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Bektas N, Besic L, Kulo Cesic A, Marjanovic D, Prguda-Mujic J. The first study on population knowledge and attitudes regarding prevention, diagnostic methods, treatment, and recovery aspects related to Helicobacter pylori infection in Bosnia and Herzegovina. Front Public Health 2025; 13:1498407. [PMID: 40171422 PMCID: PMC11959088 DOI: 10.3389/fpubh.2025.1498407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 03/03/2025] [Indexed: 04/03/2025] Open
Abstract
The aim of this pioneering study was to examine the knowledge and attitudes regarding prevention, diagnostic methods, treatment, and recovery aspects related to Helicobacter pylori infection within the general population of Bosnia and Herzegovina (B&H). Study was conducted using the previously designed questionnaire, adapted for the B&H population. The research enrolled 1,031 participants, of whom 58.49% answered predominantly correctly to questions regarding Helicobacter pylori infectivity. Of all participants, 36.18% underwent screening, with 65.95% testing positive, and of those, 93.90% received treatment, mainly antibiotics (92.64%). Of those treated, 74.46% were re-tested and 30.23% of them had relapsed infection. Furthermore, the study identified lower infection rate in younger participants and, contraversaly, in participants with the history of long-term (lasting for more than a year) alcohol consumption, who were also shown to report symptoms' improvement post-treatment. Overall, B&H population demonstrated good knowledge toward Helicobacter pylori infection, with higher levels of knowledge in women, highly educated, or screened for H. pylori. Notably, participants expressed strong support for national Helicobacter pylori screening and thus underscored the importance of planning it in the public health initiatives in B&H. Also, due to the high relapsed infection rate, further effort needs to be directed toward education of risk groups i.e., older age groups, and community on effective measures for Helicobacter pylori prevention and treatment.
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Affiliation(s)
- Nejra Bektas
- Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina
| | - Larisa Besic
- Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina
| | - Aida Kulo Cesic
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Damir Marjanovic
- Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina
- Institute for Anthropological Research, Zagreb, Croatia
| | - Jasminka Prguda-Mujic
- Health Institute Biomedical Diagnostics and Research Medicover Diagnostics, Sarajevo, Bosnia and Herzegovina
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Isokpehi RD, Simmons SS, Makolo AU, Hollman AL, Adesida SA, Ojo OO, Abioye AO. Insights into Functions of Universal Stress Proteins Encoded by Genomes of Gastric Cancer Pathogen Helicobacter pylori and Related Bacteria. Pathogens 2025; 14:275. [PMID: 40137760 PMCID: PMC11944479 DOI: 10.3390/pathogens14030275] [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: 01/05/2025] [Revised: 03/09/2025] [Accepted: 03/11/2025] [Indexed: 03/29/2025] Open
Abstract
The genes that encode the universal stress protein (USP) family domain (pfam00582) aid the survival of bacteria in specific host or habitat-induced stress conditions. Genome sequencing revealed that the genome of Helicobacter pylori, a gastric cancer pathogen, typically contains one USP gene, while related helicobacters have one or two distinct USP genes. However, insights into the functions of Helicobacteraceae (Helicobacter and Wolinella) USP genes are still limited to inferences from large-scale genome sequencing. Thus, we have combined bioinformatics and visual analytics approaches to conduct a more comprehensive data investigation of a set of 1045 universal stress protein sequences encoded in 1014 genomes including 785 Helicobacter pylori genomes. The study generated a representative set of 183 USP sequences consisting of 180 Helicobacter sequences, two Wolinella succinogenes sequences, and a sequence from a related campylobacteria. We used the amino acid residues and positions of the 12 possible functional sites in 1030 sequences to identify 25 functional sites patterns for guiding studies on functional interactions of Helicobacteraceae USPs with ATP and other molecules. Genomic context searches and analysis identified USP genes of gastric and enterohepatic helicobacters that are adjacent or in operons with genes for proteins responsive to DNA-damaging oxidative stress (ATP-dependent proteases: ClpS and ClpA); and DNA uptake proteins (natural competence for transformation proteins: ComB6, ComB7, ComB8, ComB9, ComB10, ComBE, and conjugative transfer signal peptidase TraF). Since transcriptomic evidence indicates that oxidative stress and the presence of virulence-associated genes regulate the transcription of H. pylori USP gene, we recommend further research on Helicobacter USP genes and their neighboring genes in oxidative stress response and virulence of helicobacters. To facilitate the reuse of data and research, we produced interactive analytics resources of a dataset composed of values for variables including phylogeography of H. pylori strains, protein sequence features, and gene neighborhood.
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Affiliation(s)
- Raphael D. Isokpehi
- Transdisciplinary Data Scholars Development Program, Bethune-Cookman University, Daytona Beach, FL 32114, USA
| | - Shaneka S. Simmons
- Division of Arts and Sciences, Jarvis Christian University, Hawkins, TX 75765, USA
| | - Angela U. Makolo
- University of Ibadan Bioinformatics Group, Department of Computer Science, University of Ibadan, Ibadan 200005, Oyo State, Nigeria
| | | | - Solayide A. Adesida
- Department of Microbiology, Faculty of Science, University of Lagos, Akoka 101017, Lagos State, Nigeria
| | - Olabisi O. Ojo
- Department of Natural Sciences, Albany State University, Albany, GA 31721, USA
| | - Amos O. Abioye
- College of Pharmacy & Health Sciences, Belmont University, Nashville, TN 37212, USA;
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Huang AF, He C, Sheng JW, Jiang XT, Li NS, Fan HZ, Zhu Y. The epidemiological study of family-based Helicobacter pylori screening and its benefits: a cross-sectional study. Sci Rep 2025; 15:5553. [PMID: 39953078 PMCID: PMC11828999 DOI: 10.1038/s41598-025-87836-5] [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: 09/16/2024] [Accepted: 01/22/2025] [Indexed: 02/17/2025] Open
Abstract
This study aimed to manage Helicobacter pylori (H. pylori) infection through a family-centered approach. It conducted a two-year follow-up on infected individuals' family members in Yichun, Jiangxi, China, to gain comprehensive insights into the transmission dynamics, treatment adherence, and associated risk factors of H. pylori within households. A retrospective analysis was performed on the data obtained from households in Yichun City that participated in the nationwide multicenter H. pylori prevalence study in 2021, along with the corresponding subsequent follow-up data. The collected information encompassed fundamental demographic details of the families, their lifestyle patterns, and the status of H. pylori infection. Among 514 households, 222 comprised two individuals, whereas 68 constituted larger families with five or more members. All member was infected in 9.34% of households. Larger family sizes (≥ 5 individuals) and higher generational counts were closely associated with H. pylori infection (e.g., family size > 6: OR 4.46, 95%CI 1.29 to 15.46). Adult age, marital status, and household members' infections were identified as primary risk factors (e.g., married individuals: OR 2.03, 95%CI 1.56 to 2.65). Students and previously uninfected individuals exhibited lower infection risks (e.g., tested as negative: OR 0.48, 95%CI 0.31 to 0.73). Maternal, paternal, or sibling infections were linked to increased risks of child infections (e.g., mother infected: OR 2.58 95%CI 1.37 to 4.87). Successful eradication in ≥ 2 individuals reduced the infection risk for other members (OR 0.25, 95%CI (0.07 to 0.89). H. pylori displayed noticeable clustering infection characteristics within families. This study lends support to family-based management strategies, but given suboptimal adherence to household management, there is a need to enhance education on the hazards of H. pylori before implementing screening programs.
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Affiliation(s)
- Ao-Fei Huang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Wai zheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Cong He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Wai zheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Jian-Wen Sheng
- Department of Gastroenterology, Yichun Branch of Jiangxi Clinical Medical Research Center for Digestive Diseases, The People's Hospital of Yichun City, 1061 Jinxiu Avenue, Yuanzhou District, 336000, Yichun City, Jiangxi Province, China
| | - Xiao-Ting Jiang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Wai zheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Nian-Shuang Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Wai zheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Hui-Zhen Fan
- Department of Gastroenterology, Yichun Branch of Jiangxi Clinical Medical Research Center for Digestive Diseases, The People's Hospital of Yichun City, 1061 Jinxiu Avenue, Yuanzhou District, 336000, Yichun City, Jiangxi Province, China.
| | - Yin Zhu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Wai zheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China.
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Custodio M, Montalvo-Otivo R, Crispín-Ayala J, Bendezu-Meza J, Herrera-Quintana P, De la Cruz H, Huarcaya J. Occurrence of Helicobacter pylori in drinking water sources and antimicrobial resistance profile in the central region of Peru. Heliyon 2025; 11:e41533. [PMID: 39834420 PMCID: PMC11743314 DOI: 10.1016/j.heliyon.2024.e41533] [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: 07/30/2024] [Revised: 12/11/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Contamination of drinking water by Helicobacter pylori can cause serious diseases, including cancer. The determinants of the infection rate are socioeconomic status, low standard of living and overcrowding. In addition, exposure to environmental sources contaminated with feces, such as water and vegetables, is another risk factor for infection. We analyzed the occurrence of H. pylori in drinking water sources and the antimicrobial resistance profile in central Peru. Methods Water samples were collected from taps in four provinces of the Junín region. Previously, biofilm sampling was performed from the internal surface of the taps. The samples were cultured on modified brain heart infusion blood agar at 37 °C under microaerophilic conditions for seven days. Antibiotic sensitivity of H. pylori was determined by the Kirby Bauer diffusion method. Results The results revealed that pH (9.25) and turbidity (5.15 NTU) exceeded the Peruvian environmental quality standards for drinking water. The amount of free chlorine residual in the H. pylori positive water samples ranged from 0.02 to 0.12 mg/L. H. pylori was present in 2/192 tap water samples (1.04 %) and in 3/192 tap biofilm samples (1.56 %). It was observed that 100 % of H. pylori isolates from water samples from the Chilca district showed resistance to nalidixic acid and 66.67 % to both amoxicillin and chloramphenicol. Resistance to nalidixic acid of H. pylori isolates obtained from biofilm samples from taps in the El Tambo district ranged from 66.67 % to 100 %. Conclusion The study findings reveal that water samples and tap biofilms in the Chilca, El Tambo and Huamancaca chico districts in the Junín region harbor H. pylori. They also reveal variability in the pattern of resistance to more than one antibiotic tested from one district to another.
