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Sadighi A, Aghamohammadpour Z, Sadeghpour Heravi F, Somi MH, Masnadi Shirazi Nezhad K, Hosseini S, Bahman Soufiani K, Ebrahimzadeh Leylabadlo H. The protective effects of Helicobacter pylori: A comprehensive review. JOURNAL OF RESEARCH IN CLINICAL MEDICINE 2024; 12:17. [DOI: 10.34172/jrcm.34509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 10/15/2023] [Indexed: 01/03/2025] Open
Abstract
Previous reports have estimated that approximately half of the world’s population is infected with Helicobacter pylori, the most prevalent infectious agent responsible for gastrointestinal illnesses. Due to the life-threatening effects of H. pylori infections, numerous studies have focused on developing medical therapies for H. pylori infections, while the commensal relationship and positive impacts of this bacterium on overall human health have been largely overlooked. The inhibitory efficacy of H. pylori on the progression of several chronic inflammatory disorders and gastrointestinal diseases has recently raised concerns about whether this bacterium should be eradicated in affected individuals or maintained in an appropriate balance depending on the patient’s condition. This review investigates the beneficial effects of H. pylori in preventing various diseases and discusses the potential association of conditions such as inflammatory disorders with the absence of H. pylori.
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Affiliation(s)
- Ali Sadighi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Aghamohammadpour
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Samaneh Hosseini
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Katayoun Bahman Soufiani
- Department of Laboratory Sciences and Microbiology, Faculty of Medical Sciences, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran
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Dong Y, Gai Z, Han M, Xu J, Zou K. Reduction in Serum Concentrations of Uremic Toxins Driven by Bifidobacterium Longum Subsp. Longum BL21 is Associated with Gut Microbiota Changes in a Rat Model of Chronic Kidney Disease. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10293-5. [PMID: 38829564 DOI: 10.1007/s12602-024-10293-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2024] [Indexed: 06/05/2024]
Abstract
Gut microbiota dysbiosis and consequent impairment of gut barrier function, culminating in elevated levels of uremic toxins, are prevalent in chronic kidney disease (CKD) patients. These toxins, notably indoxyl sulphate (IS), indole-3-acetic acid (IAA), and trimethylamine oxide (TMAO), are implicated in a spectrum of CKD-related complications, including cardiovascular disease, bone and mineral disorders, and inflammation. The specific impacts of various probiotics on these CKD manifestations remain unexplored. This study delved into the potential of dietary probiotic interventions, particularly Bifidobacterium longum subsp. longum BL21, to modulate gut microbiota and mitigate metabolic disorders in a CKD rat model. Over a six-week period, we administered a dietary regimen of BL21 and conducted comprehensive analyses, including serum uremic toxin quantification and 16S rRNA gene sequencing, to systematically profile gut microbial alterations at the phylogenetic level. Our findings reveal that BL21 intervention significantly ameliorated CKD-induced disruptions in gut microbial populations, enhancing both microbial richness and the relative abundance of key taxa. Importantly, BL21 appeared to exert its beneficial effects by modulating the abundance of crucial species such as Barnesiella and Helicobacter. Functionally, the intervention markedly normalized serum levels of IS, IAA, and TMAO, while potentially attenuating p-cresol sulphate (PCS) and p-cresol glucuronide (PCG) concentrations. Consequently, BL21 demonstrated efficacy in regulating gut microbiota and curtailing the accumulation of uremic toxins. Our results advocate for the utilization of BL21 as a dietary intervention to diminish serum uremic toxins and re-establish gut microbiota equilibrium at the phylogenetic level, underscoring the promise of probiotic strategies in the management of CKD.
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Affiliation(s)
- Yao Dong
- Germline Stem Cells and Microenvironment Lab, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- Stem Cell Research and Translation Center, Nanjing Agricultural University, Nanjing, 210095, China
| | - Zhonghui Gai
- Department of Research and Development, Wecare Probiotics Co., Ltd, Suzhou, 215200, China
| | - Mei Han
- Department of Food Quality and Safety, Shanghai Business School, Shanghai, 200235, China
| | - Jiaqi Xu
- Department of Research and Development, Wecare Probiotics Co., Ltd, Suzhou, 215200, China
| | - Kang Zou
- Germline Stem Cells and Microenvironment Lab, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
- Stem Cell Research and Translation Center, Nanjing Agricultural University, Nanjing, 210095, China.
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Wang C, Yao M, Zhong H, Meena SS, Shu F, Nie S, Xie M. Natural foods resources and dietary ingredients for the amelioration of Helicobacter pylori infection. Front Med (Lausanne) 2023; 10:1324473. [PMID: 38131043 PMCID: PMC10734694 DOI: 10.3389/fmed.2023.1324473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric-persistent pathogen that can cause peptic ulcer disease, gastric cancer, and mucosal-associated lymphoid tissue lymphoma. This pathogen is commonly treated with antibiotic-based triple or quadruple therapy. However, antibiotic therapy could result in the bacterial resistance, imbalance of gut microbiota, and damage to the liver and kidneys, etc. Therefore, there is an urgent need for alternative therapeutic strategies. Interestingly, natural food resources, like vegetables, fruits, spices, and edible herbs, have potent inhibitory effects on H. pylori. In this review, we systematically summarized these foods with supporting evidence from both animal and clinical studies. The results have indicated that natural foods may possess temporary inhibition effect on H. pylori rather than durable eradication, and may help to reduce H. pylori colonization, enhance the effect of antibiotics and modulate the host's immune response.
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Affiliation(s)
- Chengyuan Wang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Meixiang Yao
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Hongguang Zhong
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Stephene S. Meena
- Jiangzhong Cancer Research, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Fuxing Shu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
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Avalueva EB, Serkova MY, Sitkin SI. <i>Helicobacter pylori</i>. The survival strategy of a commensal symbiont in the <i>Homo sapiens</i> population. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:102-108. [DOI: 10.31146/1682-8658-ecg-193-9-102-108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Несмотря на крайне высокую степень инфицированности Helicobacter pylori в популяции Homo sapiens, подавляющее большинство инфицированных являются бессимптомными носителями. Широкое распространение инфекции H. pylori среди лиц без признаков патологии и низкая заболеваемость при хронической колонизации слизистой оболочки желудка указывают на то, что H. pylori с большей вероятностью является условно-патогенным микроорганизмом или патобионтом. Популяционная ликвидация инфекции H. pylori существенно снизила заболеваемость инфекцией H. pylori, однако появление устойчивости к противомикробным препаратам привело к их неэффективности.
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Affiliation(s)
- E. B. Avalueva
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - M. Yu. Serkova
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation; Almazov National Medical Research Centre
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Miller AK, Williams SM. Helicobacter pylori infection causes both protective and deleterious effects in human health and disease. Genes Immun 2021; 22:218-226. [PMID: 34244666 PMCID: PMC8390445 DOI: 10.1038/s41435-021-00146-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/18/2021] [Accepted: 06/28/2021] [Indexed: 02/06/2023]
Abstract
Infection with Helicobacter pylori (H. pylori) is necessary but not sufficient for the development of gastric cancer, the third leading cause of cancer death globally. H. pylori infection affects over half of people globally; however, it does not affect populations uniformly. H. pylori infection rates are declining in western industrialized countries but are plateauing in developing and newly industrialized countries where gastric cancer is most prevalent. Despite H. pylori infection being the primary causative agent for gastric cancer, H. pylori infection can also cause other effects, detrimental or beneficial, throughout an individual's life, with the beneficial effects often being seen in childhood and the deleterious effects in adulthood. H. pylori is an ancient bacterium and its likelihood of affecting disease or health is dependent on both human and bacterial genetics that have co-evolved over millennia. In this review, we focus on the impact of infection and its genetic bases in different populations and diseases throughout an individual's lifespan, highlighting the benefits of individualized treatment and argue that universal eradication of H. pylori in its host may cause more harm than good for those infected with H. pylori.
