism that has been associated with the development of gastritis, ulcers, and gastric cancer. H. pylori alone is most probably not enough for the development of gastric carcinoma, but evidence for its association with the disease is high and has, therefore, been classified by the International Agency for Research on Cancer as a Class 1 carcinogen. Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the oral-gut axis. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Therefore, therapy regimens integrated with probiotics may abolish the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. The eradication therapy not only affects gut microbiome but also affects the oral microbiome with robust predominance of harmful bacteria. However, there have been reports of a protective role of H. pylori in Barrett's esophagus, esophageal adenocarcinoma, eosinophilic esophagitis, IBD, asthma, and even multiple sclerosis. Therefore, eradication therapy should be carefully considered, and test to treat policy should be tailored to specific communities especially in highly endemic areas. Supplementation of probiotics, prebiotics, herbals, and microbial metabolites to reduce the negative effects of eradication therapy should be considered. After failure of many eradication attempts, the benefits of H. pylori eradication should be carefully balanced against the risk of adverse effects especially in the elderly, persons with frailty, and intolerance to antibiotics.
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Affiliation(s)
- Maged T Elghannam
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt.
| | - Moataz H Hassanien
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Yosry A Ameen
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Emad A Turky
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Gamal M ELattar
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Ahmed A ELRay
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mohammed D ELTalkawy
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
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Akhlaghi H, Javan AJ, Chashmi SHE. Helicobacter pullorum and Helicobacter canadensis: Etiology, pathogenicity, epidemiology, identification, and antibiotic resistance implicating food and public health. Int J Food Microbiol 2024; 413:110573. [PMID: 38246022 DOI: 10.1016/j.ijfoodmicro.2024.110573] [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: 10/19/2023] [Revised: 12/29/2023] [Accepted: 01/07/2024] [Indexed: 01/23/2024]
Abstract
Nowadays, it is well-established that the consumption of poultry meat, especially chicken meat products has been drastically increasing. Even though more attentions are being paid to the major foodborne pathogens, it seems that scientists in the area of food safety and public health would prefer tackling the minor food borne zoonotic emerging or reemerging pathogens, namely Helicobacter species. Recently, understanding the novel aspects of zoonotic Enterohepatic Helicobacter species, including pathogenesis, isolation, identification, and genomic features is regarded as a serious challenge. In this regard, considerable attention is given to emerging elusive zoonotic Enterohepatic Helicobacter species, comprising Helicobacter pullorum and Helicobacter canadensis. In conclusion, the current review paper would attempt to elaborately summarize and somewhat compare the etiology, pathogenesis, cultivation process, identification, genotyping, and antimicrobial resistance profile of both H. pullorum and H. Canadensis. Further, H. pullorum has been introduced as the most significant food borne pathogen in chicken meat products.
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Affiliation(s)
- Hosein Akhlaghi
- Faculty of Veterinary Medicine, Semnan University, Semnan, Iran
| | - Ashkan Jebelli Javan
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran.
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Lei C, Xu Y, Zhang S, Huang C, Qin J. The role of microbiota in gastric cancer: A comprehensive review. Helicobacter 2024; 29:e13071. [PMID: 38643366 DOI: 10.1111/hel.13071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/19/2024] [Accepted: 03/25/2024] [Indexed: 04/22/2024]
Abstract
BACKGROUND Gastric cancer (GC) continues to pose a significant global threat in terms of cancer-related fatalities. Despite notable advancements in medical research and therapies, further investigation is warranted to elucidate its underlying etiology and risk factors. Recent times have witnessed an escalated emphasis on comprehending the role of the microbiota in cancer development. METHODS This review briefly delves into recent developments in microbiome-related research pertaining to gastric cancer. RESULTS According to studies, the microbiota can influence GC growth by inciting inflammation, disrupting immunological processes, and generating harmful microbial metabolites. Furthermore, there is ongoing research into how the microbiome can impact a patient's response to chemotherapy and immunotherapy. CONCLUSION The utilization of the microbiome for detecting, preventing, and managing stomach cancer remains an active area of exploration.
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Affiliation(s)
- Changzhen Lei
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yitian Xu
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shaopeng Zhang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing Qin
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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30
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Guan X, Ning J, Fu W, Wang Y, Zhang J, Ding S. Helicobacter pylori with trx1 high expression promotes gastric diseases via upregulating the IL23A/NF-κB/IL8 pathway. Helicobacter 2024; 29:e13072. [PMID: 38686467 DOI: 10.1111/hel.13072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 03/19/2024] [Accepted: 03/28/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Helicobacter pylori infection is one of the main causes of gastric cancer. thioredoxin-1 (Trx1) and arginase (RocF) expressed by H. pylori were found to be closely related to its pathogenicity. However, whether Trx1 and RocF can be used in clinical screening of highly pathogenic H. pylori and the pathogenesis of trx1 high expressing H. pylori remain still unknown. MATERIALS AND METHODS We investigated the expression level of H. pylori trx1 and H. pylori rocF in human gastric antrum tissues using reverse transcription and quantitative real-time PCR (RT-qPCR) and clarified the clinical application value of trx1 and rocF for screening highly pathogenic H. pylori. The pathogenic mechanism of Trx1 were further explored by RNA-seq of GES-1 cells co-cultured with trx1 high or low expressing H. pylori. Differentially expressed genes and signaling pathways were validated by RT-qPCR, Enzyme-linked immunosorbent assay (ELISA), western blot, immunohistochemistry and immunofluorescence. We also assessed the adherence of trx1 high and low expressing H. pylori to GES-1 cells. RESULTS We found that H. pylori trx1 and H. pylori rocF were more significantly expressed in the gastric cancer and peptic ulcer group than that in the gastritis group and the parallel diagnosis of H. pylori trx1 and H. pylori rocF had high sensitivity. The trx1 high expressing H. pylori had stronger adhesion ability to GES-1 cells and upregulated the interleukin (IL) 23A/nuclear factor κappaB (NF-κB)/IL17A, IL6, IL8 pathway. CONCLUSIONS H. pylori trx1 and H. pylori rocF can be used in clinical screening of highly pathogenic H. pylori and predicting the outcome of H. pylori infection. The trx1 high expressing H. pylori has stronger adhesion capacity and promotes the development of gastric diseases by upregulating the activation of NF-κB signaling pathway.