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Affiliation(s)
- María Custodio
- Facultad de Medicina Humana, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Raúl Montalvo-Otivo
- Facultad de Medicina Humana, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Jhonatan Crispín-Ayala
- Facultad de Medicina Humana, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Jeampier Bendezu-Meza
- Facultad de Medicina Humana, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Pilar Herrera-Quintana
- Facultad de Medicina Humana, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Heidi De la Cruz
- Laboratorio de Investigación de Aguas, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
| | - Javier Huarcaya
- Laboratorio de Investigación de Aguas, Universidad Nacional del Centro del Perú, Av. Mariscal Castilla N° 3989-4089, Huancayo, Peru
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Elbehiry A, Abalkhail A, Anajirih N, Alkhamisi F, Aldamegh M, Alramzi A, AlShaqi R, Alotaibi N, Aljuaid A, Alzahrani H, Alzaben F, Rawway M, Ibrahem M, Abdelsalam MH, Rizk NI, Mostafa MEA, Alfaqir MR, Edrees HM, Alqahtani M. Helicobacter pylori: Routes of Infection, Antimicrobial Resistance, and Alternative Therapies as a Means to Develop Infection Control. Diseases 2024; 12:311. [PMID: 39727641 PMCID: PMC11727528 DOI: 10.3390/diseases12120311] [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: 10/14/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 12/28/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the gastric epithelium and is associated with a range of gastrointestinal disorders, exhibiting a global prevalence of approximately 50%. Despite the availability of treatment options, H. pylori frequently reemerges and demonstrates increasing antibiotic resistance, which diminishes the efficacy of conventional therapies. Consequently, it is imperative to explore non-antibiotic treatment alternatives to mitigate the inappropriate use of antibiotics. This review examines H. pylori infection, encompassing transmission pathways, treatment modalities, antibiotic resistance, and eradication strategies. Additionally, it discusses alternative therapeutic approaches such as probiotics, anti-biofilm agents, phytotherapy, phototherapy, phage therapy, lactoferrin therapy, and vaccine development. These strategies aim to reduce antimicrobial resistance and enhance treatment outcomes for H. pylori infections. While alternative therapies can maintain low bacterial levels, they do not achieve complete eradication of H. pylori. These therapies are designed to bolster the immune response, minimize side effects, and provide gastroprotective benefits, rendering them suitable for adjunctive use alongside conventional treatments. Probiotics may serve as adjunctive therapy for H. pylori; however, their effectiveness as a monotherapy is limited. Photodynamic and phage therapies exhibit potential in targeting H. pylori infections, including those caused by drug-resistant strains, without the use of antibiotics. The development of a reliable vaccine is also critical for the eradication of H. pylori. This review identifies candidate antigens such as VacA, CagA, and HspA, along with various vaccine formulations, including vector-based and subunit vaccines. Some vaccines have demonstrated efficacy in clinical trials, while others have shown robust immune protection in preclinical studies. Nevertheless, each of the aforementioned alternative therapies requires thorough preclinical and clinical evaluation to ascertain their efficacy, side effects, cost-effectiveness, and patient compliance.
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Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia
| | - Nuha Anajirih
- Medical Emergency Services Department, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah P.O. Box 1109, Saudi Arabia
| | - Fahad Alkhamisi
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah 23311, Saudi Arabia
| | - Mohammed Aldamegh
- Pathology and Laboratory Medicine Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Abdullah Alramzi
- Medical Radiology Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Riyad AlShaqi
- Biomedical Engineer, Armed Forces Medical Services, Riyadh 12426, Saudi Arabia
| | - Naif Alotaibi
- Medical Hospital Administration Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Abdullah Aljuaid
- Medical Hospital Administration Department, Armed Forces Hospitals in Al Kharj, AL Kharj 16278, Saudi Arabia
| | - Hilal Alzahrani
- Physical Medicine and Rehabilitation Department, Armed Forces Center for Health Rehabilitation, Taif 21944, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah 23311, Saudi Arabia
| | - Mohammed Rawway
- Biology Department, College of Science, Jouf University, Sakaka 42421, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt
| | - Mai Ibrahem
- Department of Public Health, College of Applied Medical Science, King Khalid University, Abha 61421, Saudi Arabia
| | - Moustafa H. Abdelsalam
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Nermin I. Rizk
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Mohamed E. A. Mostafa
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Moneef Rohail Alfaqir
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Husam M. Edrees
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Mubarak Alqahtani
- Department of Radiology, King Fahd Armed Forces Hospital, Jeddah 23311, Saudi Arabia
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Fang Y, Jiang S, Zhou X, Zhou W, Jiang X, Chen L, Wang M, Chen Y, Li L. Whole-genome sequencing analyses and antibiotic resistance situation of 48 Helicobacter pylori strains isolated in Zhejiang, China. Gut Pathog 2024; 16:62. [PMID: 39444024 PMCID: PMC11515586 DOI: 10.1186/s13099-024-00656-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024] Open
Abstract
PURPOSE In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium. METHODS Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs). RESULTS The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977. CONCLUSION Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts.
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Affiliation(s)
- Yunhui Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
| | - Shiman Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Wangxiao Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China
| | - Xinrong Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China
| | - Lifeng Chen
- Department of Medical Engineering and Material Supplies, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Mengting Wang
- Zhejiang University of Finance & Economics, Hangzhou, Zhejiang Province, China
| | - Yunbo Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China.
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Elblihy AA, El-Ghannam S, Mohamed SZ, Hamouda MM, El-Ashry AH, Habib S. Helicobacter pylori-Toxoplasma gondii interplay with a possible role of IL-10. Acta Trop 2024; 253:107161. [PMID: 38417648 DOI: 10.1016/j.actatropica.2024.107161] [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: 12/20/2023] [Revised: 02/24/2024] [Accepted: 02/24/2024] [Indexed: 03/01/2024]
Abstract
Parasites are known for their modulatory effects on the immune response. The impact of toxoplasmosis on the immune response towards H. pylori is being studied in terms of IL-10 levels. This study included 110 patients suffering from persistent dyspepsia and 50 apparently healthy controls. Stool samples were collected and tested for H. pylori using colloidal gold one step test. Sera were examined for anti-Toxoplasma IgM and IgG using ELISA. IL-10 was also tested in the sera using ELISA. We found that Toxoplasma IgM and IgG tested positive in 1.8 % and 40 % of H. pylori positive patients, respectively. H. pylori-infected patients displayed higher IL-10 levels than the healthy controls (84 versus 0.59 pg/ml, respectively, P < 0.001). Classification of H. pylori positive patients according to Toxoplasma IgG titers yielded three groups: negative (58, 52.7 %), equivocal (8, 7.3 %), and positive (44, 40 %) groups, with the highest IL-10 levels detected in the double positive than the negative and the equivocal group (215 pg/ml versus 43 and 112.5 pg/ml, respectively, P < 0.001). There was strong positive correlation between Toxoplasma IgG titers and IL-10 levels (rs = 0.82, P < 0.001). Toxoplasma enhances IL-10 production in response to H. pylori infection. This could ameliorate the inflammatory response in the gastric mucosa, and subsequently more colonization with the H. pylori is achieved, resulting in persistent infection.
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Affiliation(s)
- Ayat A Elblihy
- Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Program of Medicine and surgery, Mansoura National University, Gamasa City, Egypt.
| | - Shreief El-Ghannam
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, New Damietta, Egypt
| | - Sherin Z Mohamed
- Department of Internal Medicine, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Marwa M Hamouda
- Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Amira H El-Ashry
- Department of Medical Microbiology and Immunology, Faculty of Medicine. Mansoura University, Mansoura, Egypt
| | - Samar Habib
- Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA, USA; DCG Center for Excellence in Research, Scholarship, and Innovation (CERSI), Augusta University, Augusta, GA, USA
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Smith SI, Schulz C, Ugiagbe R, Ndip R, Dieye Y, Leja M, Onyekwere C, Ndububa D, Ajayi A, Jolaiya TF, Jaka H, Setshedi M, Gunturu R, Otegbayo JA, Lahbabi-Amrani N, Arigbabu AO, Kayamba V, Nashidengo PA. Helicobacter pylori Diagnosis and Treatment in Africa: The First Lagos Consensus Statement of the African Helicobacter and Microbiota Study Group. Dig Dis 2024; 42:240-256. [PMID: 38493766 DOI: 10.1159/000537878] [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: 09/28/2023] [Accepted: 02/14/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.
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Affiliation(s)
- Stella I Smith
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Rose Ugiagbe
- Department of Medicine, University of Benin Teaching Hospital, Benin, Nigeria
| | - Roland Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Yakhya Dieye
- Pole of Microbiology, Institut Pasteur de Dakar, Dakar, Senegal
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Charles Onyekwere
- Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Nigeria
| | - Dennis Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - Abraham Ajayi
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | | | - Hyasinta Jaka
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Mashiko Setshedi
- Departments of Medicine, Division of Gastroenterology, University of Cape Town, Cape Town, South Africa
| | - Revathi Gunturu
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | | | - Naima Lahbabi-Amrani
- Faculty of Medicine and Pharmacy in Rabat, University Mohammed V, Rabat, Morocco
| | | | - Violet Kayamba
- Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia
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9
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Malfertheiner P, Camargo MC, El-Omar E, Liou JM, Peek R, Schulz C, Smith SI, Suerbaum S. Helicobacter pylori infection. Nat Rev Dis Primers 2023; 9:19. [PMID: 37081005 PMCID: PMC11558793 DOI: 10.1038/s41572-023-00431-8] [Citation(s) in RCA: 299] [Impact Index Per Article: 149.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/17/2023] [Indexed: 04/22/2023]
Abstract
Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
- Medical Department Klinik of Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke Universität, Magdeburg, Germany.
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Emad El-Omar
- Microbiome Research Centre, St George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Richard Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Stella I Smith
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria
| | - Sebastian Suerbaum
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany
- National Reference Center for Helicobacter pylori, Munich, Germany
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10
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Yamaoka Y, Saruuljavkhlan B, Alfaray RI, Linz B. Pathogenomics of Helicobacter pylori. Curr Top Microbiol Immunol 2023; 444:117-155. [PMID: 38231217 DOI: 10.1007/978-3-031-47331-9_5] [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: 01/18/2024]
Abstract
The human stomach bacterium Helicobacter pylori, the causative agent of gastritis, ulcers and adenocarcinoma, possesses very high genetic diversity. H. pylori has been associated with anatomically modern humans since their origins over 100,000 years ago and has co-evolved with its human host ever since. Predominantly intrafamilial and local transmission, along with genetic isolation, genetic drift, and selection have facilitated the development of distinct bacterial populations that are characteristic for large geographical areas. H. pylori utilizes a large arsenal of virulence and colonization factors to mediate the interaction with its host. Those include various adhesins, the vacuolating cytotoxin VacA, urease, serine protease HtrA, the cytotoxin-associated genes pathogenicity island (cagPAI)-encoded type-IV secretion system and its effector protein CagA, all of which contribute to disease development. While many pathogenicity-related factors are present in all strains, some belong to the auxiliary genome and are associated with specific phylogeographic populations. H. pylori is naturally competent for DNA uptake and recombination, and its genome evolution is driven by extraordinarily high recombination and mutation rates that are by far exceeding those in other bacteria. Comparative genome analyses revealed that adaptation of H. pylori to individual hosts is associated with strong selection for particular protein variants that facilitate immune evasion, especially in surface-exposed and in secreted virulence factors. Recent studies identified single-nucleotide polymorphisms (SNPs) in H. pylori that are associated with the development of severe gastric disease, including gastric cancer. Here, we review the current knowledge about the pathogenomics of H. pylori.