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Affiliation(s)
- Anna K Miller
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH
| | - Scott M Williams
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH,Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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Compo NR, Mieles-Rodriguez L, Gomez DE. Fecal Bacterial Microbiota of Healthy Free-Ranging, Healthy Corralled, and Chronic Diarrheic Corralled Rhesus Macaques ( Macaca mulatta). Comp Med 2021; 71:152-165. [PMID: 33814032 DOI: 10.30802/aalas-cm-20-000080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
A clinical challenge to nearly every primate facility in North America is chronic idiopathic diarrhea (CID), the pathogenesis of which has yet to be fully elucidated. However, wild macaques appear resistant to CID, a trend that we observed in the free-ranging population of the Caribbean Primate Research Center. The gastrointestinal microbiota has been shown to have a significant role in the pathogenesis of disease and in maintaining normal health and development of the gut. In humans, chronic diarrhea is associated with alteration of the gut microbiota, which has lower bacterial diversity than does the microbiota of healthy humans. The current study was designed to describe and compare the fecal bacterial microbiota of healthy corralled, CID corralled, and healthy, free-ranging macaques. Fresh fecal samples were collected from healthy corralled (HC; n = 30) and CID (n = 27) rhesus macaques and from healthy macaques from our free-ranging colony (HF; n = 43). We excluded macaques that had received antibiotics during the preceding 60 d (90 d for healthy animals). Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced and compared with known databases. The relative abundance of Proteobacteria was higher in CID animals than HC animals, but otherwise few differences were found between these 2 groups. HF macaques were differentially enriched with Christensenellaceae and Helicobacter, which are highly associated with a 'healthy' gut in humans, as compared to corralled animals, whereas CID animals were enriched with Proteobacteria, which are associated with dysbiosis in other species. These results indicate that environment has a greater influence than health status on the gut microbiota. Furthermore, the current data provided targets for future studies on potential clinical interventions, such as probiotics and fecal transplants.
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Affiliation(s)
- Nicole R Compo
- Caribbean Primate Research Center, Unit of Comparative Medicine, University of Puerto Rico, Sabana Seca, Puerto Rico; SoBran Bioscience, Norfolk, Virginia;,
| | - Luis Mieles-Rodriguez
- Caribbean Primate Research Center, Unit of Comparative Medicine, University of Puerto Rico, Sabana Seca, Puerto Rico
| | - Diego E Gomez
- Department of Large Animal Clinical Studies, College of Veterinary Medicine, University of Florida, Gainesville, Florida; Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
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Reshetnyak VI, Burmistrov AI, Maev IV. Helicobacter pylori: Commensal, symbiont or pathogen? World J Gastroenterol 2021; 27:545-560. [PMID: 33642828 PMCID: PMC7901052 DOI: 10.3748/wjg.v27.i7.545] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/28/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
This review considers the data on Helicobacter pylori (H. pylori), which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal diseases. The majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis, peptic ulcer disease, and gastric cancer, as well as methods for its eradication. However, in recent years, there have been more and more studies which have suggested that H. pylori has a beneficial, or potentially positive, effect on the human body. The authors have attempted to objectively analyze the information accumulated in the literature on H. pylori. Some studies consider it as one of the recently identified human bacterial pathogens, and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal (commensal from French to English is a table companion) or even a symbiont. The presented data discussing the presence or absence of the effect of H. pylori on human health suggest that there is an apparent ambiguity of the problem. The re-assessment of the data available on H. pylori infection is important in order to answer the question of whether it is necessary to create a program of mass H. pylori eradication or to apply a more personalized approach to treating patients with H. pylori-associated gastrointestinal diseases and to perform eradication therapy.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Alexandr Igorevich Burmistrov
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Crowley E, Hussey S. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:275-292.e12. [DOI: 10.1016/b978-0-323-67293-1.00027-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Pre-existing Helicobacter pylori serum IgG enhances the vibriocidal antibody response to CVD 103-HgR live oral cholera vaccine in Malian adults. Sci Rep 2020; 10:16871. [PMID: 33037244 PMCID: PMC7547695 DOI: 10.1038/s41598-020-71754-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 08/17/2020] [Indexed: 02/07/2023] Open
Abstract
Accumulating evidence indicates that persistent Helicobacter pylori gastric infection influences immune responses to oral enteric vaccines. We studied the association between pre-existing H. pylori serum IgG and serum pepsinogens levels (PGs) as markers of gastric inflammation and the immune response to single-dose live oral cholera vaccine CVD 103-HgR in Malian adults. Baseline sera obtained during a phase 2 safety/immunogenicity clinical trial of cholera vaccine CVD 103-HgR among 93 healthy Malian adults were tested for H. pylori IgG antibodies and PGI and PGII levels using enzyme linked immunosorbent assays. Overall 74/93 (80%) vaccine recipients were H. pylori IgG seropositive at baseline. Vibriocidal antibody seroconversion (≥ fourfold increase 14 days following administration of CVD 103-HgR compared to baseline) among vaccine recipients was 56%. However, vibriocidal antibody seroconversion was markedly higher among H. pylori seropositives than seronegatives 64% vs. 26% (p = 0.004); adjusted relative risk: 2.20 (95% confidence intervals 1.00–4.80; p = 0.049). Among H. pylori seropositive vaccine recipients, there were no significant associations between PGI, PGII and PGI:PGII levels and vibriocidal seroconversion. The enhanced seroconversion to oral cholera vaccine CVD 103-HgR among H. pylori seropositive African adults provides further evidence of the immunomodulating impact of H. pylori on oral vaccine immunogenicity.
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Yu X, Wang Z, Wang L, Meng X, Zhou C, Xin Y, Sun W, Dong Q. Gastric hyperplastic polyps inversely associated with current Helicobacter pylori infection. Exp Ther Med 2020; 19:3143-3149. [PMID: 32256802 DOI: 10.3892/etm.2020.8567] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 01/30/2020] [Indexed: 12/26/2022] Open
Abstract
The incidence of gastric hyperplastic polyps (HPs) has been on the rise in recent years. The contribution of Helicobacter pylori infection to this trend has remained to be elucidated. The present study aimed to explore the association between HPs and H. pylori in China, an area with a high infection rate of H. pylori. In order to study trends of HPs and H. pylori infection over the past decades, cases encountered from 2009 to 2018 were assessed and a total of 109,150 consecutive patients who underwent esophagogastroduodenoscopy at Qingdao Municipal Hospital (Qingdao, China) were enrolled. The incidence of HPs and the prevalence of H. pylori were determined and their correlation was explored. Gastric HPs were detected in 1,497 patients (1.6%) who received gastric biopsies. The incidence of HPs exhibited a rising trend, with a ~4-fold increase in the annual detection rate from 2009 to 2018. The prevalence of H. pylori infection was inversely associated with the prevalence of HPs (adjusted odds ratio, 0.66). The prevalence of H. pylori in the examined cohort decreased with time (r=-0.76, P=0.011). The decreasing trend of H. pylori infection was negatively correlated with the rising trend of HPs (r=-0.64, P=0.048), further indicating an inverse association between them. The difference in the prevalence of HPs between H. pylori-negative and -positive patients increased with age (r=0.80, P=0.018). The age-associated increase was slower in H. pylori-infected patients. The decline in H. pylori infection with time appeared to not be associated with the birth cohort effect, suggesting the decline was not caused by exposure to environmental factors during an early period of life. The present results indicated that the incidence of gastric HPs increased with the decline in H. pylori infection, demonstrating an inverse association between the occurrence of HPs and the infection.