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Affiliation(s)
- Xin Guan
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jing Ning
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Weiwei Fu
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ye Wang
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jing Zhang
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Shigang Ding
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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Amalia R, Vidyani A, I’tishom R, Efendi WI, Danardono E, Wibowo BP, Parewangi ML, Miftahussurur M, Malaty HM. The Prevalence, Etiology and Treatment of Gastroduodenal Ulcers and Perforation: A Systematic Review. J Clin Med 2024; 13:1063. [PMID: 38398375 PMCID: PMC10888557 DOI: 10.3390/jcm13041063] [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: 12/05/2023] [Revised: 01/31/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
(1) Background: Gastroduodenal perforation (GDP) is a life-threatening condition caused by a spontaneous or traumatic event. Treatment should be based on the mechanism of damage, timing, location, extent of the injury, and the patient's clinical condition. We aimed to examine several etiologic factors associated with gastroduodenal perforation and to search for the best method(s) for its prevention and treatment. (2) Methods: We conducted extensive literature reviews by searching numerous studies obtained from PubMed, Science Direct, and Cochrane for the following keywords: gastroduodenal perforation, Helicobacter pylori, NSAIDs' use, side effects of GDP, laparoscopy, and surgery. The primary outcome was the reported occurrence of GDP. (3) Results: Using keywords, 883 articles were identified. After applying the inclusion and exclusion criteria, 53 studies were eligible for the current analyses, with a total number of 34,692 gastroduodenal perforation cases. Even though the risk factors of gastroduodenal perforation are various, the prevalence of H. pylori among patients with perforation is considerably high. As technology develops, the treatment for gastric perforation will also improve, with laparoscopic surgery having a lower mortality and complication rate compared to open surgery for GDP treatment. (4) Conclusions: H. pylori infection plays the most significant role in GDP, more than NSAIDs, surgery, chemotherapy, or transplantation. Treatment of H. pylori infection is essential to decrease the prevalence of GDP and speed up its recovery. However, urgent cases require immediate intervention, such as laparoscopic or open surgery.
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Affiliation(s)
- Rizki Amalia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu 879-5593, Japan;
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Amie Vidyani
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Reny I’tishom
- Department of Medical Biology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia;
| | - Wiwin Is Efendi
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia;
| | - Edwin Danardono
- Department of Surgery, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia;
| | - Bogi Pratomo Wibowo
- Department of Endocrinology, Saiful Anwar General Hospital, Malang 65111, Indonesia;
| | - Muhammad Lutfi Parewangi
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia;
| | - Muhammad Miftahussurur
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia;
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Hoda M. Malaty
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60115, Indonesia
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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Jarzab M, Skorko-Glonek J. There Are No Insurmountable Barriers: Passage of the Helicobacter pylori VacA Toxin from Bacterial Cytoplasm to Eukaryotic Cell Organelle. MEMBRANES 2023; 14:11. [PMID: 38248700 PMCID: PMC10821523 DOI: 10.3390/membranes14010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/23/2024]
Abstract
The Gram-negative bacterium Helicobacter pylori is a very successful pathogen, one of the most commonly identified causes of bacterial infections in humans worldwide. H. pylori produces several virulence factors that contribute to its persistence in the hostile host habitat and to its pathogenicity. The most extensively studied are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA). VacA is present in almost all H. pylori strains. As a secreted multifunctional toxin, it assists bacterial colonization, survival, and proliferation during long-lasting infections. To exert its effect on gastric epithelium and other cell types, VacA undergoes several modifications and crosses multiple membrane barriers. Once inside the gastric epithelial cell, VacA disrupts many cellular-signaling pathways and processes, leading mainly to changes in the efflux of various ions, the depolarization of membrane potential, and perturbations in endocytic trafficking and mitochondrial function. The most notable effect of VacA is the formation of vacuole-like structures, which may lead to apoptosis. This review focuses on the processes involved in VacA secretion, processing, and entry into host cells, with a particular emphasis on the interaction of the mature toxin with host membranes and the formation of transmembrane pores.
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Affiliation(s)
| | - Joanna Skorko-Glonek
- Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland;
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Motamedi H, Abiri R, Salari F, Jalili C, Alvandi A. Reduction of UreB and CagA expression level by siRNA construct in Helicobacter pylori strain SS1. BMC Microbiol 2023; 23:401. [PMID: 38114907 PMCID: PMC10729366 DOI: 10.1186/s12866-023-03143-x] [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: 06/05/2023] [Accepted: 12/05/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Two important virulence factors, urease and cagA, play an important role in Helicobacter pylori (H. pylori) gastric cancer. Aim of this study was to investigate the expression level and function of ureB and cagA using small interfering RNAs (siRNA). METHODS SS1 strain of H. pylori was considered as host for natural transformation. siRNA designed for ureB and cagA genes were inserted in pGPU6/GFP/Neo siRNA plasmid vector to evaluate using phenotypic and genotypic approaches. Then, qPCR was performed for determining inhibition rate of ureB and cagA gene expression. RESULTS The expression levels of siRNA-ureB and siRNA-cagA in the recombinant strain SS1 were reduced by about 5000 and 1000 fold, respectively, compared to the native H. pylori strain SS1. Also, preliminary evaluation of siRNA-ureB in vitro showed inhibition of urea enzyme activity. These data suggest that siRNA may be a powerful new tool for gene silencing in vitro, and for the development of RNAi-based anti-H. pylori therapies. CONCLUSION Our results show that targeting ureB and cagA genes with siRNA seems to be a new strategy to inhibit urease enzyme activity, reduce inflammation and colonization rate.
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Affiliation(s)
- Hamid Motamedi
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ramin Abiri
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farhad Salari
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Cyrus Jalili
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amirhoushang Alvandi
- Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Pernigoni N, Guo C, Gallagher L, Yuan W, Colucci M, Troiani M, Liu L, Maraccani L, Guccini I, Migliorini D, de Bono J, Alimonti A. The potential role of the microbiota in prostate cancer pathogenesis and treatment. Nat Rev Urol 2023; 20:706-718. [PMID: 37491512 DOI: 10.1038/s41585-023-00795-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2023] [Indexed: 07/27/2023]
Abstract
The human body hosts a complex and dynamic population of trillions of microorganisms - the microbiota - which influences the body in homeostasis and disease, including cancer. Several epidemiological studies have associated specific urinary and gut microbial species with increased risk of prostate cancer; however, causal mechanistic data remain elusive. Studies have associated bacterial generation of genotoxins with the occurrence of TMPRSS2-ERG gene fusions, a common, early oncogenic event during prostate carcinogenesis. A subsequent study demonstrated the role of the gut microbiota in prostate cancer endocrine resistance, which occurs, at least partially, through the generation of androgenic steroids fuelling oncogenic signalling via the androgen receptor. These studies present mechanistic evidence of how the host microbiota might be implicated in prostate carcinogenesis and tumour progression. Importantly, these findings also reveal potential avenues for the detection and treatment of prostate cancer through the profiling and modulation of the host microbiota. The latter could involve approaches such as the use of faecal microbiota transplantation, prebiotics, probiotics, postbiotics or antibiotics, which can be used independently or combined with existing treatments to reverse therapeutic resistance and improve clinical outcomes in patients with prostate cancer.