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Affiliation(s)
- Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Batsaikhan Saruuljavkhlan
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, 60286, East Java, Indonesia
| | - Bodo Linz
- Division of Microbiology, Department Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
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11
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Thorpe HA, Tourrette E, Yahara K, Vale FF, Liu S, Oleastro M, Alarcon T, Perets TT, Latifi-Navid S, Yamaoka Y, Martinez-Gonzalez B, Karayiannis I, Karamitros T, Sgouras DN, Elamin W, Pascoe B, Sheppard SK, Ronkainen J, Aro P, Engstrand L, Agreus L, Suerbaum S, Thorell K, Falush D. Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations. Nat Commun 2022; 13:6842. [PMID: 36369175 PMCID: PMC9652371 DOI: 10.1038/s41467-022-34475-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 10/26/2022] [Indexed: 11/13/2022] Open
Abstract
Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
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Affiliation(s)
- Harry A Thorpe
- Department of Biostatistics, University of Oslo, Oslo, Norway
| | - Elise Tourrette
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
| | - Koji Yahara
- Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Filipa F Vale
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Siqi Liu
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Mónica Oleastro
- National Reference Laboratory for Gastrointestinal Infections, Department of Infectious Diseases, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal
| | - Teresa Alarcon
- Department of Microbiology, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain
| | - Tsachi-Tsadok Perets
- Gastroenterology Laboratory, Rabin Medical Center, Petah Tikva, Israel
- Department of Digital Medical Technologies, Holon Institute of Technology, Holon, Israel
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Oita, Japan
- Department of Medicine-Gastroenterology, Baylor College of Medicine, Houston, TX, USA
| | | | - Ioannis Karayiannis
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece
| | | | | | - Wael Elamin
- G42 Healthcare, Abu Dhabi, UAE
- Elrazi University, Khartoum, Sudan
| | - Ben Pascoe
- Department of Biology, University of Oxford, Oxford, UK
| | - Samuel K Sheppard
- Ineos Oxford Institute, Department of Biology, University of Oxford, Oxford, UK
| | - Jukka Ronkainen
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
- Primary Health Care Center, Tornio, Finland
| | | | - Lars Engstrand
- Center for Translational Microbiome Research, Department for Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Lars Agreus
- Division of Family Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Sebastian Suerbaum
- Department of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer Institute, Faculty of Medicine, LMU Munich, Munich, Germany
- Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hanover, Germany
- DZIF German Center for Infection Research, Hannover-Braunschweig and Munich Partner Sites, Munich, Germany
| | - Kaisa Thorell
- Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Daniel Falush
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
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12
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Prada CF, Casadiego MA, Freire CCM. Evolution of Helicobacter spp: variability of virulence factors and their relationship to pathogenicity. PeerJ 2022; 10:e13120. [PMID: 36061745 PMCID: PMC9435515 DOI: 10.7717/peerj.13120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 02/24/2022] [Indexed: 01/12/2023] Open
Abstract
Background Virulence factors (VF) are bacteria-associated molecules that assist to colonize the host at the cellular level. Bacterial virulence is highly dynamic and specific pathogens have a broad array of VFs. The genus Helicobacter is gram-negative, microaerobic, flagellated, and mucus-inhabiting bacteria associated with gastrointestinal inflammation. To investigate about their pathogenicity, several Helicobacter species have been characterized and sequenced. Since the variability and possible origin of VF in the genus are not clear, our goal was to perform a comparative analysis of Helicobacter species in order to investigate VF variability and their evolutionary origin. Methods The complete genomes of 22 Helicobacter species available in NCBI were analyzed, using computational tools. We identifyed gain and loss events in VF genes, which were categorized in seven functional groups to determine their most parsimonious evolutionary origin. After verifying the annotation of all VF genes, a phylogeny from conserved VF organized by Helicobacter species according to gastric Helicobacter species (GHS) or enterohepatic (EHS) classification was obtained. Results Gain and loss analysis of VF orthologous in Helicobacter ssp revealed the most possible evolutionary origin for each gene set. Microevolutionary events in urease and flagella genes were detected during the evolution of the genus. Our results pointed that acquisition of ureases and adherence genes and deletion of cytotoxins in some lineages, as well as variation in VF genes copy number, would be related to host adaptation during evolution of the Helicobacter genus. Our findings provided new insights about the genetic differences between GHS and EHS and their relationship with pathogenicity.
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Affiliation(s)
- Carlos F. Prada
- Department of Genetics and Evolution, Federal University of Sao Carlos, Sao Carlos, Sao Paulo, Brazil,Grupo de Investigación de Biología y Ecología de Artrópodos. Facultad de Ciencias., Universidad del Tolima, Tolima, Colombia
| | - Maria A. Casadiego
- Grupo de Investigación de Biología y Ecología de Artrópodos. Facultad de Ciencias., Universidad del Tolima, Tolima, Colombia
| | - Caio CM Freire
- Department of Genetics and Evolution, Federal University of Sao Carlos, Sao Carlos, Sao Paulo, Brazil
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13
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Hadji M, Mortazavi M, Saberi S, Esmaieli M, Amini N, Akrami R, Daroudian R, Shakeri F, Khedmat H, Pukkala E, Mohammadi M, Zendehdel K. Helicobacter pylori acquisition rates and the associated risk factors amongst newlywed couples; a prospective cohort study in Tehran, Iran. Microbes Infect 2022; 24:104974. [PMID: 35618156 DOI: 10.1016/j.micinf.2022.104974] [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: 12/03/2021] [Revised: 03/19/2022] [Accepted: 03/25/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND The rates and routes of Helicobacter pylori transmission, in a high prevalent country like Iran, with gastric cancer as the leading cause of male cancer mortality is of essence. Here, we have studied the H. pylori-associated risk factors and the likelihood of interspousal transmission. METHODS In a cohort of 686 young prewed couples, questionnaires were self-administered and serum samples were collected, for assessment of risk factors and sero-status of H. pylori, at baseline and follow-up. Of the 475 H. pylori single- or double-seronegative couples, 201 returned for follow-up. The average follow-up duration was 2.2 (SD 0.6) years, with a total of 560.1 person-years. Logistic regression and Cox regression models were used to estimate the odds ratios (ORs) and hazard ratios (HRs). RESULTS The risk of infection was higher in men than women (OR:1.3, 95%CI:1.0-1.8) and among metropolitan than rural residents (OR=1.4, 95%CI:1.1-1.9). The risk of infection was significantly higher among those with three siblings (OR=1.6, 95%CI:1.1-2.2), and four or more siblings (OR=1.4, 95%CI:1.0-1.9), in reference to those with one or no siblings. H. pylori acquisition occurred in 10.9% (27/247) of the H. pylori seronegative participants. The risk of acquisition was significantly higher in older aged (HR=1.2, 95%CI: 1.1-1.3) and higher educated (HR=0.2, 95%CI:0.1-0.9) participants, than younger and illiterate subjects, respectively. Our analysis did not find any evidence for interspousal transmission (HR=1.0, 95%CI: 0.4-2.2). CONCLUSION Although we detected H. pylori acquisition in the young adult Iranian population, our findings did not support interspousal transmission, as a mode of adult H. pylori aquisition.
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Affiliation(s)
- Maryam Hadji
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran; Health Sciences Unit, Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Mahshid Mortazavi
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Saberi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Maryam Esmaieli
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Neda Amini
- Department of Surgery, the Johns Hopkins University School of Medicine, Baltimore, USA
| | - Rahim Akrami
- Department of epidemiology & biostatistics, School of Public health, Sabzevar University of Medical Sciences, Sabzevar, Iran; Department of epidemiology & biostatistics, School of Public health, Tehran University of Medical Sciences, Tehran, Iran
| | - Rana Daroudian
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Shakeri
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Khedmat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Tehran, Iran
| | - Eero Pukkala
- Health Sciences Unit, Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Marjan Mohammadi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| | - Kazem Zendehdel
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran; Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
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14
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Park JM, Lee SY, Kim JH, Sung IK, Park HS. Prognosis of Seronegative Subjects with a Helicobacter pylori-infected Spouse. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background/Aims: Helicobacter pylori (H. pylori) can disseminate between couples. The present study compared the findings of gastric cancer screening between seronegative subjects according to the presence of an infected spouse.Materials and Methods: Follow-up data of seronegative subjects were analyzed among married couples who underwent gastric cancer screening via gastroscopy, serum pepsinogen, and anti-H. pylori IgG assays between January 2010 and May 2016. New detection rates of H. pylori infection and gastric neoplasm at the follow-up screening were compared between seronegative subjects according to the H. pylori-infected status of spouse.Results: Among 246 seronegative subjects with an H. pylori-infected spouse, 92 underwent follow-up tests (case group). Among 278 seronegative subjects with seronegative spouse, 94 underwent follow-up tests (control group). The past infection rate was higher in the case group than in the control group (52/92 vs. 34/94; P=0.005). New H. pylori infection was diagnosed in three of the 92 cases and two of the 94 controls (3.2% vs. 2.1%; P=0.681). During the mean follow-up of 67.9±36.0 months, three adenocarcinomas and two adenomas (5/184) were newly detected among the cases and their spouses, whereas none (0/188) were detected among the controls and their spouses (2.7% vs. 0%; P=0.029).Conclusions: Gastric neoplasm occurred more frequently in couples with an H. pylori-infected spouse. Because the past infection rate is higher among seronegative subjects with an infected spouse, gastric cancer screening is recommended in both partners when the spouse is infected.