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Affiliation(s)
- XinJuan Yu
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - ZhengQiang Wang
- Clinical Laboratory, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - LiLi Wang
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - XinYing Meng
- Department of Health Care, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - ChangHong Zhou
- Department of Health Care, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - YongNing Xin
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - WeiLi Sun
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China.,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - QuanJiang Dong
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China.,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
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Salama RI, Emara MH, Mostafa HM, Abd-Elsalam S, Alnabawy SM, Elshweikh SA, Zaghloul MS. Helicobacter pylori infection and risk of salmonella infection. Medicine (Baltimore) 2019; 98:e14335. [PMID: 30732157 PMCID: PMC6380853 DOI: 10.1097/md.0000000000014335] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H pylori) infection is the most frequent infection worldwide and it has been postulated that it predisposes to multiple enteric pathogens and diarrheal diseases. Salmonella infection is common in tropical and under developed communities and is associated with wide range of diseases from gastroenteritis to typhoid fever. This study aimed at detecting the impact of H pylori infection on the incidence of salmonella infections.The study participants were sampled from cohorts of patients in four university hospitals in different Egyptian Governorates. Their age ranged from 20 to 59 years and followed up for a rising Widal test. Case patients (n = 109) were subjects who visited the outpatient clinic because of diarrhea and typhoid like illness. They were either positive for H pylori stool antigen (n = 53) or negative to it (n = 56). All patients were subjected to thorough history taking, clinical examination, routine laboratory investigations, abdominal ultrasonography, H pylori stool antigen detection, and serial Widal test assay.The proportion of salmonella-infected subjects was lower among case patients with H pylori infection (22.6%) than among those negative for H pylori (33.9%) albeit not statistically significant (adjusted odds ratio [OR], 0.57; 95% confidence interval [CI], 0.24-1.33; P = .21). The association persisted nonsignificant after adjusting for sociodemographic variables (adjusted OR, 0.5; 95% CI, 0.18-1.39; P = .18). In a multivariate analysis that adjusted for sex, dietary habits, socioeconomic status, and educational level subjects who eat outdoors were associated with a significantly greater risk of salmonella typhi infection.Our findings suggest that there is no association between H pylori infection and salmonella infection in patients presented with typhoid fever or typhoid like illness.
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Affiliation(s)
- Rasha I. Salama
- Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig
| | - Mohamed H. Emara
- Hepatology, Gastroenetrology and Infectious Diseases Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh
| | - Hanan M. Mostafa
- Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria
| | | | | | | | - Mariam Salah Zaghloul
- Hepatology, Gastroenetrology and Infectious Diseases Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh
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12
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Chen Z, Yeoh YK, Hui M, Wong PY, Chan MCW, Ip M, Yu J, Burk RD, Chan FKL, Chan PKS. Diversity of macaque microbiota compared to the human counterparts. Sci Rep 2018; 8:15573. [PMID: 30349024 PMCID: PMC6197227 DOI: 10.1038/s41598-018-33950-6] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 10/10/2018] [Indexed: 02/08/2023] Open
Abstract
Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.
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Affiliation(s)
- Zigui Chen
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Yun Kit Yeoh
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Mamie Hui
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Po Yee Wong
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Martin C W Chan
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Margaret Ip
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, and CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Robert D Burk
- Departments of Pediatrics, Microbiology and Immunology, Epidemiology and Population Health, and Obstetrics, Gynecology and Woman's Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Francis K L Chan
- Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Paul K S Chan
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. .,Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China.
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Sitaraman R. Prokaryotic horizontal gene transfer within the human holobiont: ecological-evolutionary inferences, implications and possibilities. MICROBIOME 2018; 6:163. [PMID: 30223892 PMCID: PMC6142633 DOI: 10.1186/s40168-018-0551-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 09/05/2018] [Indexed: 05/26/2023]
Abstract
The ubiquity of horizontal gene transfer in the living world, especially among prokaryotes, raises interesting and important scientific questions regarding its effects on the human holobiont i.e., the human and its resident bacterial communities considered together as a unit of selection. Specifically, it would be interesting to determine how particular gene transfer events have influenced holobiont phenotypes in particular ecological niches and, conversely, how specific holobiont phenotypes have influenced gene transfer events. In this synthetic review, we list some notable and recent discoveries of horizontal gene transfer among the prokaryotic component of the human microbiota, and analyze their potential impact on the holobiont from an ecological-evolutionary viewpoint. Finally, the human-Helicobacter pylori association is presented as an illustration of these considerations, followed by a delineation of unresolved questions and avenues for future research.
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Affiliation(s)
- Ramakrishnan Sitaraman
- Department of Biotechnology, TERI School of Advanced Studies, 10 Institutional Area, Vasant Kunj, New Delhi, 110070, India.
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14
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Li J, Perez-Perez GI. Helicobacter pylori the Latent Human Pathogen or an Ancestral Commensal Organism. Front Microbiol 2018; 9:609. [PMID: 29666614 PMCID: PMC5891615 DOI: 10.3389/fmicb.2018.00609] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/15/2018] [Indexed: 12/15/2022] Open
Abstract
We dedicated this review to discuss Helicobacter pylori as one of the latest identified bacterial pathogens in humans and whether its role is mainly as a pathogen or a commensal. Diseases associated with this bacterium were highly prevalent during the 19th century and gradually have declined. Most diseases associated with H. pylori occurred in individuals older than 40 years of age. However, acquisition of H. pylori occurs mainly in young children inside the family setting. Prevalence and incidence of H. pylori has had a dramatic change in the last part of the 20th century and beginning of the 21th century. In developed countries there is a clear interruption of transmission and the lowest prevalence is observed in children younger than 10 years in these countries. A similar decline is observed but not at the same level in developing countries. Here we discuss the impact of the presence or absence of H. pylori in the health status of humans. We also discuss whether it is necessary or not to establish H. pylori eradication programs on light of the current decline in H. pylori prevalence.
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Affiliation(s)
- Jackie Li
- Department of Medicine, School of Medicine, New York University, New York, NY, United States
| | - Guillermo I Perez-Perez
- Department of Medicine, School of Medicine, New York University, New York, NY, United States.,Department of Medicine and Microbiology, School of Medicine, New York University, New York, NY, United States
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15
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Diet and Helicobacter pylori infection. GASTROENTEROLOGY REVIEW 2016; 11:150-154. [PMID: 27713775 PMCID: PMC5047973 DOI: 10.5114/pg.2016.61487] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 12/24/2015] [Indexed: 12/25/2022]
Abstract
Helicobacter pylori infection has accompanied man for thousands of years. In some infected patients, a complex and dynamic pathogen-host reaction triggers pathogenic pathways resulting in development, inter alia, of atrophic gastritis, peptic ulcer disease (both gastric and duodenal), gastric adenocarcinoma, and MALT lymphoma. Large-scale eradication therapy is associated with a rapid increase in antibiotic resistance, gut flora composition disturbances, and increased risk of development, inter alia, of paediatric infectious diarrhoeas, atopic diseases, and oesophageal adenocarcinoma. Our diet contains many substances with potent antibacterial activity against H. pylori. Dietary interventions enable a decrease in H. pylori colonisation and result in a decrease in gastritis prevalence, thus potentially lowering the risk of gastric adenocarcinoma development.