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Affiliation(s)
- Nicolò Pernigoni
- Institute of Oncology Research, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Christina Guo
- Institute of Cancer Research, London, UK
- Royal Marsden Hospital, London, UK
| | | | - Wei Yuan
- Institute of Cancer Research, London, UK
| | - Manuel Colucci
- Institute of Oncology Research, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Martina Troiani
- Institute of Oncology Research, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Lei Liu
- Institute of Oncology Research, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Luisa Maraccani
- Institute of Oncology Research, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
- Veneto Institute of Molecular Medicine, Padova, Italy
| | - Ilaria Guccini
- Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
| | - Denis Migliorini
- Department of Oncology, Geneva University Hospitals, Geneva, Switzerland
- Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland
- Swiss Cancer Center Léman, Lausanne and Geneva, Geneva, Switzerland
- AGORA Cancer Research Center, Lausanne, Switzerland
| | - Johann de Bono
- Institute of Cancer Research, London, UK
- Royal Marsden Hospital, London, UK
| | - Andrea Alimonti
- Institute of Oncology Research, Bellinzona, Switzerland.
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
- Veneto Institute of Molecular Medicine, Padova, Italy.
- Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
- Department of Medicine, University of Padova, Padova, Italy.
- Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
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Buyuk F, Karakaya E, Akar M, Kayman T, Tarhane S, Ozcan HE, Celebi O, Saticioglu IB, Anuk T, Abay S, Otlu S, Aydin F. A comprehensive study of Helicobacter pylori infection: molecular analysis, antibacterial susceptibility, and histopathological examination. Antonie Van Leeuwenhoek 2023; 116:1261-1273. [PMID: 37603113 DOI: 10.1007/s10482-023-01868-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 08/07/2023] [Indexed: 08/22/2023]
Abstract
Helicobacter pylori is a pathogen associated with gastroduodenal diseases. This study aimed; (i) to investigate H. pylori presence by invasive tests in adult dyspeptic patients, (ii) to determine antibiotic susceptibility and genotypic characteristics of the H. pylori isolates, and (iii) to investigate the relationship between the H. pylori genotypes and the histopathological findings. In this cross-sectional study, gastric biopsy samples from 208 adult dyspeptic patients were used for culture, tissue Polymerase Chain Reaction (PCR), and histopathological analysis. Antibiotic susceptibility of the H. pylori isolates was analyzed by gradient method. Analysis of the virulence genes was performed by monoplex PCR. Genetic profiles (from A to H) were created based on the virulence genes presence. Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR) was used for the genotyping of the H. pylori isolates. The mean age of the patients was 46 (± 15) years and 128 (61.5%) of them were female. H. pylori positivity was detected by culture, tissue PCR and histopathological examination in 59 (28.4%), 114 (54.8%) and 81 (38.9%) patients, respectively. The overall prevalence of H. pylori was found to be 63% (131/208). All H. pylori isolates were susceptible to tetracycline and amoxicillin. The resistance rates for metronidazole, clarithromycin, levofloxacin, and rifampicin were 67.2%, 27.9%, 34.4% and 13.11%, respectively. Multi drug resistance (MDR) was detected at the rate of 45.9% (28/61). While the most common virulence gene was cagA (93.44%), the least common was vacAm1 (23%). The predominant genetic profile was profile A (47.5%). ERIC-PCR results revealed a total of 26 different patterns. A high prevalence of H. pylori was detected in adult dyspeptic patients as in developing countries. It was observed significant genotypic heterogeneity and virulence gene diversity within the isolates. A considerable resistance rate detected against antibiotics such as clarithromycin, metronidazole, and levofloxacin, which are frequently used in the eradication of H. pylori, should be taken into consideration when creating regional empirical treatment regimens.
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Affiliation(s)
- Fatih Buyuk
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye.
| | - Emre Karakaya
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
| | - Mustafa Akar
- Department of Gastroenterology, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Türkiye
| | - Tuba Kayman
- Department of Medical Microbiology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Türkiye
| | - Serdal Tarhane
- Veterinary Department, Eldivan Vocational School of Health Services, Çankırı Karatekin University, Çankırı, Türkiye
| | - Hacer Ece Ozcan
- Department of Medical Pathology, Mersin City Hospital, Mersin, Türkiye
| | - Ozgur Celebi
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye
| | - Izzet Burcin Saticioglu
- Department of Aquatic Animal Diseases, Faculty of Veterinary Medicine, Uludağ University, Bursa, Türkiye
| | - Turgut Anuk
- Department of General Surgery, Erzurum Faculty of Medicine, University of Health Sciences, Erzurum, Türkiye
| | - Secil Abay
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
| | - Salih Otlu
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye
| | - Fuat Aydin
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
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Fatima A, Ibrahim M, Naseer A, Pervez A, Asad M, Shah AA, Hasan F, Alonazi WB, Ferheen I, Khan S. Identification, Genome Sequencing, and Characterizations of Helicobacter pylori Sourced from Pakistan. Microorganisms 2023; 11:2658. [PMID: 38004670 PMCID: PMC10673187 DOI: 10.3390/microorganisms11112658] [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: 09/24/2023] [Revised: 10/19/2023] [Accepted: 10/28/2023] [Indexed: 11/26/2023] Open
Abstract