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15
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Jiang X, Xu Z, Zhang T, Li Y, Li W, Tan H. Whole-Genome-Based Helicobacter pylori Geographic Surveillance: A Visualized and Expandable Webtool. Front Microbiol 2021; 12:687259. [PMID: 34408729 PMCID: PMC8366602 DOI: 10.3389/fmicb.2021.687259] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/07/2021] [Indexed: 01/08/2023] Open
Abstract
Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.
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Affiliation(s)
- Xiaosen Jiang
- BGI-Shenzhen, Shenzhen, China.,BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Zheng Xu
- BGI-Shenzhen, Shenzhen, China.,Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, China
| | | | - Yuan Li
- BGI-Shenzhen, Shenzhen, China
| | - Wei Li
- BGI-Shenzhen, Shenzhen, China.,BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
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16
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Ailloud F, Estibariz I, Suerbaum S. Evolved to vary: genome and epigenome variation in the human pathogen Helicobacter pylori. FEMS Microbiol Rev 2021; 45:5900976. [PMID: 32880636 DOI: 10.1093/femsre/fuaa042] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is a Gram-negative, spiral shaped bacterium that selectively and chronically infects the gastric mucosa of humans. The clinical course of this infection can range from lifelong asymptomatic infection to severe disease, including peptic ulcers or gastric cancer. The high mutation rate and natural competence typical of this species are responsible for massive inter-strain genetic variation exceeding that observed in all other bacterial human pathogens. The adaptive value of such a plastic genome is thought to derive from a rapid exploration of the fitness landscape resulting in fast adaptation to the changing conditions of the gastric environment. Nevertheless, diversity is also lost through recurrent bottlenecks and H. pylori's lifestyle is thus a perpetual race to maintain an appropriate pool of standing genetic variation able to withstand selection events. Another aspect of H. pylori's diversity is a large and variable repertoire of restriction-modification systems. While not yet completely understood, methylome evolution could generate enough transcriptomic variation to provide another intricate layer of adaptive potential. This review provides an up to date synopsis of this rapidly emerging area of H. pylori research that has been enabled by the ever-increasing throughput of Omics technologies and a multitude of other technological advances.
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Affiliation(s)
- Florent Ailloud
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Iratxe Estibariz
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Sebastian Suerbaum
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany.,DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Pettenkoferstr. 9a, 80336 München, Germany.,National Reference Center for Helicobacter pylori, Pettenkoferstr. 9a, 80336 München, Germany
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17
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Helicobacter Pylori: a comprehensive review for primary care providers. ACTA ACUST UNITED AC 2021; 59:112-118. [PMID: 33565305 DOI: 10.2478/rjim-2020-0043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori is the most prevalent bacteria infecting humans resulting in a variety of gastrointestinal and extra gastrointestinal complications. Although most of the infected adults are asymptomatic, the prevalence varies in different parts of the world it is higher in Eastern and Southern Europe. Eradication of Helicobacter pylori is necessary to prevent precancerous conditions like gastric atrophy, gastric intestinal metaplasia and gastric dysplasia. This comprehensive review addresses briefly on: whom and how to test and treat including recommended first line therapies, salvage therapies, testing for eradication and strategy to be used in primary care clinics.
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18
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Kakiuchi T, Takamori A, Matsuo M. High Prevalence of Helicobacter pylori Infection in Special Needs Schools in Japan. Front Pediatr 2021; 9:697200. [PMID: 34307259 PMCID: PMC8295468 DOI: 10.3389/fped.2021.697200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/03/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Developmental disorders and high Helicobacter pylori (H. pylori) infection rates have been reported. This study aimed to examine the prevalence of H. pylori in a special needs school where all students had developmental disorders in Japan. Methods: In 2017, third-grade junior high school and second- and third-grade high school students attending a special needs school with developmental disorders were enrolled. Participants of Saga Prefecture's H. pylori test and treat project, which comprised third-grade junior high school students not from special needs school, were assigned to the control group. Results: In the control group, H. pylori positive results were 3.18% (228/7,164) students. Similarly, in developmental disorder group, H. pylori positive results were 6.80% (13/191) students. For the developmental disorder and control groups, this present examination sensitivity was 7.03% (13/185), specificity was 96.76% (6,815/7,043), positive predictive value was 5.39% (13/241), negative predictive value was 97.54% (6,815/6,987), Likelihood ratio of a positive result 2.17 and Odds ratio was 2.26 (95% confidence interval: 1.27-4.03, p = 0.005). Conclusion: The prevalence of H. pylori infection was significantly higher in adolescents with developmental disorders than in typically developing adolescents.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Ayako Takamori
- Clinical Research Center, Saga University Hospital, Saga, Japan
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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19
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Koulis A, Busuttil RA, Boussioutas A. Premalignant lesions of the stomach and management of early neoplastic lesions. RESEARCH AND CLINICAL APPLICATIONS OF TARGETING GASTRIC NEOPLASMS 2021:185-216. [DOI: 10.1016/b978-0-323-85563-1.00013-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Molecular Phylogenetic Analysis of 16S rRNA Sequences Identified Two Lineages of Helicobacter pylori Strains Detected from Different Regions in Sudan Suggestive of Differential Evolution. Int J Microbiol 2020; 2020:8825718. [PMID: 33178282 PMCID: PMC7609147 DOI: 10.1155/2020/8825718] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/30/2020] [Accepted: 10/01/2020] [Indexed: 12/22/2022] Open
Abstract
Background Helicobacter pylori (H. pylori) is ubiquitous among humans and one of the best-studied examples of an intimate association between bacteria and humans. Phylogeny and Phylogeography of H. pylori strains are known to mirror human migration patterns and reflect significant demographic events in human prehistory. In this study, we analyzed the molecular evolution of H. pylori strains detected from different tribes and regions of Sudan using 16S rRNA gene and the phylogenetic approach. Materials and methods. A total of 75 gastric biopsies were taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was performed by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the 16S ribosomal gene. Sanger sequencing was applied, and the resulted sequences were matched with the sequences of the National Center for Biotechnology Information (NCBI) nucleotide database. The evolutionary aspects were analyzed using MEGA7 software. Results Molecular detection of H. pylori has shown that 28 (37.33%) of the patients were positive for H. pylori and no significant differences were found in sociodemographic characteristics, endoscopy series, and H. pylori infection. Nucleotide variations were observed at five nucleotide positions (positions 219, 305, 578, 741, and 763-764), and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. These six mutations were detected in regions of the 16S rRNA not closely associated with either tetracycline or tRNA binding sites; 66.67% of them were located in the central domain of 16S rRNA. The phylogenetic analysis of 16S rRNA sequences identified two lineages of H. pylori strains detected from different regions in Sudan. The presence of Sudanese H. pylori strains resembling Hungarian H. pylori strains could reflect the migration of Hungarian people to Sudan or vice versa. Conclusion This finding emphasizes the significance of studying the phylogeny of H. pylori strains as a discriminatory tool to mirror human migration patterns. In addition, the 16S rRNA gene amplification method was found useful for bacterial identification and phylogeny.
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Karcher N, Pasolli E, Asnicar F, Huang KD, Tett A, Manara S, Armanini F, Bain D, Duncan SH, Louis P, Zolfo M, Manghi P, Valles-Colomer M, Raffaetà R, Rota-Stabelli O, Collado MC, Zeller G, Falush D, Maixner F, Walker AW, Huttenhower C, Segata N. Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations. Genome Biol 2020; 21:138. [PMID: 32513234 PMCID: PMC7278147 DOI: 10.1186/s13059-020-02042-y] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 05/11/2020] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out. RESULTS Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300 E. rectale high-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harbor E. rectale. Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure of E. rectale. We confirm that a relatively recently diverged E. rectale subspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis. CONCLUSIONS Our study provides new insights into the population structure and ecology of E. rectale and shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.
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Affiliation(s)
| | - Edoardo Pasolli
- Department of Agriculture, University of Naples, Naples, Italy
| | | | - Kun D Huang
- Department CIBIO, University of Trento, Trento, Italy
- Fondazione Edmund Mach, S. Michele all'Adige, Italy
| | - Adrian Tett
- Department CIBIO, University of Trento, Trento, Italy
| | - Serena Manara
- Department CIBIO, University of Trento, Trento, Italy
| | | | - Debbie Bain
- Rowett Institute, University of Aberdeen, Aberdeen, UK
| | | | - Petra Louis
- Rowett Institute, University of Aberdeen, Aberdeen, UK
| | - Moreno Zolfo
- Department CIBIO, University of Trento, Trento, Italy
| | - Paolo Manghi
- Department CIBIO, University of Trento, Trento, Italy
| | | | | | | | | | | | | | - Frank Maixner
- Institute for Mummy studies, Eurac Research, Bolzano, Italy
| | - Alan W Walker
- Rowett Institute, University of Aberdeen, Aberdeen, UK
| | - Curtis Huttenhower
- Harvard T.H. Chan School of Public Health, Boston, MA, USA
- The Broad Institute, Cambridge, MA, USA
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy.
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Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem. Epidemiol Infect 2019; 147:e276. [PMID: 31552815 PMCID: PMC6807302 DOI: 10.1017/s0950268819001456] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We examined the prevalence and correlates of Helicobacter pylori (H. pylori) infection according to cytotoxin-associated gene A (CagA) phenotype, a main virulence antigen, among the ethnically diverse population groups of Jerusalem. A cross-sectional study was undertaken in Arab (N = 959) and Jewish (N = 692) adults, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori immunoglobulin G (IgG) antibodies. Positive samples were tested for virulence IgG antibodies to recombinant CagA protein, by enzyme-linked immunosorbent assay. Multinomial regression models were fitted to examine associations of sociodemographic factors with H. pylori phenotypes. H. pylori IgG antibody sero-prevalence was 83.3% (95% confidence interval (CI) 80.0%–85.5%) and 61.4% (95% CI 57.7%–65.0%) among Arabs and Jews, respectively. Among H. pylori positives, the respective CagA IgG antibody sero-positivity was 42.3% (95% CI 38.9%–45.8%) and 32.5% (95% CI 28.2%–37.1%). Among Jews, being born in the Former Soviet Union, the Middle East and North Africa, vs. Israel and the Americas, was positively associated with CagA sero-positivity. In both populations, sibship size was positively associated with both CagA positive and negative phenotypes; and education was inversely associated. In conclusion, CagA positive and negative infection had similar correlates, suggesting shared sources of these two H. pylori phenotypes.