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16
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Fuenmayor-Boscán AD, Hernández IM, Valero KJ, Paz AM, Sandrea LB, Rivero Z. Association between Helicobacter pylori and intestinal parasites in an Añu indigenous community of Venezuela. Indian J Gastroenterol 2016; 35:106-12. [PMID: 27138927 DOI: 10.1007/s12664-016-0641-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 03/13/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Helicobacter pylori (Hp) and enteroparasite infections are highly prevalent in populations with poor living conditions, like the Amerindian communities. Identifying associations between both types of infectious agents could help to detect shared risk factors or transmission routes in these minority ethnic groups. Therefore, the prevalence and association between Hp and enteroparasites were investigated in an indigenous community whose living conditions favor such infectious diseases. METHODS Seropositivity (anti-Hp-specific IgG) and active infection (stool antigen test), intestinal parasitosis (direct and concentrated coproparasitological test, methylene blue, and Kinyoun stains), and risk factors for fecal-oral transmission were determined in 167 children and 151 adults of the Añu indigenous community living at the Sinamaica Lagoon, in Venezuela. RESULTS A high rate of Hp infection (seropositivity and active infection) and enteroparasitosis was evidenced, as expected. Some significant associations were detected: direct associations between Hp and polyparasitic infection, helminths, and protozoan (particularly in children); inverse association between Hp and Giardia lamblia. No shared epidemiological factors were identified for Hp and the detected intestinal parasites, probably due to overlapping factors. CONCLUSION Direct associations detected support the participation of the fecal-oral route in the transmission of the involved infectious agents. Inverse relationship (Hp) and G. lamblia may suggest the existence of antagonistic interactions between them. Further research is required to elucidate the mechanisms underlying these associations.
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Affiliation(s)
- Alisbeth D Fuenmayor-Boscán
- Facultad de Medicina, Departamento de Microbiología. Escuela de Bioanálisis, Universidad del Zulia, Maracaibo, Venezuela.
| | - Ileana M Hernández
- Facultad de Medicina Instituto de Investigaciones Biológicas, Universidad del Zulia, Maracaibo, Venezuela
| | - Kutchynskaya J Valero
- Facultad de Medicina, Departamento de Microbiología. Escuela de Bioanálisis, Universidad del Zulia, Maracaibo, Venezuela
| | - América M Paz
- Facultad de Medicina, Departamento de Microbiología. Escuela de Bioanálisis, Universidad del Zulia, Maracaibo, Venezuela
| | - Lisette B Sandrea
- Facultad de Medicina, Departamento de Microbiología. Escuela de Bioanálisis, Universidad del Zulia, Maracaibo, Venezuela
| | - Zulbey Rivero
- Facultad de Medicina, Departamento de Microbiología. Escuela de Bioanálisis, Universidad del Zulia, Maracaibo, Venezuela
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17
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Kienesberger S, Cox LM, Livanos A, Zhang XS, Chung J, Perez-Perez GI, Gorkiewicz G, Zechner EL, Blaser MJ. Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses. Cell Rep 2016; 14:1395-1407. [PMID: 26854236 DOI: 10.1016/j.celrep.2016.01.017] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/24/2015] [Accepted: 01/02/2016] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a late-in-life human pathogen with potential early-life benefits. Although H. pylori is disappearing from the human population, little is known about the influence of H. pylori on the host's microbiota and immunity. Studying the interactions of H. pylori with murine hosts over 6 months, we found stable colonization accompanied by gastric histologic and antibody responses. Analysis of gastric and pulmonary tissues revealed increased expression of multiple immune response genes, conserved across mice and over time in the stomach and more transiently in the lungs. Moreover, H. pylori infection led to significantly different population structures in both the gastric and intestinal microbiota. These studies indicate that H. pylori influences the microbiota and host immune responses not only locally in the stomach, but distantly as well, affecting important target organs.
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Affiliation(s)
- Sabine Kienesberger
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA; Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria; Institute of Pathology, Medical University of Graz, Graz 8043, Austria.
| | - Laura M Cox
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA; Department of Microbiology, NYU Langone Medical Center, New York, NY 10010, USA
| | - Alexandra Livanos
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA
| | - Xue-Song Zhang
- Department of Microbiology, NYU Langone Medical Center, New York, NY 10010, USA
| | - Jennifer Chung
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA
| | - Guillermo I Perez-Perez
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA; Department of Microbiology, NYU Langone Medical Center, New York, NY 10010, USA
| | - Gregor Gorkiewicz
- Institute of Pathology, Medical University of Graz, Graz 8043, Austria
| | - Ellen L Zechner
- Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria
| | - Martin J Blaser
- Department of Medicine, NYU Langone Medical Center, New York, NY 10010, USA; Department of Microbiology, NYU Langone Medical Center, New York, NY 10010, USA; VA Medical Center, New York, NY 10010, USA.
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18
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den Hollander WJ, Holster IL, van Gilst B, van Vuuren AJ, Jaddoe VW, Hofman A, Perez-Perez GI, Kuipers EJ, Moll HA, Blaser MJ. Intergenerational reduction in Helicobacter pylori prevalence is similar between different ethnic groups living in a Western city. Gut 2015; 64:1200-8. [PMID: 25192563 PMCID: PMC4492887 DOI: 10.1136/gutjnl-2014-307689] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Accepted: 07/25/2014] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Helicobacter pylori colonisation rates in childhood have declined in Western populations, but it is unknown whether this trend is similar in children of non-Western ethnic backgrounds, born in a Western country. We aimed to identify H. pylori status in children, and determine mother-to-child transmission and risk factors for colonisation. DESIGN Antibodies against H. pylori and cytotoxin-associated gene A (CagA) were measured in children participating in a population-based prospective cohort study in Rotterdam, the Netherlands. Information on demographics and characteristics was collected using questionnaires. RESULTS We analysed the serum of 4467 children (mean age 6.2 years±0.4 SD) and compared the results with the H. pylori status of their mothers (available for 3185 children). Overall, 438 (10%) children were H. pylori-positive, of whom 142 (32%) were CagA-positive. Independent risk factors for colonisation were: maternal H. pylori positivity (OR 2.12; 95% CI 1.62 to 2.77), non-Dutch ethnicity (OR 2.05; 95% CI 1.54 to 2.73), female gender (OR 1.47; 95% CI 1.20 to 1.80) and lower maternal education level (OR 1.38; 95% CI 1.06 to 1.79). Comparing mothers and children, we found an intergenerational decrease of 76% and 77% for Hp(+)CagA(-) and Hp(+)CagA(+)-strains, respectively, consistent across all nine ethnic groups studied. Male gender, higher maternal educational level and no older siblings, were independently associated with absence of H. pylori. CONCLUSIONS Although the highest H. pylori and CagA prevalence was found in children of non-Dutch ethnicities, the decreased colonisation rates were uniform across all ethnic groups, implying the importance of environmental factors in H. pylori transmission in modern cities, independent of ethnicity.