The stomach's colonization by Helicobacter pylori (H. pylori) results in gastritis, ulcers, and stomach cancer. Frequently, pain is treated with medication, but resistant H. pylori infections are not. Therefore, it is important to find pharmacological targets and improved treatments for resistant H. pylori strains. The aim of the current study was sampling, identification, drug susceptibility testing following genome sequencing and comparative genome-wide analysis of selected H. pylori strains from Pakistan with three representative strains for virulence and drug-resistant characteristics. Based on culture, biochemistry, and molecular biology, 84 strains of H. pylori were identified, which made up 47% of the enrolled cases. Among all H. pylori strains, the highest resistance was reported for metronidazole with 82 H. pylori strains (98%), followed by clarithromycin with 62 resistant strains (74%). Among metronidazole-resistant strains, 38 strains (46%) were also resistant to clarithromycin, contributing 61% of clarithromycin resistant cases. Two strains, HPA1 and HPA2, isolated from 'gastritis' and 'gastric ulcer' patients, respectively, were further processed for WGS. The draft genome sequences of H. pylori strains HPA1 and HPA2 encode 1.66 Mbp and 1.67 Mbp genome size, 24 and 4 contiguous DNA sequences, and 1650 and 1625 coding sequences, respectively. Both the genomes showed greater than 90% similarity with the reference strain H. pylori ATCC 43504/PMSS1. The antibiotic-resistant genes were identified among all the strains with overall similarity above 95%, with minor differences in the sequence similarity. Using the virulent gene data obtained from the Virulence Factor Database, 75 to 85 virulent genes were identified in the five genome assemblies with various key genes such as cytolethal distending toxin (cdt), type IV secretion system, cag PAI, plasticity region, cell-motility- and flagellar-associated genes, neutrophil-activating protein (HP-NAP), T4SS effector cytotoxin-associated gene A (cagA), and urease-associated genes ureA and ureB, etc. Sequence similarity between the virulence factors found in this study and reference genes was at least 90%. In summary, the results of our study showed the relationship between clinical results and specific H. pylori strains' (HPA1 and HPA2) genetics such as antibiotic resistance and specific virulence factors. These findings provide valued understanding of the epidemiology of H. pylori-associated diseases. Moreover, identification and genomics analysis have provided insights into the epidemiology, genetic diversity, pathogenicity, and potential drug resistance genes of H. pylori strains, offering a foundation for developing more targeted and effective medical interventions, including anti-virulent medications.
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Affiliation(s)
- Anees Fatima
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
- Department of Microbiology, Faculty of Health & Biological Sciences, Abbottabad University of Science & Technology, Abbottabad 22500, Pakistan
| | - Muhammad Ibrahim
- Department of Biosciences, COMSATS University Islamabad (CUI), Sahiwal Campus, Sahiwal 55000, Pakistan (M.A.)
| | - Adil Naseer
- Department of Gastroenterology, Ayub Medical College, Main Mansehra Road, Abbottabad 22020, Pakistan;
| | - Arshid Pervez
- Department of Environmental Sciences, COMSATS University Islamabad (CUI), Abbottabad Campus, University Road, Tobe Camp, Abbottabad 22010, Pakistan;
| | - Muhammad Asad
- Department of Biosciences, COMSATS University Islamabad (CUI), Sahiwal Campus, Sahiwal 55000, Pakistan (M.A.)
| | - Aamer Ali Shah
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
| | - Fariha Hasan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
| | - Wadi B. Alonazi
- Health Administration Department, College of Business Administration, King Saud University, Riyadh 11587, Saudi Arabia;
| | - Ifra Ferheen
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy;
| | - Samiullah Khan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
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Aramouni K, Assaf RK, Azar M, Jabbour K, Shaito A, Sahebkar A, Eid AA, Rizzo M, Eid AH. Infection with Helicobacter pylori may predispose to atherosclerosis: role of inflammation and thickening of intima-media of carotid arteries. Front Pharmacol 2023; 14:1285754. [PMID: 37900161 PMCID: PMC10611526 DOI: 10.3389/fphar.2023.1285754] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Atherosclerosis is a major instigator of cardiovascular disease (CVD) and a main cause of global morbidity and mortality. The high prevalence of CVD calls for urgent attention to possible preventive measures in order to curb its incidence. Traditional risk factors of atherosclerosis, like age, smoking, diabetes mellitus, dyslipidemia, hypertension and chronic inflammation, are under extensive investigation. However, these only account for around 50% of the etiology of atherosclerosis, mandating a search for different or overlooked risk factors. In this regard, chronic infections, by Helicobacter pylori for instance, are a primary candidate. H. pylori colonizes the gut and contributes to several gastrointestinal diseases, but, recently, the potential involvement of this bacterium in extra-gastric diseases including CVD has been under the spotlight. Indeed, H. pylori infection appears to stimulate foam cell formation as well as chronic immune responses that could upregulate key inflammatory mediators including cytokines, C-reactive protein, and lipoproteins. These factors are involved in the thickening of intima-media of carotid arteries (CIMT), a hallmark of atherosclerosis. Interestingly, H. pylori infection was found to increase (CIMT), which along with other evidence, could implicate H. pylori in the pathogenesis of atherosclerosis. Nevertheless, the involvement of H. pylori in CVD and atherosclerosis remains controversial as several studies report no connection between H. pylori and atherosclerosis. This review examines and critically discusses the evidence that argues for a potential role of this bacterium in atherogenesis. However, additional basic and clinical research studies are warranted to convincingly establish the association between H. pylori and atherosclerosis.