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Rahman YA, Ahmed LAW, Hafez RMM, Ahmed RMM. Helicobacter pylori and its hematological effect. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_103_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Inference from the analysis of genetic structure of Helicobacter pylori strains isolates from two paediatric patients with recurrent infection. BMC Microbiol 2019; 19:184. [PMID: 31395006 PMCID: PMC6686460 DOI: 10.1186/s12866-019-1554-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 07/26/2019] [Indexed: 01/06/2023] Open
Abstract
Background Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). Results We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, −B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. Conclusions This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes. Electronic supplementary material The online version of this article (10.1186/s12866-019-1554-z) contains supplementary material, which is available to authorized users.
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Kakiuchi T, Matsuo M, Endo H, Nakayama A, Sato K, Takamori A, Sasaki K, Takasaki M, Hara M, Sakata Y, Okuda M, Kikuchi S, Eguchi Y, Takahashi H, Anzai K, Fujimoto K. A Helicobacter pylori screening and treatment program to eliminate gastric cancer among junior high school students in Saga Prefecture: a preliminary report. J Gastroenterol 2019; 54:699-707. [PMID: 30770975 DOI: 10.1007/s00535-019-01559-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/07/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND To present the strategies and preliminary findings of the first 3 years after implementing a Helicobacter pylori screening and eradication program to prevent gastric cancer in Saga Prefecture. METHODS A screening and treatment program to eradicate H. pylori from third-grade junior high students was started in Saga Prefecture in 2016, using local governmental grants. Screening was with urinary anti-H. pylori antibody tests, followed by H. pylori stool antigen tests for students who were antibody positive. Those positive on both tests underwent H. pylori eradication by triple therapy based on a potassium-competitive acid blocker. RESULTS From 2016 to 2018, the participation rate was 83.1% and the H. pylori infection rate was 3.1% (660/21,042). The participation rates were higher in 2017 (85.4%) and 2018 (85.9%) compared with 2016 (78.5%) (P < 0.0001), and the infection rate also decreased in a time-dependent manner (2016: 3.6%, 2017: 3.3%, 2018: 2.5%, P = 0.0001). In total, 501 students positive for H. pylori received eradication therapy (85.1% success) and adverse events occurred in 20 of these (4.0%). However, no serious complications occurred. CONCLUSIONS The H. pylori screening and eradication project for school students in Saga Prefecture has started successfully and we have seen both a steady increase in the participation rate and a steady decrease in the infection rate, without major safety concerns.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan.
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Hiroyoshi Endo
- Department of Internal Medicine, Saiseikai Karatsu Hospital, 817 Motohata-machi, Karatsu-shi, 847-0852, Japan
| | - Aiko Nakayama
- Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Keiko Sato
- Clinical Research Center, Saga University Hospital, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Ayako Takamori
- Clinical Research Center, Saga University Hospital, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Kazumi Sasaki
- Saga Cancer Center, Saga University Hospital, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Mitsuhiro Takasaki
- Medical Informatics, Saga University Hospital, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Megumi Hara
- Department of Prevention Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Yasuhisa Sakata
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Masumi Okuda
- Department of Pediatrics, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute-shi, 480-1195, Aichi, Japan
| | - Shogo Kikuchi
- Department of Public Health, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute-shi, 480-1195, Aichi, Japan
| | - Yuichiro Eguchi
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Hirokazu Takahashi
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Keizo Anzai
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
| | - Kazuma Fujimoto
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-shi, 849-8501, Saga, Japan
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Smith S, Fowora M, Pellicano R. Infections with Helicobacter pylori and challenges encountered in Africa. World J Gastroenterol 2019; 25:3183-3195. [PMID: 31333310 PMCID: PMC6626727 DOI: 10.3748/wjg.v25.i25.3183] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/02/2019] [Accepted: 06/01/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world’s population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for H. pylori acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high H. pylori prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of H. pylori infection and the low incidence of GC has been reported. This phenomenon is the so-called “African Enigma” and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of H. pylori. The aim of this manuscript is to review current literature on H. pylori infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce H. pylori transmission in this continent.
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Affiliation(s)
- Stella Smith
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Lagos PMB 2013, Nigeria
| | - Muinah Fowora
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Lagos PMB 2013, Nigeria
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Khoder G, Muhammad JS, Mahmoud I, Soliman SSM, Burucoa C. Prevalence of Helicobacter pylori and Its Associated Factors among Healthy Asymptomatic Residents in the United Arab Emirates. Pathogens 2019; 8:E44. [PMID: 30939800 PMCID: PMC6632043 DOI: 10.3390/pathogens8020044] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 03/23/2019] [Accepted: 03/28/2019] [Indexed: 12/24/2022] Open
Abstract
The United Arab Emirates (UAE) has been under continuous populational influences from Asia, Europe, and Africa, making it an ideal site for epidemiological studies on Helicobacter pylori. However, there has been a paucity of well-designed prevalence studies on H. pylori from UAE. The aim of this study was to determine the prevalence of H. pylori and its associated risk factors in the UAE. A prospective cross-sectional study was conducted on healthy asymptomatic residents of UAE. Socio-demographic, lifestyle, and gastrointestinal characteristics of participants were obtained through a questionnaire in parallel within the stool sample collection. A total of 350 participants were included in this study and were tested for H. pylori using the stool antigen test (Premier Platinum HpSAT). Out of the total tested study participants, 41% were found to be H. pylori-infected. Logistic regression analysis has shown a significant association between H. pylori infection and gender, age, ethnicity, profession, domestic overcrowding, source of drinking water, and gastrointestinal characteristics of participants. Based on the results from this study, we suggest that preventive measures against H. pylori infection should be considered worthy by public health authorities.
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Affiliation(s)
- Ghalia Khoder
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, UAE.
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE.
| | - Jibran Sualeh Muhammad
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE.
| | - Ibrahim Mahmoud
- Department of Family Medicine and Behavioral Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE.
| | - Sameh S M Soliman
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, UAE.
| | - Christophe Burucoa
- Laboratoire de bactériologie, Hygiène, EA 4331 LITEC, CHU de Poitiers, Université de Poitiers, Poitiers 86000, France.
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Help, hope and hype: ethical considerations of human microbiome research and applications. Protein Cell 2019; 9:404-415. [PMID: 29675808 PMCID: PMC5960465 DOI: 10.1007/s13238-018-0537-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Kayali S, Manfredi M, Gaiani F, Bianchi L, Bizzarri B, Leandro G, Di Mario F, De' Angelis GL. Helicobacter pylori, transmission routes and recurrence of infection: state of the art. ACTA BIO-MEDICA : ATENEI PARMENSIS 2018; 89:72-76. [PMID: 30561421 PMCID: PMC6502203 DOI: 10.23750/abm.v89i8-s.7947] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is one of the most common infection in humans, affecting more than half of the population. The prevalence of the infection varies widely in rural developing areas (more than 80%) compared to urban developed ones (less than 40%), as a consequence of different socioeconomic and hygienic conditions. H. pylori infection is usually acquired during childhood; infected people usually remain asymptomatic, but about 30% of individuals may develop mild to severe upper gastrointestinal diseases such as gastritis, peptic ulcer, gastric cancer or MALT lymphoma. The transmission route is not clear yet; the person-to-person transmission, especially within the same family appears to be prevalent, but also environmental contamination is possible. The eradication without a specific therapeutic regimen is very unlikely and the reinfection rate after an effective eradication therapy is quite rare. The reinfection rate will increase if there are family members affected.
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Affiliation(s)
- Stefano Kayali
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
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Tavera G, Morgan DR, Williams SM. Tipping the Scale Toward Gastric Disease: A Host-Pathogen Genomic Mismatch? CURRENT GENETIC MEDICINE REPORTS 2018; 6:199-207. [PMID: 30775159 PMCID: PMC6373874 DOI: 10.1007/s40142-018-0153-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Chronic infection with Helicobacter pylori infection is necessary but not sufficient to initiate development of intestinal-type gastric adenocarcinoma. It is not clear what additional factors tip the scale from commensal bacteria towards a pathogen that facilitates development of gastric cancer. Genetic variants in both the pathogen and host have been implicated, but neither alone explains a substantial portion of disease risk. RECENT FINDINGS In this review, we consider studies that address the important role of human and bacterial genetics, ancestry and their interactions in determining gastric disease risk. We observe gaps in the current literature that should guide future work to confirm the hypothesis of the interacting roles of host and bacterial genetics that will be necessary to translate these findings into clinically relevant information. SUMMARY We summarize genetic risk factors for gastric disease in both H. pylori and human hosts. However, genetic variation of one or the other organism in isolation insufficiently explains gastric disease risk. The most promising models of gastric disease risk simultaneously consider the genetic variation of both the H. pylori and human host, under a co-evolution model.
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Affiliation(s)
- Gloria Tavera
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Douglas R Morgan
- Vanderbilt Ingram Cancer Center, Nashville, Tennessee
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Scott M Williams
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
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Chattopadhyay S, Chi PB, Minin VN, Berg DE, Sokurenko EV. Recombination-independent rapid convergent evolution of the gastric pathogen Helicobacter pylori. BMC Genomics 2018; 19:835. [PMID: 30463511 PMCID: PMC6249973 DOI: 10.1186/s12864-018-5231-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 11/07/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Helicobacter pylori is a human stomach pathogen, naturally-competent for DNA uptake, and prone to homologous recombination. Extensive homoplasy (i.e., phylogenetically-unlinked identical variations) observed in H. pylori genes is considered a hallmark of such recombination. However, H. pylori also exhibits a high mutation rate. The relative adaptive role of homologous recombination and mutation in species diversity is a highly-debated issue in biology. Recombination results in homoplasy. While convergent mutation can also account for homoplasy, its contribution is thought to be minor. We demonstrate here that, contrary to dogma, convergent mutation is a key contributor to Helicobacter pylori homoplasy, potentially driven by adaptive evolution of proteins. RESULTS Our present genome-wide analysis shows that homoplastic nonsynonymous (amino acid replacement) changes are not typically accompanied by homoplastic synonymous (silent) variations. Moreover, the majority of the codon positions with homoplastic nonsynonymous changes also contain different (i.e. non-homoplastic) nonsynonymous changes arising from mutation only. This indicates that, to a considerable extent, nonsynonymous homoplasy is due to convergent mutations. High mutation rate or limited availability of evolvable sites cannot explain this excessive convergence, as suggested by our simulation studies. Rather, the genes with convergent mutations are overrepresented in distinct functional categories, suggesting possible selective responses to conditions such as distinct micro-niches in single hosts, and to differences in host genotype, physiology, habitat and diet. CONCLUSIONS We propose that mutational convergence is a key player in H. pylori's adaptation and extraordinary persistence in human hosts. High frequency of mutational convergence could be due to saturation of evolvable sites capable of responding to selection pressures, while the number of mutable residues is far from saturation. We anticipate a similar scenario of mutational vs. recombinational genome dynamics or plasticity for other naturally competent microbes where strong positive selection could favor frequent convergent mutations in adaptive protein evolution.