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Affiliation(s)
- Wouter J. den Hollander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands,Department of The Generation R Study Group, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - I. Lisanne Holster
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Bianca van Gilst
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Anneke J. van Vuuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Vincent W. Jaddoe
- Department of The Generation R Study Group, Erasmus University Medical Centre, Rotterdam, The Netherlands,Department of Pediatrics, Erasmus University Medical Centre, Rotterdam, The Netherlands,Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Albert Hofman
- Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Guillermo I. Perez-Perez
- Departments of Medicine and Microbiology, New York University Langone Medical Centre, New York, USA
| | - Ernst J. Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands,Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Henriëtte A. Moll
- Department of Pediatrics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Martin J. Blaser
- Departments of Medicine and Microbiology, New York University Langone Medical Centre, New York, USA
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19
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Kalali B, Formichella L, Gerhard M. Diagnosis of Helicobacter pylori: Changes towards the Future. Diseases 2015; 3:122-135. [PMID: 28943614 PMCID: PMC5548244 DOI: 10.3390/diseases3030122] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/18/2015] [Accepted: 06/19/2015] [Indexed: 12/19/2022] Open
Abstract
Since the first evidence demonstrating the dramatically high incidence of H. pylori infection and the subsequent medical challenges it incurs, health management of H. pylori infection has been a high priority for health authorities worldwide. Despite a decreasing rate of infection in western countries, prevalence of H. pylori infection in developing and in some industrial countries is still very high. Whereas treatment and vaccination against H. pylori is a contemporary issue in medical communities, selective treatment and prior high-throughput screening of the subject population is a major concern of health organizations. So far, diagnostic tests are either elaborative and require relatively advanced medical care infrastructure or they do not fulfill the criteria recommended by the Maastricht IV/Florence consensus report. In this review, in light of recent scientific studies, we highlight current and possible future approaches for the diagnosis of H. pylori. We point out that novel non-invasive tests may not only cover the requirements of gold standard methods in H. pylori detection but also offer the potential for risk stratification of infection in a high throughput manner.
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Affiliation(s)
- Behnam Kalali
- Institute of Medical Microbiology, Immunology and Hygiene, TU-Munich, Troger Str.30, 81675 Munich, Germany.
- ImevaX GmbH, Grillparzer Str.18, 81675 Munich, Germany.
| | - Luca Formichella
- Institute of Medical Microbiology, Immunology and Hygiene, TU-Munich, Troger Str.30, 81675 Munich, Germany.
| | - Markus Gerhard
- Institute of Medical Microbiology, Immunology and Hygiene, TU-Munich, Troger Str.30, 81675 Munich, Germany.
- ImevaX GmbH, Grillparzer Str.18, 81675 Munich, Germany.
- German Center for Infection Research (DZIF), Partner site Munich, Troger Str.30, 81675 Munich, Germany.
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20
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Leal-Lopes C, Velloso FJ, Campopiano JC, Sogayar MC, Correa RG. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies. J Diabetes Res 2015; 2015:284680. [PMID: 26347203 PMCID: PMC4544440 DOI: 10.1155/2015/284680] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 07/09/2015] [Indexed: 12/12/2022] Open
Abstract
The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities.
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Affiliation(s)
- Camila Leal-Lopes
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Fernando J. Velloso
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Julia C. Campopiano
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Mari C. Sogayar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Ricardo G. Correa
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
- *Ricardo G. Correa:
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21
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Blaser MJ, Webb GF. Host demise as a beneficial function of indigenous microbiota in human hosts. mBio 2014; 5:e02262-14. [PMID: 25516618 PMCID: PMC4271553 DOI: 10.1128/mbio.02262-14] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 11/14/2014] [Indexed: 01/12/2023] Open
Abstract
UNLABELLED The age structure of human populations is exceptional among animal species. Unlike with most species, human juvenility is extremely extended, and death is not coincident with the end of the reproductive period. We examine the age structure of early humans with models that reveal an extraordinary balance of human fertility and mortality. We hypothesize that the age structure of early humans was maintained by mechanisms incorporating the programmed death of senescent individuals, including by means of interactions with their indigenous microorganisms. First, before and during reproductive life, there was selection for microbes that preserve host function through regulation of energy homeostasis, promotion of fecundity, and defense against competing high-grade pathogens. Second, we hypothesize that after reproductive life, there was selection for organisms that contribute to host demise. While deleterious to the individual, the presence of such interplay may be salutary for the overall host population in terms of resource utilization, resistance to periodic diminutions in the food supply, and epidemics due to high-grade pathogens. We provide deterministic mathematical models based on age-structured populations that illustrate the dynamics of such relationships and explore the relevant parameter values within which population viability is maintained. We argue that the age structure of early humans was robust in its balance of the juvenile, reproductive-age, and senescent classes. These concepts are relevant to issues in modern human longevity, including inflammation-induced neoplasia and degenerative diseases of the elderly, which are a legacy of human evolution. IMPORTANCE The extended longevity of modern humans is a very recent societal artifact, although it is inherent in human evolution. The age structure of early humans was balanced by fertility and mortality, with an exceptionally prolonged juvenility. We examined the role of indigenous microbes in early humans as fundamental contributors to this age structure. We hypothesize that the human microbiome evolved mechanisms specific to the mortality of senescent individuals among early humans because their mortality contributed to the stability of the general population. The hypothesis that we present provides new bases for modern medical problems, such as inflammation-induced neoplasia and degenerative diseases of the elderly. We postulate that these mechanisms evolved because they contributed to the stability of early human populations, but their legacy is now a burden on human longevity in the changed modern world.
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Affiliation(s)
| | - Glenn F Webb
- Department of Mathematics, Vanderbilt University, Nashville, Tennessee, USA
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22
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Kodaman N, Sobota RS, Mera R, Schneider BG, Williams SM. Disrupted human-pathogen co-evolution: a model for disease. Front Genet 2014; 5:290. [PMID: 25202324 PMCID: PMC4142859 DOI: 10.3389/fgene.2014.00290] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Accepted: 08/05/2014] [Indexed: 02/06/2023] Open
Abstract
A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease etiology. We discuss our model in the context of three pathogens, Helicobacter pylori, Mycobacterium tuberculosis and human papillomavirus, and generalize the conditions under which it may be applicable.
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Affiliation(s)
- Nuri Kodaman
- Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA ; Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University Medical Center Nashville, TN, USA
| | - Rafal S Sobota
- Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA ; Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University Medical Center Nashville, TN, USA
| | - Robertino Mera
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA
| | - Barbara G Schneider
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA
| | - Scott M Williams
- Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA
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23
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Malnick SDH, Melzer E, Attali M, Duek G, Yahav J. Helicobacter pylori: friend or foe? World J Gastroenterol 2014; 20:8979-85. [PMID: 25083071 PMCID: PMC4112870 DOI: 10.3748/wjg.v20.i27.8979] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/23/2014] [Accepted: 04/21/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.
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24
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He C, Yang Z, Lu NH. Helicobacter pylori infection and diabetes: Is it a myth or fact? World J Gastroenterol 2014; 20:4607-4617. [PMID: 24782613 PMCID: PMC4000497 DOI: 10.3748/wjg.v20.i16.4607] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 02/10/2014] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most common human bacterial pathogens, and infection causes a wide array of gastric disorders, including simple gastritis, peptic ulcers and gastric malignancies. Gastrointestinal inflammation caused by H. pylori can influence the absorption of glucose and lipids, which are also abnormal in diabetes mellitus. Type 2 diabetes mellitus (T2DM), formerly known as non-insulin-dependent diabetes mellitus or adult-onset diabetes, is a metabolic disorder that is characterized by high levels of blood glucose resulting from insulin resistance and relative insulin deficiency. It is an emerging pandemic and is rapidly becoming a serious threat to public health. Emerging data now indicate a strong relationship between H. pylori infection and the incidence of T2DM. The mechanisms underlying the pathogenesis of diabetes are complex, involving insulin resistance, chronic inflammation, insulin secretion deficiency as a result of pancreas β-cell dysfunction, glucotoxicity, and lipotoxicity. H. pylori infection is known to be involved in the pathogenesis of insulin resistance, and the growing awareness of its role in diabetes is important for the early detection of glucose dysregulation and prevention of T2DM in high-risk communities. This review probes the possible relationship between H. pylori and diabetes according to epidemiological surveys and discusses putative mechanisms underlying this correlation.