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Affiliation(s)
- Karl Aramouni
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Roland K. Assaf
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Maria Azar
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Karen Jabbour
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Abdullah Shaito
- Biomedical Research Center, Department of Biomedical Sciences at College of Health Sciences, College of Medicine, Qatar University, Doha, Qatar
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Applied Biomedical Research Center, Department of Biotechnology, School of Pharmacy, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Assaad A. Eid
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Ali H. Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
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Saeed MK, Al-Ofairi BA, Hassan MA, Al-Jahrani MA, Abdulkareem AM. The clinical significance of some serum tumor markers among chronic patients with Helicobacter pylori infections in Ibb Governorate, Yemen. Infect Agent Cancer 2023; 18:60. [PMID: 37828556 PMCID: PMC10571253 DOI: 10.1186/s13027-023-00542-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/02/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a carcinogenic bacterium, it is the greatest risk factor for gastric cancer (GC), according to these evidences, there may be a certain association between chronic H. pylori infections and serum levels of tumor markers. This study was conducted to determine serum levels of some tumor markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and cancer antigen 72-4 (CA72-4) in patients with chronic H. pylori infections and evaluate the association between serum tumor marker levels and chronic patients with H. pylori infections in Ibb Governorate, Yemen. SUBJECTS AND METHODS This study involved 200 patients who had been diagnosed with H. pylori infections using a serum immunochromatography antibody test. Stool and blood samples were collected from all patients to confirm the presence of H. pylori through detection of serum H. pylori IgG antibody and stool antigen test (SAT). Additionally, serum samples were analyzed to measurement the level of certain tumor markers CEA, CA19-9 and CA72-4. These tests were conducted at various Hospitals, Gastroenterology and Hepatology clinics in Ibb governorate, Yemen from October 2019 to November 2020. RESULTS The findings of current study showed that the prevalence of H. pylori infections by rapid anti H. pylori test were 200 (100%), 157 (78.5%) by serum H. pylori IgG antibody and 108 (54%) by SAT. In addition, the results showed that 42 (21%) of the patients had abnormal level of CEA, 30 (15%) had abnormal level of CA19-9 and 31 (15.5%) had abnormal level of CA72-4. Most importantly, the results indicated that the serum tumor marker levels CEA, CA19-9 and CA72-4 were correlated with the levels of serum H. pylori IgG antibody as well as positive results from the SAT (P < 0.05). Furthermore, the results indicated that serum tumor marker levels were associated with different infection status. Finally, the results indicated that the serum levels of tumor markers were associated with older ages, symptomatic patients and long duration of H. pylori infections (P < 0.05). CONCLUSION The findings of this study indicated that there is a significant association between chronic H. pylori infections and the serum levels of tumor markers (CEA, CA19-9 and CA72-4). This suggests that the patients with active chronic H. pylori infection may have an increased risk of developing GC. Therefore, monitoring and early detection of H. pylori infection and tumor markers levels in these patients may be crucial for identifying individuals at higher risk and implementing appropriate interventions.
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Affiliation(s)
- Marwan K Saeed
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen.
- Department of Medical Laboratories, University of Science and Technology, Ibb, Yemen.
| | - B A Al-Ofairi
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
- Departement of Medical Laboratory, Faculty of Medical Sciences, Queen Arwa University, Sana'a, Yemen
| | - Mohammed A Hassan
- Pathology Department, Faculty of Medicine, Taiz University, Taiz, Yemen
| | - M A Al-Jahrani
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
| | - Ahmed M Abdulkareem
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
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Shegefti S, Bolori S, Nabavi-Rad A, Dabiri H, Yadegar A, Baghaei K. Helicobacter pylori-derived outer membrane vesicles suppress liver autophagy: A novel mechanism for H. pylori-mediated hepatic disorder. Microb Pathog 2023; 183:106319. [PMID: 37619914 DOI: 10.1016/j.micpath.2023.106319] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Helicobacter pylori outer membrane vesicles (OMVs) are nano-sized structures, which have been recently suggested to play a crucial role in H. pylori pathogenesis. There are growing evidence indicating the relationship of H. pylori infection with extra-gastroduodenal diseases, especially liver-related disorders. This study was aimed to investigate the effects of H. pylori-derived OMVs on autophagy in hepatic stellate cells (HSCs). MATERIAL AND METHODS A selection of five clinical strains of H. pylori with different virulence genotypes were included. The OMVs were isolated by ultracentrifugation and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The protein concentration of OMVs was measured by BCA assay. MTT assay was used to determine the viability of LX-2 cells (human HSCs) treated with OMVs. The expression level of MTOR, AKT, PI3K, BECN1, ATG16 and LC3B genes was assessed in OMVs-treated LX-2 cells using quantitative real-time PCR. Moreover, immunocytochemistry was performed to evaluate the protein expression of MTOR and LC3B autophagy markers. RESULTS H. pylori strains produced round shape nano-vesicles ranging from 50 to 500 nm. Treatment of HSCs with H. pylori-derived OMVs at concentration of 10 μg/mL for 24 h significantly elevated the expression of autophagy inhibitory markers (PI3K, AKT, and MTOR) and suppressed the mRNA expression level of autophagy core proteins (BECN1, ATG16 and LC3B). Immunocytochemistry also presented a substantial reduction in the concentration of LC3B autophagy core protein, and a marked elevation in the amount of MTOR autophagy inhibitory protein. CONCLUSION This study revealed that H. pylori-derived OMVs could potentially suppress autophagy flux in HSCs as a novel mechanism for H. pylori-mediated liver autophagy impairment and liver disease development. Further studies are required to elucidate the exact role of OMV-carried contents in liver autophagy, and liver-associated disorders.
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Affiliation(s)
- Saina Shegefti
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahin Bolori
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Microbiology Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Kaveh Baghaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Juntarachot N, Sunpaweravong S, Kaewdech A, Wongsuwanlert M, Ruangsri P, Pahumunto N, Teanpaisan R. Characterization of adhesion, anti-adhesion, co-aggregation, and hydrophobicity of Helicobacter pylori and probiotic strains. J Taibah Univ Med Sci 2023; 18:1048-1054. [PMID: 36969318 PMCID: PMC10031481 DOI: 10.1016/j.jtumed.2023.02.017] [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: 10/20/2022] [Revised: 01/09/2023] [Accepted: 02/27/2023] [Indexed: 03/12/2023] Open
Abstract
OBJECTIVES To characterize the adhesion ability of nine Helicobacter pylori strains and eight probiotics in human oral keratinocyte cells (H357 cells) in comparison to intestinal cells (Caco-2 and HIEC-6 cells). Subsequently, the anti-adhesion and co-aggregation abilities of the selected probiotic strains on H. pylori strains were investigated. METHODS Nine H. pylori strains, including H. pylori ATCC43504 (type strain), and 8 clinical strains, were isolated from oral samples of three patients (one non-disease, one gastritis patient, and one gastric cancer patient). Eight selected probiotic strains were used, as follows: Lacticaseibacillus paracasei SD1, Lacticaseibacillus rhamnosus SD4, L. rhamnosus SD11, Limosilactobacillus fermentum SD7, L. rhamnosus GG, Limosilactobacillus reuteri ATCC-PTA6475, Lacticaseibacillus casei Shirota, and L. paracasei CNCM I-1572. The adhesion and anti-adhesion abilities of H. pylori and the probiotic strains were investigated in H357, Caco-2, and HIEC-6 cells. Co-aggregation at various pHs, hydrophobicity, and surface receptors of the cell lines for H. pylori strains were examined. RESULTS All probiotic and H. pylori strains adhered to H357 significantly better than Caco-2, and HIEC-6 cells. Three probiotic strains (SD7, SD4, SD11) showed significantly higher adhesion than others. Of the clinical H. pylori strains, isolates from a gastric cancer patient had the highest adhesion ability to all of the cell lines tested. Probiotic strains that exhibited high adhesion ability provided high anti-adhesion and co-aggregation against H. pylori strains. Acidic conditions encouraged the co-aggregation of probiotics to H. pylori strains. CONCLUSION This study provides information relating to the adhesion abilities of clinical H. pylori and probiotic strains to the oral mucosa when compared to the intestinal mucosa. Certain probiotic strains may be useful for the successful eradication of H. pylori infection via anti-adhesion and co-aggregation.