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Affiliation(s)
| | - Peter B Chi
- Department of Mathematics and Statistics, Villanova University, Villanova, PA, USA
| | - Vladimir N Minin
- Department of Statistics, University of California, Irvine, California, USA
| | - Douglas E Berg
- Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Evgeni V Sokurenko
- Department of Microbiology, University of Washington, Seattle, Washington, USA
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Helicobacter pylori Infection and Its Risk Factors: A Prospective Cross-Sectional Study in Resource-Limited Settings of Northwest Ethiopia. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2018; 2018:9463710. [PMID: 30420905 PMCID: PMC6211158 DOI: 10.1155/2018/9463710] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 09/19/2018] [Indexed: 12/13/2022]
Abstract
Background Helicobacter pylori (H. pylori) is implicated for the causation of gastrointestinal tract infections including gastric cancer. Although the infection is prevalent globally, the impact is immense in countries with poor environmental and socioeconomic status including Ethiopia. Epidemiological study on the magnitude of H. pylori and possible risk factors has priceless implication. Therefore, in this study, we determined the prevalence and risk factors of H. pylori infection in the resource-limited area of northwest Ethiopia. Methods A prospective cross-sectional study was conducted on northwest Ethiopia among 201 systematically selected dyspeptic patients. Data were collected using a structured and pretested questionnaire, and stool and serum samples were collected and analyzed by SD BIOLINE H. pylori Ag and dBest H. pylori Disk tests, respectively. Chi-square test was performed to see association between variables, and binary and multinomial regression tests were performed to identify potential risk factors. P values <0.05 were taken statistically significant. Result Prevalence of H. pylori was found to be 71.1% (143/201) and 37.3% (75/201) using the dBest H. pylori Test Disk and SD BIOLINE H. pylori Ag test, respectively. H. pylori seropositivity, using dBest H. pylori Disk tests, is significantly associated in age groups <10 years (P=0.044) and married patients (P=0.016). In those patients with H. pylori (a positive result with either the Ab or Ag test), drinking water from well sources had 2.23 times risk of getting H. pylori infection (P=0.017), and drinking coffee (1.51 (0.79–2.96, P=0.025)) and chat chewing (1.78 (1.02–3.46, P=0.008) are the common risk factors. Conclusion The present study discovered considerable magnitude of H. pylori among the dyspeptic patients in the study area. H. pylori infection is frequent in individuals drinking water from well sources, and thus, poor sanitation and unhygienic water supply are contributing factors. Policies aiming at improving the socioeconomic status will reduce potential sources of infection, transmission, and ultimately the prevalence and incidence of H. pylori.
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Smet A, Yahara K, Rossi M, Tay A, Backert S, Armin E, Fox JG, Flahou B, Ducatelle R, Haesebrouck F, Corander J. Macroevolution of gastric Helicobacter species unveils interspecies admixture and time of divergence. THE ISME JOURNAL 2018; 12:2518-2531. [PMID: 29942073 PMCID: PMC6154992 DOI: 10.1038/s41396-018-0199-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/29/2018] [Accepted: 03/20/2018] [Indexed: 12/17/2022]
Abstract
Since the discovery of the human pathogen Helicobacter pylori, various other Helicobacter species have been identified in the stomach of domesticated and wild mammals. To better understand the evolutionary history of these ecologically similar but genetically distinct species, we analyzed 108 gastric Helicobacter genomes and included 54 enterohepatic Helicobacter genomes for comparison purposes. An admixture analysis supported the presence of an ecological barrier, preventing the genetic exchange between the gastric and enterohepatic Helicobacter species, and unraveled many gene flow events within and across species residing in the stomach. As pets can be colonized by multiple gastric Helicobacter species, the genetic exchange between the canine and feline strains was evident, with H. heilmannii and H. bizzozeronii showing the highest interspecies recombination. An admixture between H. pylori (in particular, the ancestral African strains), H. acinonychis from wild felines and H. cetorum from marine mammals was also identified. Because these latter species do not share the same host, this phenomenon is most likely a remaining signal of shared ancestry. A reconstruction of the time of divergence of the gastric Helicobacter spp. revealed that the domestic animal-related Helicobacter species evolved in parallel with H. pylori and its two closest relatives (H. acinonychis and H. cetorum), rather than together.
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Affiliation(s)
- Annemieke Smet
- Laboratory Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
| | - Koji Yahara
- Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
| | - Mirko Rossi
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
| | - Alfred Tay
- The Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Perth, WA, Australia
| | - Steffen Backert
- Department Biology, Division Microbiology, University Erlangen Nuremberg, Erlangen, Germany
| | - Ensser Armin
- Institute of clinical and Molecular Virology, Universitätsklinikum Erlangen, Erlangen, Germany
| | - James G Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Bram Flahou
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Richard Ducatelle
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Freddy Haesebrouck
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jukka Corander
- Department of Biostatistics, University of Oslo, Oslo, Norway
- Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
- Welcome Trust Sanger Institute, Cambridge, UK
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Sgambato D, Visciola G, Ferrante E, Miranda A, Romano L, Tuccillo C, Manguso F, Romano M. Prevalence of Helicobacter pylori infection in sexual partners of H. pylori-infected subjects: Role of gastroesophageal reflux. United European Gastroenterol J 2018; 6:1470-1476. [PMID: 30574317 PMCID: PMC6297926 DOI: 10.1177/2050640618800628] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/13/2018] [Indexed: 12/21/2022] Open
Abstract
Background Helicobacter pylori is transmitted through faecal-oral or oral-oral routes. Whether H. pylori infection is more prevalent in sexual partners of H. pylori-infected subjects is unclear. Objective We evaluated 1) the prevalence of H. pylori infection in sexual partners of H. pylori-infected subjects; and 2) whether presence of gastroesophageal reflux in H. pylori-infected subjects was associated with transmission of infection to their sexual partners. Methods We evaluated H. pylori infection by 13C Urea Breath Test in sexual partners of 161 consecutive patients with H. pylori-related dyspepsia. The case-control group consisted of 161 dyspeptic subjects undergoing the 13C Urea Breath Test. The prevalence of reflux symptoms was noted through the Leeds scale. The role of gastroesophageal reflux in transmission of H. pylori infection was evaluated by binary logistic regression. A two-tailed p value of 0.05 or less was considered significant. Results Prevalence of H. pylori infection in sexual partners of H. pylori-infected subjects is 74.5% whereas prevalence of H. pylori infection in the control group is 32.3%, p<0.05. At the logistic regression analysis, the presence of reflux symptoms in H. pylori-infected subjects is independently associated with concomitant infection in both members of the couple (odds ratio 4.41, 95% confidence interval 1.6-12.3) and with length of cohabitation (odds ratio 2.39, 95% confidence interval 1.0-5.7). Conclusions The prevalence of H. pylori infection is significantly higher in sexual partners of H. pylori-infected subjects than in controls. Members of a couple are four times more likely to be both H. pylori infected if one of the couple has reflux symptoms.
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Affiliation(s)
- Dolores Sgambato
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | - Giulio Visciola
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | - Emanuele Ferrante
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | - Agnese Miranda
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | - Lorenzo Romano
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | - Concetta Tuccillo
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
| | | | - Marco Romano
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania "Luigi Vanvitelli" and University Hospital
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Bravo D, Hoare A, Soto C, Valenzuela MA, Quest AFG. Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World J Gastroenterol 2018; 24:3071-3089. [PMID: 30065554 PMCID: PMC6064966 DOI: 10.3748/wjg.v24.i28.3071] [Citation(s) in RCA: 138] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/17/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
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Affiliation(s)
- Denisse Bravo
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Anilei Hoare
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Cristopher Soto
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Manuel A Valenzuela
- Advanced Center for Chronic Diseases, Institute for Health-Related Research and Innovation, Faculty of Health Sciences, Universidad Central de Chile, Santiago 8380447, Chile
| | - Andrew FG Quest
- Advanced Center for Chronic Diseases, Center for Studies on Exercise, Metabolism and Cancer, Biomedical Science Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380447, Chile
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Talebi Bezmin Abadi A. Diagnosis of Helicobacter pylori Using Invasive and Noninvasive Approaches. J Pathog 2018; 2018:9064952. [PMID: 29951318 PMCID: PMC5987299 DOI: 10.1155/2018/9064952] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/12/2018] [Indexed: 01/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) as gram-negative and spiral microorganism is responsible for colonization in the gastric microniche for more than 50% of world population. Recent studies have shown a critical role of H. pylori in the development of peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. Over the past decade, there has been a sharp interest to use noninvasive tests in diagnosis of the H. pylori infection. During the years after discovery by Marshall and Warren, it has been frequently declared that the rapid urease test (RUT) is one of the cheapest and rapid diagnostic approaches used in detecting the infection. Although the specificity and sensitivity are durable for this test, clinical experiences had shown that the ideal results are only achieved only if we take biopsies from both corpus and antrum at the same time. Given the diagnosis of the H. pylori in clinical samples, gastroenterologists are facing a long list of various molecular and nonmolecular tests. We need more in-depth researches and investigations to correctly generalize rapid and accurate molecular tests determining both bacterial identity and antibiotic resistance profile.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Sprockett D, Fukami T, Relman DA. Role of priority effects in the early-life assembly of the gut microbiota. Nat Rev Gastroenterol Hepatol 2018; 15:197-205. [PMID: 29362469 PMCID: PMC6813786 DOI: 10.1038/nrgastro.2017.173] [Citation(s) in RCA: 238] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Understanding how microbial communities develop is essential for predicting and directing their future states. Ecological theory suggests that community development is often influenced by priority effects, in which the order and timing of species arrival determine how species affect one another. Priority effects can have long-lasting consequences, particularly if species arrival history varies during the early stage of community development, but their importance to the human gut microbiota and host health remains largely unknown. Here, we explore how priority effects might influence microbial communities in the gastrointestinal tract during early childhood and how the strength of priority effects can be estimated from the composition of the microbial species pool. We also discuss factors that alter microbial transmission, such as delivery mode, diet and parenting behaviours such as breastfeeding, which can influence the likelihood of priority effects. An improved knowledge of priority effects has the potential to inform microorganism-based therapies, such as prebiotics and probiotics, which are aimed at guiding the microbiota towards a healthy state.