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25
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The Relation between Helicobacter pylori Infection and Acute Bacterial Diarrhea in Children. Int J Pediatr 2014; 2014:191643. [PMID: 24696690 PMCID: PMC3950475 DOI: 10.1155/2014/191643] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Revised: 01/11/2014] [Accepted: 01/12/2014] [Indexed: 01/04/2023] Open
Abstract
Background. H. pylori infection leads to chronic gastritis in both children and adults. But recently, there are arising theories of its protective effect in diarrheal diseases. Aim. To explore the prevalence of H. pylori infection in children with bacterial diarrhea and compare it with healthy controls. Patients and Methods. Two matched groups consisted of 122 consecutive children, aged 24–72 months old, with acute bacterial diarrhea, who had Shigellosis (N = 68) and Salmonellosis (N = 54) as patients group and 204 healthy asymptomatic children as control group enrolled in this study. Results. The prevalence of H. pylori infection in healthy control children was significantly higher than in patients group, (odds ratio = 3.6, 95% CI: 1.33–9.5, P = 0.007). In our study, only 2/54 Salmonella infected patients and 3/68 of Shigellosis had evidence of H. pylori infection, while normal control children had 27/204 infected individuals. Conclusion. H. pylori infection may play a protective role against bacterial diarrhea in children. So it is important to consider all of the positive and negative aspects of H. pylori infection before its eradication.
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26
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Queiroz DMM, Rocha AMC, Crabtree JE. Unintended consequences of Helicobacter pylori infection in children in developing countries: iron deficiency, diarrhea, and growth retardation. Gut Microbes 2013; 4:494-504. [PMID: 23988829 PMCID: PMC3928161 DOI: 10.4161/gmic.26277] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [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 infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review.
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Affiliation(s)
- Dulciene MM Queiroz
- Laboratory of Research in Bacteriology; Faculdade de Medicina; Universidade Federal de Minas Gerais; Belo Horizonte, Brazil
| | - Andreia MC Rocha
- Laboratory of Research in Bacteriology; Faculdade de Medicina; Universidade Federal de Minas Gerais; Belo Horizonte, Brazil
| | - Jean E Crabtree
- Leeds Institute Molecular Medicine; St. James’s University Hospital; University of Leeds; Leeds, UK,Correspondence to: Jean E Crabtree,
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Ciccarelli S, Stolfi I, Caramia G. Management strategies in the treatment of neonatal and pediatric gastroenteritis. Infect Drug Resist 2013; 6:133-61. [PMID: 24194646 PMCID: PMC3815002 DOI: 10.2147/idr.s12718] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as "food supplement," seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of "doing the least": oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.
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Affiliation(s)
- Simona Ciccarelli
- Neonatal Intensive Care Unit, Sapienza University of Rome, Rome, Italy
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Is Helicobacter pylori good or bad? Eur J Clin Microbiol Infect Dis 2012; 32:301-4. [PMID: 23132690 DOI: 10.1007/s10096-012-1773-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Accepted: 10/23/2012] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori remains a controversial organism with regards to humans, with its epidemiology still being unclear nearly two decades after its discovery. The association between H. pylori infection and subsequent development of chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue (MALT) lymphoma has been well established. Current studies, however, suggest that fewer than 20 % of all infected patients will develop any consequences from their infection. Hence, should the infection be considered a disease not at all or, on the contrary, is the microorganism harmful in only some circumstances? This article attempts to weigh the currently available evidence supporting that H. pylori may be good and not always bad.
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Dore MP, Fanciulli G, Tomasi PA, Realdi G, Delitala G, Graham DY, Malaty HM. Gastrointestinal symptoms and Helicobacter pylori infection in school-age children residing in Porto Torres, Sardinia, Italy. Helicobacter 2012; 17:369-73. [PMID: 22967120 DOI: 10.1111/j.1523-5378.2012.00955.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Helicobacter pylori infection is typically acquired in childhood, and following the acute event, it is thought that most infections remain asymptomatic. H. pylori has been suggested to protect against diarrhea in childhood. AIM To examine the role of H. pylori in gastrointestinal symptoms in children. MATERIALS AND METHODS A cross-sectional sero-epidemiologic study was conducted in Porto Torres, Sardinia, Italy. Demographic information, socioeconomic factors, and the frequency of upper gastrointestinal symptoms during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn, halitosis, slow digestion, belching, and weight loss) were evaluated by a questionnaire. H. pylori status was determined by ELISA. RESULTS Approximately 95% (N = 1741) of school children between the age of 6 and 15 years from Porto Torres participated. The sero-prevalence of H. pylori infection was 13.3% (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting (odds ratio (OR) = 2.2 (95% CI = 1.2-5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3-2.8)) were each significantly associated with H. pylori infection, and these associations remained significant after controlling for other study variables. There was no significant association between H. pylori and abdominal pain or heartburn (p > .25). CONCLUSIONS The study does not support either a role of H. pylori infection in abdominal pain in children or a protective role against diarrheal illnesses or nausea/vomiting.
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Affiliation(s)
- Maria P Dore
- Dipartimento di Medicina Clinica Sperimentale ed Oncologica, University of Sassari, Sassari, Italy.
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Abstract
It is becoming increasingly clear that our residential microbes, the key constituents in the human microbiome, are centrally involved in many aspects of our physiology. In particular, the ancient and dominant gastric bacteria Helicobacter pylori are highly interactive with human physiology. In modern times, H. pylori has been disappearing, which consequently affects the interactions between luminal bacteria and epithelial, lymphoid, and neuroendocrine cells. A growing body of evidence indicates that H. pylori protects against childhood-onset asthma, probably through the gastric recruitment of regulatory T cells. The phenomenon of disappearing ancient microbiota may be a general paradigm driving the diseases of modernity.
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Chen Y, Blaser MJ. Association between gastric Helicobacter pylori colonization and glycated hemoglobin levels. J Infect Dis 2012; 205:1195-202. [PMID: 22427676 PMCID: PMC3308905 DOI: 10.1093/infdis/jis106] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Accepted: 11/14/2011] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Few studies have evaluated the potential influence of Helicobacter pylori on biomarkers for diabetes. METHODS We conducted cross-sectional analyses using data from 7417 participants in the National Health and Nutrition Examination Survey (NHANES) III (aged ≥18 years) and 6072 participants in NHANES 1999-2000 (aged ≥3 years) to assess the association between H. pylori and levels of glycosylated hemoglobin (HbA1c). RESULTS There was no association between H. pylori and history of self-reported diabetes. Helicobacter pylori seropositivity, especially H. pylori cagA positivity, was positively associated (P < .01, NHANES III; P = .02, NHANES 1999-2000) with HbA1c levels after excluding individuals with history of diabetes and controlling for potential confounders. There was also a synergistic interaction between H. pylori and higher body mass index (BMI), such that increased levels of HbA1c associated with having both H. pylori and higher BMI were greater than the sum of their individual effects (P for interaction < .01). This interaction was observed consistently in both NHANES III and NHANES 1999-2000 and for H. pylori cagA positivity in NHANES III. CONCLUSIONS The findings indicate a role of H. pylori in impaired glucose tolerance in adults that may be potentiated by higher BMI level.