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Affiliation(s)
- Nucharee Juntarachot
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Somkiat Sunpaweravong
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Mutita Wongsuwanlert
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Praphansri Ruangsri
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Nuntiya Pahumunto
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
- Department of Oral Diagnostic Sciences, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
| | - Rawee Teanpaisan
- Research Center of Excellence for Oral Health, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand
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Chen S, Shen W, Liu Y, Dong Q, Shi Y. Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial. Chin Med J (Engl) 2023; 136:1690-1698. [PMID: 37469024 DOI: 10.1097/cm9.0000000000002696] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.
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Affiliation(s)
- Shasha Chen
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Weina Shen
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Yuhuan Liu
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Qiang Dong
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China
| | - Yongquan Shi
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China
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Acosta-Astaiza C, López-Sandoval A, Bonilla-Chaves J, Valdes-Valdes A, Romo-Romero W. Helicobacter pylori virulence genotypes and their relationship with precursor lesions of gastric malignancy and histological parameters in infected patients in Colombia. Rev Peru Med Exp Salud Publica 2023; 40:348-353. [PMID: 37991039 PMCID: PMC10953661 DOI: 10.17843/rpmesp.2023.403.12858] [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: 05/05/2023] [Accepted: 09/13/2023] [Indexed: 11/23/2023] Open
Abstract
The aim of this research was to determine the presence of Helicobacter pylori virulence genotypes and their association with precursor lesions of gastric malignancy and histological parameters in patients with dyspepsia symptoms in southwestern Colombia. Polymerase chain reaction (PCR) was used for the genetic characterization of vacA, cagA, babA2 and sabA. The chi-square or Fischer test were used to evaluate the association between each genotype and the clinical outcome. We found that 86.3% of the patients with precursor lesions of gastric malignancy presented the vacA s1/m1 genotype, 68.1% had the cagA+ genotype and 68.8% and 55.8% had the babA2+ and sabA+ genotypes, respectively. Our results show association between virulence genotypes and severe degree of polymorphonuclear cell infiltration. In addition, we found an association between the combination of vacA/cagA, vacA/sabA and babA2/sabA genes. This study provides evidence about the association of H. pylori virulence genotypes and gastric inflammation in infected patients.
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Affiliation(s)
- Claudia Acosta-Astaiza
- Grupo de Investigación en Genética Humana Aplicada, Universidad del Cauca, Popayán, Colombia
| | - Alexis López-Sandoval
- Grupo de Investigación en Genética Humana Aplicada, Universidad del Cauca, Popayán, Colombia
| | - Juan Bonilla-Chaves
- Grupo de Investigación en Genética Humana Aplicada, Universidad del Cauca, Popayán, Colombia
| | - Anyi Valdes-Valdes
- Grupo de Investigación en Genética Humana Aplicada, Universidad del Cauca, Popayán, Colombia
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Zhou X, Zhu Y, Liu J, Liu J. Effects of Helicobacter pylori Infection on the Development of Chronic Gastritis. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2023; 34:700-713. [PMID: 37249580 PMCID: PMC10441145 DOI: 10.5152/tjg.2023.22316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 09/25/2022] [Indexed: 05/31/2023]
Abstract
BACKGROUND/AIMS Based on the gene expression profiles of gastric epithelial tissue at different stages of Helicobacter pylori-infected gastritis, key long noncoding RNAs and genes in the development of Helicobacter pylori infection-induced gastritis were screened to provide a basis for early diagnosis and treatment. MATERIALS AND METHODS We downloaded 2 sets of sample data from the database, including gastric epithelial tissue samples from gastritis patients from Bhutan and Dominican, and screened mRNAs in the differentially expressed RNAs of the 2 regions. Mfuzz clustering algorithm was used to screen RNAs related to the 3 stages of chronic gastritis. The competing endogenous RNA (ceRNA) regulation network was constructed, and the selected key RNAs were verified. Samples from Bhutan and Dominican were subdivided into the chronic gastritis/ normal comparison groups, and the differentially expressed RNAs were screened to obtain 1067 overlapping RNAs, containing 21 long noncoding RNAs and 1046 mRNAs. RESULTS Thirty-eight significant gene ontology functional nodes and 6 expression pattern clusters were obtained. Two ceRNA regulatory networks were constructed, and 4 shared miRNAs (hsa-miR-320b, hsa-miR-320c, hsa-miR-320d, and hsa-miR-155-5p) were obtained. Eleven important long noncoding RNAs (AFAP1-AS1, MIR155HG, LINC00472, and FAM201A) and mRNAs (CASP10, SLC26A2, TRIB1, BMP2K, SCAMP1, TNKS1BP1, and MBOAT2) regulated by these 4 miRNAs were obtained. These results indicated that Helicobacter pylori infection had a certain influence on the development of gastritis. CONCLUSIONS The 11 key RNAs can provide a target for the early diagnosis and treatment of chronic gastritis following Helicobacter pylori infection.
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Affiliation(s)
| | | | - Jiayu Liu
- Nantong Hospital to Nanjing University of Chinese Medicine, Nantong, Jiangsu, China
| | - Jindi Liu
- Nantong Hospital to Nanjing University of Chinese Medicine, Nantong, Jiangsu, China
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Romanescu M, Oprean C, Lombrea A, Badescu B, Teodor A, Constantin GD, Andor M, Folescu R, Muntean D, Danciu C, Dalleur O, Batrina SL, Cretu O, Buda VO. Current State of Knowledge Regarding WHO High Priority Pathogens-Resistance Mechanisms and Proposed Solutions through Candidates Such as Essential Oils: A Systematic Review. Int J Mol Sci 2023; 24:9727. [PMID: 37298678 PMCID: PMC10253476 DOI: 10.3390/ijms24119727] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/31/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023] Open
Abstract
Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs' in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required.
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Affiliation(s)
- Mirabela Romanescu
- Doctoral School, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.R.); (A.L.); (B.B.); (A.T.); (G.D.C.)
- Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.A.); (R.F.); (D.M.)
| | - Camelia Oprean
- Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
- OncoGen Centre, County Hospital ‘Pius Branzeu’, Blvd. Liviu Rebreanu 156, 300723 Timisoara, Romania
| | - Adelina Lombrea
- Doctoral School, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.R.); (A.L.); (B.B.); (A.T.); (G.D.C.)
| | - Bianca Badescu
- Doctoral School, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.R.); (A.L.); (B.B.); (A.T.); (G.D.C.)
| | - Ana Teodor
- Doctoral School, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.R.); (A.L.); (B.B.); (A.T.); (G.D.C.)
| | - George D. Constantin
- Doctoral School, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.R.); (A.L.); (B.B.); (A.T.); (G.D.C.)
| | - Minodora Andor
- Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.A.); (R.F.); (D.M.)
| | - Roxana Folescu
- Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.A.); (R.F.); (D.M.)
| | - Delia Muntean
- Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.A.); (R.F.); (D.M.)
- Multidisciplinary Research Center on Antimicrobial Resistance, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Corina Danciu
- Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
- Research Center for Pharmaco-Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Olivia Dalleur
- Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Emmanuel Mounier 73, 1200 Brussels, Belgium
| | - Stefan Laurentiu Batrina
- Faculty of Agriculture, University of Life Sciences “King Mihai I” from Timisoara, Calea Aradului 119, 300645 Timisoara, Romania
| | - Octavian Cretu
- Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania; (M.A.); (R.F.); (D.M.)
| | - Valentina Oana Buda
- Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
- Research Center for Pharmaco-Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
- Ineu City Hospital, 2 Republicii Street, 315300 Ineu, Romania
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Reyes VE. Helicobacter pylori and Its Role in Gastric Cancer. Microorganisms 2023; 11:1312. [PMID: 37317287 PMCID: PMC10220541 DOI: 10.3390/microorganisms11051312] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/08/2023] [Accepted: 05/15/2023] [Indexed: 06/16/2023] Open
Abstract
Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and mitigating the burden of this life-threatening disease. This review aims to provide an overview of our current understanding of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.
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Affiliation(s)
- Victor E Reyes
- Department of Pediatrics and Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0372, USA
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Hassuna NA, Hussien SS, Abdelhakeem M, Aboalela A, Ahmed E, Abdelrahim SS. Regulatory B cells (Bregs) in Helicobacter pylori chronic infection. Helicobacter 2023; 28:e12951. [PMID: 36661205 DOI: 10.1111/hel.12951] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 01/01/2023] [Accepted: 01/04/2023] [Indexed: 01/21/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is linked with a wide variety of diseases and was reported in more than half of the world's population. Chronic H. pylori infection and its final clinical outcome depend mainly on the bacterial virulence factors and its ability to manipulate and adapt to human immune responses. Bregs blood levels have been correlated with increased bacterial load and infection chronicity, especially Gram-negative bacterial infection. This study aimed to identify prevalence and virulence factors of chronic H. pylori infection among symptomatic Egyptian patients and to examine its possible correlation to levels of regulatory B cells (Bregs) in blood. MATERIALS AND METHODS Gastric biopsies and blood samples from each of 113 adult patients, who underwent upper endoscopy, were examined for the detection of H. pylori by culture and PCR methods. Conventional PCR was used to determine various virulent genes prevalence and association to clinical outcome. Flow cytometry was used to evaluate Bregs levels. RESULTS Helicobacter pylori prevalence was 49.1% (55/112). Regarding virulence genes incidence, flaA gene was detected in 73% (40/55), vir B11 in 56.4% (31/55), hopZ1 in 34.5% (19/55), hopZ2 in 89% (49/55), babA2 in 52.7% (29/55), dupA jhp917 in 61.8% (34/55), vacA m1/m2 in 70.9% (39/55), and vacA s1/s2 in 69% (38/55) strains. Bregs levels were significantly lower in H. pylori-infected patients (p = 0.013), while total leukocyte count (TLC) showed no significant differences. CONCLUSION Helicobacter pylori infection prevalence was almost 49%, and the infection was found to be related to inflammatory conditions as gastritis and ulcers rather than malignant transformations. Also, we found that CD24+ CD38+ B cells were downregulated in H. pylori-infected patients.
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Affiliation(s)
- Noha A Hassuna
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Sahar Sh Hussien
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mohammed Abdelhakeem
- Clinical Pathology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | | | - Elham Ahmed
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Soha S Abdelrahim
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
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Luo Q, Liu N, Pu S, Zhuang Z, Gong H, Zhang D. A review on the research progress on non-pharmacological therapy of Helicobacter pylori. Front Microbiol 2023; 14:1134254. [PMID: 37007498 PMCID: PMC10063898 DOI: 10.3389/fmicb.2023.1134254] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 03/03/2023] [Indexed: 03/19/2023] Open
Abstract
Helicobacter pylori is a pathogenic microorganism that mainly resides in the human stomach and is the major cause of chronic gastritis, peptic ulcer and gastric cancer. Up to now, the treatment of Helicobacter pylori has been predominantly based on a combination of antibiotics and proton pump inhibitors. However, the increasing antibiotic resistance greatly limits the efficacy of anti-Helicobacter pylori treatment. Turning to non-antibiotic or non-pharmacological treatment is expected to solve this problem and may become a new strategy for treating Helicobacter pylori. In this review, we outline Helicobacter pylori's colonization and virulence mechanisms. Moreover, a series of non-pharmacological treatment methods for Helicobacter pylori and their mechanisms are carefully summarized, including probiotics, oxygen-rich environment or hyperbaric oxygen therapy, antibacterial photodynamic therapy, nanomaterials, antimicrobial peptide therapy, phage therapy and modified lysins. Finally, we provide a comprehensive overview of the challenges and perspectives in developing new medical technologies for treating Helicobacter pylori without drugs.