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Affiliation(s)
- Daniel Sprockett
- Department of Microbiology and Immunology, Stanford University School ofMedicine, 291 Campus Drive, Stanford, California 94305, USA
| | - Tadashi Fukami
- Department of Biology, Stanford University, 371 Serra Mall, Stanford, California 94305, USA
| | - David A Relman
- Department of Microbiology and Immunology, Stanford University School ofMedicine, 291 Campus Drive, Stanford, California 94305, USA
- Department of Medicine, Stanford University School of Medicine, 291 Campus Drive, Stanford, California 94305, USA
- Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USA
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Kienesberger S, Perez-Perez GI, Olivares AZ, Bardhan P, Sarker SA, Hasan KZ, Sack RB, Blaser MJ. When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children. Gut Microbes 2018; 9:252-263. [PMID: 29494270 PMCID: PMC6219588 DOI: 10.1080/19490976.2017.1421887] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.
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Affiliation(s)
- Sabine Kienesberger
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, USA,Institute of Molecular Biosciences, University of Graz, Graz, Styria, Austria,BioTechMed-Graz, Graz, Styria, Austria
| | - Guillermo I. Perez-Perez
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, USA,CONTACT Guillermo I. Perez-Perez Department of Medicine, University Langone Medical Center, 6027W 423 East 23th street, NY 10010, New York, USA
| | - Asalia Z. Olivares
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, USA
| | - Pradip Bardhan
- Nutrition and Clinical Services Division, ICDDR, Dhaka, Bangladesh
| | | | - Kh. Zahid Hasan
- Nutrition and Clinical Services Division, ICDDR, Dhaka, Bangladesh
| | - R. Bradley Sack
- Department of International Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Martin J. Blaser
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, USA,Veterans Administration Medical Center, New York, USA
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Delahay RM, Croxall NJ, Stephens AD. Phylogeographic diversity and mosaicism of the Helicobacter pylori tfs integrative and conjugative elements. Mob DNA 2018; 9:5. [PMID: 29416569 PMCID: PMC5785829 DOI: 10.1186/s13100-018-0109-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 01/15/2018] [Indexed: 12/12/2022] Open
Abstract
Background The genome of the gastric pathogen Helicobacter pylori is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the cag pathogenicity island (cagPAI) and two mobile integrative and conjugative elements (ICEs) termed tfs3 and tfs4. All three islands are implicated as virulence factors, although whereas the cagPAI is well characterised, understanding of how the tfs elements influence H. pylori interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global H. pylori population. Results To gain a global perspective of tfs ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full tfs pan-gene content contained within a global collection of 221 draft and complete H. pylori genome sequences. Complete (ca. 35-55kbp) and remnant tfs ICE clusters were reconstructed from a dataset comprising > 12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different tfs ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of tfs ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular H. pylori phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement. Conclusions Our collective results establish a clear view of tfs ICE diversity and phylogeographic representation in the global H. pylori population, and provide a robust contextual framework for elucidating the functional role of the tfs ICEs particularly as it relates to the risk of gastric disease associated with different tfs ICE genotypes. Electronic supplementary material The online version of this article (10.1186/s13100-018-0109-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Robin M Delahay
- 1Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Nicola J Croxall
- 1Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Amberley D Stephens
- 1Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.,2Present Address: Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcette Drive, West Cambridge, Cambridge, CB3 0AS UK
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Amaral O, Fernandes I, Veiga N, Pereira C, Chaves C, Nelas P, Silva D. Living Conditions and Helicobacter pylori in Adults. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9082716. [PMID: 29159181 PMCID: PMC5660766 DOI: 10.1155/2017/9082716] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 09/03/2017] [Accepted: 09/12/2017] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Infection by the bacterium Helicobacter pylori (H. pylori) is transmissible and is considered a public health issue which affects people of all ages. The objective of this study was to identify factors (lifestyles, dietary factors, and hygiene conditions) related to the prevalence of H. pylori infection. METHODS We carried out an observational cross-sectional study with a community sample of adults from the municipalities of Viseu and Sátão, Portugal. The final sample resulted in 166 adults. The data were collected through a self-administered questionnaire with questions regarding sociodemographic aspects and lifestyles. H. pylori infection was identified using the 13C-urea breath test. RESULTS No association was found between the prevalence of H. pylori infection and the use of tobacco, alcohol, or coffee or dietary factors. The prevalence of H. pylori infection was higher in adults who reported higher consumption of fried food and lower consumption of vegetables and fruit. H. pylori infection was significant for the variables of lower frequency of handwashing before going to the bathroom (p = 0.02) and well water consumption (p = 0.05). CONCLUSION A significant association was found for H. pylori infection with the lower frequency of handwashing before going to the bathroom and the consumption of well water.
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Affiliation(s)
- Odete Amaral
- CI&DETS, Polytechnic Institute of Viseu, Viseu, Portugal
| | | | - Nélio Veiga
- Health Sciences Institute, Universidade Católica Portuguesa, Lisbon, Portugal
- Centre for Interdisciplinary Research in Health (CIIS), Universidade Católica Portuguesa, Lisbon, Portugal
| | - Carlos Pereira
- CI&DETS, Polytechnic Institute of Viseu, Viseu, Portugal
| | - Claudia Chaves
- CI&DETS, Polytechnic Institute of Viseu, Viseu, Portugal
| | - Paula Nelas
- CI&DETS, Polytechnic Institute of Viseu, Viseu, Portugal
| | - Daniel Silva
- CI&DETS, Polytechnic Institute of Viseu, Viseu, Portugal
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Sandoval-Motta S, Aldana M, Martínez-Romero E, Frank A. The Human Microbiome and the Missing Heritability Problem. Front Genet 2017; 8:80. [PMID: 28659968 PMCID: PMC5468393 DOI: 10.3389/fgene.2017.00080] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 05/29/2017] [Indexed: 12/13/2022] Open
Abstract
The "missing heritability" problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this "missing heritability" have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies.
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Affiliation(s)
- Santiago Sandoval-Motta
- Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
| | - Maximino Aldana
- Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de MéxicoMexico City, Mexico.,Instituto de Ciencias Físicas, Universidad Nacional Autónoma de MéxicoMorelos, Mexico
| | | | - Alejandro Frank
- Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de MéxicoMexico City, Mexico.,Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de MéxicoMexico City, Mexico.,Member of El Colegio NacionalMexico City, Mexico
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Thorell K, Yahara K, Berthenet E, Lawson DJ, Mikhail J, Kato I, Mendez A, Rizzato C, Bravo MM, Suzuki R, Yamaoka Y, Torres J, Sheppard SK, Falush D. Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas. PLoS Genet 2017; 13:e1006546. [PMID: 28231283 PMCID: PMC5322909 DOI: 10.1371/journal.pgen.1006546] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 12/19/2016] [Indexed: 12/13/2022] Open
Abstract
For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations. Helicobacter pylori is one of the best studied examples of an intimate association between bacteria and humans, due to its ability to colonize the stomach for decades and to transmit from generation to generation. A number of studies have sought to link diversity in H. pylori to human migrations but there are some discordant signals such as an “out of Africa” dispersal within the last few thousand years that has left a much stronger signal in bacterial genomes than in human ones. In order to understand how such discrepancies arise, we have investigated the evolution of H. pylori during the recent colonization of the Americas. We find that bacterial populations evolve quickly and can spread rapidly to people of different ethnicities. Distinct new bacterial subpopulations have formed in Colombia from a European source and in Nicaragua and the US from African sources. Genetic exchange between bacterial populations is rampant within Central and South America but is uncommon within North America, which may reflect differences in prevalence. Our results also suggest that adaptation of bacteria to particular human ethnic groups may be confined to a handful of genes involved in interaction with the immune system.
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Affiliation(s)
- Kaisa Thorell
- Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Koji Yahara
- Dept. of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Elvire Berthenet
- Medical Microbiology and Infectious Disease group, Swansea University, Swansea, Wales, United Kingdom
| | - Daniel J. Lawson
- Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Jane Mikhail
- Medical Microbiology and Infectious Disease group, Swansea University, Swansea, Wales, United Kingdom
| | - Ikuko Kato
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America
| | - Alfonso Mendez
- Instituto Politecnico Nacional, ENCB, Mexico City, Mexico
| | - Cosmeri Rizzato
- Dipartimento di Ricerca Traslazionale e Nuove Tecnologie in Medicina e Chirurgia, Universitá di Pisa, Pisa, Italy
| | - María Mercedes Bravo
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogota, Colombia
| | - Rumiko Suzuki
- Dept. of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan
| | - Yoshio Yamaoka
- Dept. of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan
| | - Javier Torres
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatria, IMSS, Mexico City, Mexico
| | - Samuel K. Sheppard
- Milner Center for Evolution, Dept. of Biology and Biochemistry, University of Bath, Bath, United Kingdom
| | - Daniel Falush
- Milner Center for Evolution, Dept. of Biology and Biochemistry, University of Bath, Bath, United Kingdom
- * E-mail:
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Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212-239. [PMID: 28071659 DOI: 10.1038/ajg.2016.563] [Citation(s) in RCA: 985] [Impact Index Per Article: 123.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 10/07/2016] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.
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Affiliation(s)
- William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA
| | | | - Colin W Howden
- Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Steven F Moss
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
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44
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Chuong KH, Hwang DM, Tullis DE, Waters VJ, Yau YCW, Guttman DS, O'Doherty KC. Navigating social and ethical challenges of biobanking for human microbiome research. BMC Med Ethics 2017; 18:1. [PMID: 28077127 PMCID: PMC5225618 DOI: 10.1186/s12910-016-0160-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 12/16/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Biobanks are considered to be key infrastructures for research development and have generated a lot of debate about their ethical, legal and social implications (ELSI). While the focus has been on human genomic research, rapid advances in human microbiome research further complicate the debate. DISCUSSION We draw on two cystic fibrosis biobanks in Toronto, Canada, to illustrate our points. The biobanks have been established to facilitate sample and data sharing for research into the link between disease progression and microbial dynamics in the lungs of pediatric and adult patients. We begin by providing an overview of some of the ELSI associated with human microbiome research, particularly on the implications for the broader society. We then discuss ethical considerations regarding the identifiability of samples biobanked for human microbiome research, and examine the issue of return of results and incidental findings. We argue that, for the purposes of research ethics oversight, human microbiome research samples should be treated with the same privacy considerations as human tissues samples. We also suggest that returning individual microbiome-related findings could provide a powerful clinical tool for care management, but highlight the need for a more grounded understanding of contextual factors that may be unique to human microbiome research. CONCLUSIONS We revisit the ELSI of biobanking and consider the impact that human microbiome research might have. Our discussion focuses on identifiability of human microbiome research samples, and return of research results and incidental findings for clinical management.