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Affiliation(s)
- Yu Chen
- Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
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Cohen D, Shoham O, Orr N, Muhsen K. An inverse and independent association between Helicobacter pylori infection and the incidence of shigellosis and other diarrheal diseases. Clin Infect Dis 2011; 54:e35-42. [PMID: 22157171 DOI: 10.1093/cid/cir916] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We examined the association between Helicobacter pylori infection and the incidence of diarrheal diseases. METHODS In a nested case-control study participants were sampled from cohorts of male Israeli soldiers aged 18-21 years, serving in field units and followed up for diarrheal diseases. Case patients (n = 177) were subjects who visited the base clinic because diarrhea and were positive for Shigella sonnei (n = 66), enterotoxigenic Escherichia coli (ETEC) (n = 31) or negative for bacterial pathogens (n = 80; diarrhea of unknown etiology). Controls (n = 418) were subjects who did not suffer from a diarrheal disease during the follow-up. They were matched to case patients by training unit and period. Serum samples were obtained from participants at the beginning of their field training and were tested for anti-H. pylori immunoglobulin (Ig) G and preexisting Shigella sonnei lipopolysaccharide IgG and IgA antibodies using enzyme-linked immunosorbent assay. RESULTS The proportion of H. pylori-infected subjects was significantly lower among case patients with infection of unknown etiology (36.3%) than among controls (56.0%) (adjusted odds ratio [OR], 0.43; 95% confidence interval [CI], .24-.77; P = .005). The proportion of H. pylori-infected subjects among case patients with S. sonnei shigellosis was also significantly lower than in the control group: 36.3% versus 56.0%. The association persisted after adjusting for sociodemographic variables and preexisting S. sonnei serum IgA antibodies (adjusted OR, 0.37; 95% CI, .14-.95; P = .03) and IgG antibodies (adjusted OR, 0.38; 95% CI, .14-.99; P = .04). The direction of the association between H. pylori infection and ETEC diarrhea was similar, albeit not statistically significant. CONCLUSIONS Our findings suggest an active role of H. pylori in protection against diarrheal diseases.
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Affiliation(s)
- Dani Cohen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Israel.
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Delgado-Rosado G, Dominguez-Bello MG, Massey SE. Positive selection on a bacterial oncoprotein associated with gastric cancer. Gut Pathog 2011; 3:18. [PMID: 22078307 PMCID: PMC3228766 DOI: 10.1186/1757-4749-3-18] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Accepted: 11/11/2011] [Indexed: 01/01/2023] Open
Abstract
Background Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI); infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO). The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking.
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Affiliation(s)
- Gisela Delgado-Rosado
- Biology Department, University of Puerto Rico - Rio Piedras, PO Box 23360, San Juan, Puerto Rico, USA 00931.
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Veenemans J, Mank T, Ottenhof M, Baidjoe A, Mbugi EV, Demir AY, Wielders JPM, Savelkoul HFJ, Verhoef H. Protection against diarrhea associated with Giardia intestinalis Is lost with multi-nutrient supplementation: a study in Tanzanian children. PLoS Negl Trop Dis 2011. [PMID: 21666789 DOI: 10.137/journal.pntd.0001158.epub] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Asymptomatic carriage of Giardia intestinalis is highly prevalent among children in developing countries, and evidence regarding its role as a diarrhea-causing agent in these settings is controversial. Impaired linear growth and cognition have been associated with giardiasis, presumably mediated by malabsorption of nutrients. In a prospective cohort study, we aim to compare diarrhea rates in pre-school children with and without Giardia infection. Because the study was conducted in the context of an intervention trial assessing the effects of multi-nutrients on morbidity, we also assessed how supplementation influenced the relationship between Giardia and diarrhoea rates, and to what extent Giardia modifies the intervention effect on nutritional status. METHODS AND FINDINGS Data were collected in the context of a randomized placebo-controlled efficacy trial with 2×2 factorial design assessing the effects of zinc and/or multi-micronutrients on morbidity (n=612; height-for-age z-score <-1.5 SD). Outcomes measures were episodes of diarrhea (any reported, or with ≥3 stools in the last 24 h) and fever without localizing signs, as detected with health-facility based surveillance. Giardia was detected in stool by enzyme-linked immunosorbent assay. Among children who did not receive multi-nutrients, asymptomatic Giardia infection at baseline was associated with a substantial reduction in the rate of diarrhea (HR 0.32; 0.15-0.66) and fever without localizing signs (HR 0.56; 0.36-0.87), whereas no such effect was observed among children who received multi-nutrients (p-values for interaction 0.03 for both outcomes). This interaction was independent of age, HAZ-scores and distance to the research dispensary. There was no evidence that Giardia modified the intervention effect on nutritional status. CONCLUSION Although causality of the Giardia-associated reduction in morbidity cannot be established, multi-nutrient supplementation results in a loss of this protection and thus seems to influence the proliferation or virulence of Giardia or associated intestinal pathogens.
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Affiliation(s)
- Jacobien Veenemans
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands
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Veenemans J, Mank T, Ottenhof M, Baidjoe A, Mbugi EV, Demir AY, Wielders JPM, Savelkoul HFJ, Verhoef H. Protection against diarrhea associated with Giardia intestinalis Is lost with multi-nutrient supplementation: a study in Tanzanian children. PLoS Negl Trop Dis 2011; 5:e1158. [PMID: 21666789 PMCID: PMC3110167 DOI: 10.1371/journal.pntd.0001158] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2010] [Accepted: 03/07/2011] [Indexed: 11/19/2022] Open
Abstract
Background Asymptomatic carriage of Giardia intestinalis is highly prevalent among children in developing countries, and evidence regarding its role as a diarrhea-causing agent in these settings is controversial. Impaired linear growth and cognition have been associated with giardiasis, presumably mediated by malabsorption of nutrients. In a prospective cohort study, we aim to compare diarrhea rates in pre-school children with and without Giardia infection. Because the study was conducted in the context of an intervention trial assessing the effects of multi-nutrients on morbidity, we also assessed how supplementation influenced the relationship between Giardia and diarrhoea rates, and to what extent Giardia modifies the intervention effect on nutritional status. Methods and Findings Data were collected in the context of a randomized placebo-controlled efficacy trial with 2×2 factorial design assessing the effects of zinc and/or multi-micronutrients on morbidity (n = 612; height-for-age z-score <−1.5 SD). Outcomes measures were episodes of diarrhea (any reported, or with ≥3 stools in the last 24 h) and fever without localizing signs, as detected with health-facility based surveillance. Giardia was detected in stool by enzyme-linked immunosorbent assay. Among children who did not receive multi-nutrients, asymptomatic Giardia infection at baseline was associated with a substantial reduction in the rate of diarrhea (HR 0.32; 0.15–0.66) and fever without localizing signs (HR 0.56; 0.36–0.87), whereas no such effect was observed among children who received multi-nutrients (p-values for interaction 0.03 for both outcomes). This interaction was independent of age, HAZ-scores and distance to the research dispensary. There was no evidence that Giardia modified the intervention effect on nutritional status. Conclusion Although causality of the Giardia-associated reduction in morbidity cannot be established, multi-nutrient supplementation results in a loss of this protection and thus seems to influence the proliferation or virulence of Giardia or associated intestinal pathogens. Giardia intestinalis is a well-known cause of diarrhea in industrialized countries. In children in developing countries, asymptomatic infections are common and their role as cause of diarrhea has been questioned. In a cohort of rural Tanzanian pre-school children, we assessed the association between the presence of Giardia at baseline and subsequent diarrhea risk. The study was conducted in the context of a randomised trial assessing the effect of supplementation with zinc and other micro-nutrients on malaria, and half of the children daily received a multi-nutrient supplement. Surprisingly, we found that the presence of Giardia at baseline was associated with a substantial reduction in diarrhea risk. Multivariate statistical analysis showed that this protection could not be explained by differences in age or walking distance to the dispensary between children with and without Giardia. Because we cannot exclude that children differed in other (unmeasured) characteristics, we cannot draw firm conclusions about the causality of the observed association, but our findings support the view that the parasite is not an important cause of diarrhea in highly endemic settings. Striking was that the Giardia-associated protection was lost when children received multi-nutrients. Our data do not provide information about the mechanisms involved, but suggest that multi-nutrients may influence the compositionor pathogenicity of intestinal biota.