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Affiliation(s)
- Qian Luo
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Na Liu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Sugui Pu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Ze Zhuang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Hang Gong
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Dekui Zhang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
- Key Laboratory of Digestive Diseases, LanZhou University Second Hospital, Lanzhou, China
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Wattanawongdon W, Simawaranon Bartpho T, Tongtawee T. Relationship between Helicobacter pylori virulence genes and gastroduodenal disease. J Int Med Res 2023; 51:3000605231161465. [PMID: 36924226 PMCID: PMC10026102 DOI: 10.1177/03000605231161465] [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] [Indexed: 03/17/2023] Open
Abstract
OBJECTIVE This study aimed to identify Helicobacter pylori virulence factors and examine their associations with clinical outcomes in Thai patients. Moreover, the association between these genotypes and gastric mucosa morphological patterns was investigated. METHODS This retrospective study enrolled patients who underwent esophagogastroduodenoscopy at Suranaree University of Technology Hospital. The presence of the cagA and vacA genes was investigated by real-time polymerase chain reaction. RESULTS The H. pylori-specific genes ureA and 16S rRNA were detected in all 698 gastric biopsy specimens. In total, 567 (81.23%) patients with H. pylori infection were positive for the cagA gene, 443 (63.46%) were positive for the vacA gene, and 370 (53.0%) were positive for both. The cagA genotype was significantly more common in patients with chronic gastritis and peptic ulcers (78.99% and 79.41%, respectively) than the vacA gene (51.48% and 55.88%, respectively) and combined genotypes (32.34% and 47.05%, respectively). Moreover, the cagA genotype was significantly more common in patients with type 4 or 5 gastric mucosa patterns (69.49% and 76.31%, respectively). CONCLUSIONS The cagA genotype is the main cause of serious inflammation of the gastric mucosa. The cagA gene is possibly an important factor explaining gastroduodenal disease outcomes in Thai patients with H. pylori infection.
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Affiliation(s)
- Wareeporn Wattanawongdon
- School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Theeraya Simawaranon Bartpho
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- School of Pathology, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Taweesak Tongtawee
- School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
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Maghrabia AE, Elshebrawy HA, Mahros MA, Elgazzar MM, Sallam KI. Clarithromycin-, and metronidazole-resistant Helicobacter pylori isolated from raw and ready-to-eat meat in Mansoura, Egypt. Int J Food Microbiol 2023; 387:110052. [PMID: 36512933 DOI: 10.1016/j.ijfoodmicro.2022.110052] [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: 07/22/2022] [Revised: 11/20/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori), classified as a class-I carcinogen, is one of the leading medical pathogens of global concern associated mainly with the development of gastric adenocarcinomas and gastric mucosa-associated lymphoid tissue lymphomas; nevertheless, its prevalence in food especially meat and meat products is not fully covered. Additionally, the resistance of H. pylori towards clarithromycin is increasing worldwide and consider the leading cause of H. pylori treatment failure. Thus, the present study was designed to determine the prevalence, molecular characterization, and antimicrobial resistance profiles of clarithromycin-, and metronidazole-resistant H. pylori isolated from raw and ready-to-eat meat samples retailed in Mansoura city, Egypt. Among the 250 samples tested, H. pylori were molecularly confirmed in 40.8 % (49/120) of raw meat products and in 29.2 % (38/130) of ready-to-eat meat products. Precisely, 53.3 % (32/60), 56.7 % (17/30), 40 % (8/20), 55 % (11/20), 60 % (12/20), 13.3 % (4/30), and 15 % (3/20) of raw ground beef, beef burger, beef burger sandwiches, beef shawarma sandwiches, beef kofta sandwiches, beef luncheon, and beef sausage sandwiches, respectively were positive for H. pylori. Of the 204 biochemically-identified H. pylori isolates, 53.9 % (110/204) were molecularly confirmed by PCR through the detection of glmM, cagA, or vacA genes, which were detected at an incidence of 95.5 % (105/110), 77.3 % (85/110), and 20.9 % (23/110) among the isolates, respectively. The antimicrobial sensitivity testing revealed that all of the 110 (100 %) molecularly-confirmed H. pylori isolates were multidrug-resistant (MDR; resistant to four or more antibiotics). Interestingly, 100 % and 61.8 % of H. pylori isolated from raw and ready-to-eat meat were resistant to metronidazole and clarithromycin, respectively which consider alarming results as metronidazole and clarithromycin are the mainstay antibiotics in the treatment of H. pylori infections. Additionally, 94.5 %, 94.5 %, 24.5 %, 23.6 %, and 13.6 % of isolates were resistant to vancomycin, sulphamethoxazole-trimethoprim, imipenem, levofloxacin, and nitrofurantoin, respectively. The widespread contamination of examined raw and ready-to-eat meat product samples with MDR H. pylori isolates could constitute a tremendous public health hazard. Further studies concerning the prevalence and possible methods of elimination of H. pylori in different food categories distributed in the various provinces in Egypt as well as in other countries is required for a better understanding the H. pylori as an emerging foodborne pathogen.
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Affiliation(s)
- Aya Elsayed Maghrabia
- Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Hend Ali Elshebrawy
- Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mahmoud Ahmed Mahros
- Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohammed Mohammed Elgazzar
- Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Khalid Ibrahim Sallam
- Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
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Francis D, Bhairaddy A, Joy A, Hari GV, Francis A. Secretory proteins in the orchestration of microbial virulence: The curious case of Staphylococcus aureus. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 133:271-350. [PMID: 36707204 DOI: 10.1016/bs.apcsb.2022.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Microbial virulence showcases an excellent model for adaptive changes that enable an organism to survive and proliferate in a hostile environment and exploit host resources to its own benefit. In Staphylococcus aureus, an opportunistic pathogen of the human host, known for the diversity of the disease conditions it inflicts and the rapid evolution of antibiotic resistance, virulence is a consequence of having a highly plastic genome that is amenable to quick reprogramming and the ability to express a diverse arsenal of virulence factors. Virulence factors that are secreted to the host milieu effectively manipulate the host conditions to favor bacterial survival and growth. They assist in colonization, nutrient acquisition, immune evasion, and systemic spread. The structural and functional characteristics of the secreted virulence proteins have been shaped to assist S. aureus in thriving and disseminating effectively within the host environment and exploiting the host resources to its best benefit. With the aim of highlighting the importance of secreted virulence proteins in bacterial virulence, the present chapter provides a comprehensive account of the role of the major secreted proteins of S. aureus in orchestrating its virulence in the human host.
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Affiliation(s)
- Dileep Francis
- Department of Life Sciences, Kristu Jayanti College, Autonomous, Bengaluru, Karnataka, India.
| | - Anusha Bhairaddy
- Department of Life Sciences, Kristu Jayanti College, Autonomous, Bengaluru, Karnataka, India
| | - Atheene Joy
- Department of Life Sciences, Kristu Jayanti College, Autonomous, Bengaluru, Karnataka, India
| | | | - Ashik Francis
- Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
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