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Affiliation(s)
- Kim H Chuong
- Department of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - David M Hwang
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada.,University Health Network, Toronto, Canada
| | - D Elizabeth Tullis
- Adult Cystic Fibrosis, University of Toronto, Toronto, Canada.,Toronto Adult Cystic Fibrosis Centre, St Michael's Hospital, Toronto, Canada
| | - Valerie J Waters
- Department of Paediatrics, University of Toronto, Toronto, Canada.,Division of Infectious Diseases, Hospital for Sick Children, Toronto, Canada
| | - Yvonne C W Yau
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada.,Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada
| | - David S Guttman
- Department of Cell & Systems Biology, Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, Canada
| | - Kieran C O'Doherty
- Department of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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Lewinska A, Wnuk M. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases. Biogerontology 2017; 18:293-299. [PMID: 28074309 PMCID: PMC5350214 DOI: 10.1007/s10522-017-9676-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 01/02/2017] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.
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Affiliation(s)
- Anna Lewinska
- Department of Genetics, University of Rzeszow, Werynia 502, 36-100, Kolbuszowa, Poland.
| | - Maciej Wnuk
- Department of Genetics, University of Rzeszow, Werynia 502, 36-100, Kolbuszowa, Poland.
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Mamishi S, Eshaghi H, Mahmoudi S, Bahador A, Hosseinpour Sadeghi R, Najafi M, Farahmand F, Khodadad A, Pourakbari B. Intrafamilial transmission of Helicobacter pylori: genotyping of faecal samples. Br J Biomed Sci 2016; 73:38-43. [PMID: 27182676 DOI: 10.1080/09674845.2016.1150666] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND After more than 20 years of research, there is a little information about the detailed routes of Helicobacter pylori transmission. The aim of this study was to explore intrafamilial transmission of H. pylori in children who had indication for upper gastrointestinal endoscopy and their parents. METHODS Children (aged up to 15 years) were studied during September 2012 to October 2013. The parents of those with positive urea breath test results were asked to provide faecal and blood samples after giving informed consent. Non-invasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in faeces were measured. The genetic similarity of the family strains was investigated by the random amplification of polymorphic DNA (RAPD-PCR) genotyping method. RESULTS According to the genotyping results of 30 families, in 10 (33.3%) children related H. pylori genotypes to their mothers were found, while only 2 children (6.7%) had similar genotypes to their fathers. Interestingly, children with similar H. pylori genotype with their mothers had higher IgA (35.7 ± 10.8) and IgM antibody titres (87.23 ± 19.15) than other children. In addition, in these children, lower titres of IgG antibodies (9.93 ± 3.31) were found rather than children who had no H. pylori in their faeces or had no similarities with their parents (30.28 ± 6.15). CONCLUSIONS In conclusion, mother-to-child transmission is the main route of intrafamilial transmission of H. pylori in Iranian families. Molecular typing of H. pylori can be useful in identifying a high-risk population.
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Affiliation(s)
- Setareh Mamishi
- a Department of Pediatric Infectious Disease, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,b Pediatric Infectious Diseases Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Hamid Eshaghi
- a Department of Pediatric Infectious Disease, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Shima Mahmoudi
- b Pediatric Infectious Diseases Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Abbas Bahador
- c Department of Microbiology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | | | - Mehri Najafi
- d Department of Pediatric Gastroenterology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Fatemeh Farahmand
- d Department of Pediatric Gastroenterology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Ahmad Khodadad
- d Department of Pediatric Gastroenterology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Babak Pourakbari
- b Pediatric Infectious Diseases Research Center , Tehran University of Medical Sciences , Tehran , Iran
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47
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Helicobacter pylori outer membrane protein and virulence marker differences in expatriate patients. Epidemiol Infect 2016; 144:2200-8. [PMID: 26941114 DOI: 10.1017/s095026881600025x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We studied the prevalence of Helicobacter pylori virulence markers, e.g. cytotoxin associated gene (cagA), cagA promoter, vacuolating associated cytotoxin A (vacA) alleles induced by contact with epithelium (iceA type), and outer membrane protein Q (hopQ) in expatriates and compared them with those in local residents. Gastric biopsies were obtained at endoscopy for culture, histology and PCR for virulence marker and hopQ. Of 309 patients, 236 (76%) were males with a mean age of 45 years. A total of 102 patients were expatriates. hopQ type 1 was present in 98 (47%) local residents compared to 88 (86%) expatriates (P < 0·001), while hopQ type 2 was present in 176 (85%) local residents, compared to 60 (59%) expatriates (P < 0·001). H. pylori virulence marker cagA was positive in 97 (47%) local residents compared to 86 (84%) expatriates (P < 0·001) while cagA-P was positive in 72 (35%) local residents compared to 87 (85%) expatriates (P < 0·001). iceA type 1 was positive in 157 (76%) local residents compared to 45 (44%) expatriates (P < 0·001), while iceA type 2 was positive in 81 (39%) local residents compared to 86 (84%) expatriates (P < 0·001). Distribution of H. pylori cagA, cagA promoter, iceA and hopQ type in local residents and expatriates was different. H. pylori virulence markers were associated with severe pathology in expatriates.
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48
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Maixner F, Krause-Kyora B, Turaev D, Herbig A, Hoopmann MR, Hallows JL, Kusebauch U, Vigl EE, Malfertheiner P, Megraud F, O'Sullivan N, Cipollini G, Coia V, Samadelli M, Engstrand L, Linz B, Moritz RL, Grimm R, Krause J, Nebel A, Moodley Y, Rattei T, Zink A. The 5300-year-old Helicobacter pylori genome of the Iceman. Science 2016; 351:162-165. [PMID: 26744403 DOI: 10.1126/science.aad2545] [Citation(s) in RCA: 129] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H. pylori is known to be a hybrid between Asian and African bacteria, but there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans. Here, we present a 5300-year-old H. pylori genome from a European Copper Age glacier mummy. The "Iceman" H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years.
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Affiliation(s)
- Frank Maixner
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
| | - Ben Krause-Kyora
- Institute of Clinical Molecular Biology, Kiel University, Schittenhelmstr. 12, 24105 Kiel, Germany
| | - Dmitrij Turaev
- CUBE - Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Althanstr. 14, 1090 Vienna, Austria
| | - Alexander Herbig
- Institute for Archaeological Sciences, University of Tübingen, Rümelinstr. 23, 72072 Tübingen, Germany.,Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany
| | - Michael R Hoopmann
- Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA
| | - Janice L Hallows
- Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA
| | - Ulrike Kusebauch
- Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA
| | - Eduard Egarter Vigl
- Scuola Superiore Sanitaria Provinciale "Claudiana", Via Lorenz Böhler 13, 39100 Bolzano, Italy
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany
| | - Francis Megraud
- Université de Bordeaux, Centre National de Référence des Helicobacters et Campylobacters and INSERM U853, 146 rue Léo Saignat, 33076 Bordeaux, France
| | - Niall O'Sullivan
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
| | - Giovanna Cipollini
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
| | - Valentina Coia
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
| | - Marco Samadelli
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
| | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 141 83 Stockholm, Sweden
| | - Bodo Linz
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA
| | - Robert L Moritz
- Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA
| | - Rudolf Grimm
- Robert Mondavi Institute for Food Science, University of California, Davis, California 95616, USA
| | - Johannes Krause
- Institute for Archaeological Sciences, University of Tübingen, Rümelinstr. 23, 72072 Tübingen, Germany.,Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany
| | - Almut Nebel
- Institute of Clinical Molecular Biology, Kiel University, Schittenhelmstr. 12, 24105 Kiel, Germany
| | - Yoshan Moodley
- Department of Zoology, University of Venda, Private Bag X5050, Thohoyandou 0950, Republic of South Africa.,Department of Integrative Biology and Evolution, Konrad Lorenz Institute for Ethology, University of Veterinary Medicine Vienna, Savoyenstr. 1a, 1160 Vienna, Austria
| | - Thomas Rattei
- CUBE - Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Althanstr. 14, 1090 Vienna, Austria
| | - Albert Zink
- Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy
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49
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O'Doherty KC, Virani A, Wilcox ES. The Human Microbiome and Public Health: Social and Ethical Considerations. Am J Public Health 2016; 106:414-20. [PMID: 26794165 DOI: 10.2105/ajph.2015.302989] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Rapid advances in human microbiome research point to an increasing range of health outcomes related to the composition of an individual's microbiome. To date, much research has focused on individual health, with a paucity of attention to public health implications. This is a critical oversight owing to the potentially shared nature of the human microbiome across communities and vertical and horizontal mechanisms for transferring microbiomes among humans. We explored some key ethical and social implications of human microbiome research for public health. We focused on (1) insights from microbiome research about damage to individual and shared microbiomes from prevalent societal practices, and (2) ethical and social implications of novel technologies developed on the basis of emerging microbiome science.
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Affiliation(s)
- Kieran C O'Doherty
- Kieran C. O'Doherty is with the Department of Psychology, University of Guelph, Guelph, ON, Canada. Alice Virani is with the Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Elizabeth S. Wilcox is with the School of Population and Public Health, University of British Columbia
| | - Alice Virani
- Kieran C. O'Doherty is with the Department of Psychology, University of Guelph, Guelph, ON, Canada. Alice Virani is with the Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Elizabeth S. Wilcox is with the School of Population and Public Health, University of British Columbia
| | - Elizabeth S Wilcox
- Kieran C. O'Doherty is with the Department of Psychology, University of Guelph, Guelph, ON, Canada. Alice Virani is with the Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Elizabeth S. Wilcox is with the School of Population and Public Health, University of British Columbia
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50
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Abstract
Whole-genome sequencing has opened the way for investigating the dynamics and genomic evolution of bacterial pathogens during the colonization and infection of humans. The application of this technology to the longitudinal study of adaptation in an infected host--in particular, the evolution of drug resistance and host adaptation in patients who are chronically infected with opportunistic pathogens--has revealed remarkable patterns of convergent evolution, suggestive of an inherent repeatability of evolution. In this Review, we describe how these studies have advanced our understanding of the mechanisms and principles of within-host genome evolution, and we consider the consequences of findings such as a potent adaptive potential for pathogenicity. Finally, we discuss the possibility that genomics may be used in the future to predict the clinical progression of bacterial infections and to suggest the best option for treatment.
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