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Affiliation(s)
- Jacobien Veenemans
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands
| | - Theo Mank
- Department of Parasitology, Public Health Laboratory, Haarlem, The Netherlands
| | - Maarten Ottenhof
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands
- Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Amrish Baidjoe
- Department of Parasitology, Public Health Laboratory, Haarlem, The Netherlands
| | - Erasto V. Mbugi
- Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Ayse Y. Demir
- Laboratory for Clinical Chemistry and Haematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Jos P. M. Wielders
- Laboratory for Clinical Chemistry and Haematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Huub F. J. Savelkoul
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands
| | - Hans Verhoef
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands
- London School of Hygiene and Tropical Medicine, London, United Kingdom
- * E-mail:
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Dramatic decline in prevalence of Helicobacter pylori and peptic ulcer disease in an endoscopy-referral population. Am J Med 2011; 124:260-4. [PMID: 21396510 DOI: 10.1016/j.amjmed.2010.11.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2010] [Revised: 11/08/2010] [Accepted: 11/11/2010] [Indexed: 12/20/2022]
Abstract
PURPOSE To determine if endoscopic Helicobacter pylori and peptic ulcer disease prevalence has changed over an 11-year period in a rural region. METHODS Current endoscopic records were reviewed and compared with similar data obtained over a time period 11 years earlier at the same institution with regard to H. pylori status, endoscopic findings, microscopic pathologic findings, and medication use. RESULTS There were 251 records reviewed in the current study group (mean age 52.8 years, 59.0% female) and 263 in the previous group (mean age 60.1 years, 56.7% female). H. pylori was positive in 17 (6.8%) in the current study and 173 (65.8%) in the earlier study (P <.0001). Peptic ulcer disease (PUD) was present in 14 (5.6%) in the current study and in 102 (38.8%) in the earlier study (P <.0001). H. pylori was positive in 1 of the 14 PUD patients (7.1%) in the current study and in 78 of 102 (76.5%) in the previous study (P <.0001). CONCLUSIONS Endoscopic H. pylori prevalence in our rural locality has decreased substantially over the past decade and may reflect local overall prevalence trends, although underestimation is likely due to widespread prior noninvasive H. pylori diagnosis and treatment. Endoscopic PUD also has decreased precipitously, possibly related to changes in regional H. pylori characteristics and prolific use of antisecretory agents. Changing geographic trends regarding acid-peptic disease may prompt modification of diagnostic approach and treatment.
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Effect of Helicobacter pylori infection on symptoms of gastroenteritis due to enteropathogenic Escherichia coli in adults. Dig Dis Sci 2011; 56:457-64. [PMID: 20635147 PMCID: PMC4005911 DOI: 10.1007/s10620-010-1309-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Accepted: 06/14/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND Helicobacter pylori can cause hypochlorhydria in some hosts and predispose to diarrheal infections. AIMS We tested the hypothesis that chronic H. pylori infection increases the risk of diarrheal illness due to an acid-sensitive organism: enteropathogenic Escherichia coli (EPEC). METHODS After testing healthy adult volunteers for H. pylori, 19 infected and 26 uninfected subjects had gastric pH probes placed and were given 5-10 × 10(9) EPEC organisms; six had previously received a proton pump inhibitor. We measured diarrhea and created a composite gastroenteritis severity score based on symptoms in the 48 h following exposure. Outcomes were compared using logistic regression and analysis of covariance. RESULTS More H. pylori-infected (36.8%) than H. pylori-uninfected subjects (7.7%) were hypochlorhydric (P = 0.02). Six (31.6%) H. pylori-infected and five H. pylori-uninfected subjects (19.2%) developed diarrhea (P = 0.34). Hypochlorhydria was a strong risk factor for diarrhea [odds ratio (OR) 6.25, confidence interval (CI): 1.29-30.35]. After adjusting for hypochlorhydria and EPEC dose, H. pylori was not associated with diarrhea (OR 0.89, CI: 0.17-4.58). Among those with symptoms, H. pylori-infected subjects had lower gastroenteritis severity score than did H. pylori-uninfected subjects (2.6, CI: 1.9-3.4 versus 1.5, CI: 1.1-1.9, P = 0.01), particularly if they were also hypochlorhydric (3.8, CI: 2.3-5.3 versus 1.9, CI: 1.3-2.5, P = 0.02). CONCLUSIONS In adults, H. pylori infection was associated with hypochlorhydria but had no detectable effect on occurrence of diarrhea. Among symptomatic subjects, H. pylori infection decreased severity of gastroenteritis.
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Hussey S, Jones NL. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2011:293-308.e10. [DOI: 10.1016/b978-1-4377-0774-8.10028-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Host-interactive genes in Amerindian Helicobacter pylori diverge from their Old World homologs and mediate inflammatory responses. J Bacteriol 2010; 192:3078-92. [PMID: 20400544 DOI: 10.1128/jb.00063-10] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori is the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults. H. pylori populations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of the cag-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparative H. pylori genomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing Amerindian H. pylori as a particularly close sister group to East Asian H. pylori. In contrast, phylogenetic analysis of the host-interactive genes vacA and cagA shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in the cag pathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225d cag architecture was fully functional via conserved elements, but the natural deletion of 13 cag pathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation.
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Deng XJ, Ma HS, Yu Q. Human-derived lactobacillus Lac15 inhibits Helicobacter pylori-induced p38 mitogen-activated protein kinase phosphorylation and interleukin-8 secretion in human gastric cancer SGC7901 cells. Shijie Huaren Xiaohua Zazhi 2009; 17:3096-3100. [DOI: 10.11569/wcjd.v17.i30.3096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of human-derived lactobacillus Lac15 on p38 mitogen-activated protein kinase (MAPK) phosphorylation and interleukin-8 (IL-8) secretion in human gastric cancer SGC7901 cells infected with Helicobacter pylori (H. pylori).
METHODS: SGC7901 cells were divided into four groups: normal control group, H. pylori infection group, SB203580 intervention group, and lactobacillus intervention group. The phosphorylation level of p38 MAPK in SGC7901 cells infected with H. pylori was evaluated by immunocytochemistry. The release of IL-8 in SGC7901 cells was detected by enzyme-linked immunosorbent assay (ELISA).
RESULTS: The phosphorylation level of p38 MAPK (IA: 1.90 ± 0.36 vs 14.01 ± 1.12, P < 0.01) and IL-8 secretion (27.2616 ± 0.27 ng/L vs 46.3691 ± 0.33 ng/L, P < 0.01) were significantly higher in SGC7901 cells infected with H. pylori than in normal control cells. After intervention with lactobacillus Lac15 at doses of 3×1011, 3×1010 and 3×109 cfu/L, both the phosphorylation level of p38 MAPK (IA: 4.61 ± 1.13, 6.11 ± 0.19 and 8.25 ± 0.56 vs 14.01 ± 1.12, respectively; all P < 0.01) and IL-8 secretion (42.3209 ± 0.24 ng/L, 42.1046 ± 0.23 ng/L and 43.4636 ± 0.25 ng/L vs 46.3691 ± 0.33 ng/L, respectively; all P < 0.05 or P < 0.01) decreased significantly in SGC7901 cells infected with H. pylori.
CONCLUSION: H. pylori infection can induce IL-8 secretion perhaps via a mechanism associated with promoting p38MAPK phosphorylation. Human-derived lactobacillus Lac15 can inhibit p38MAPK phosphorylation and thus decrease IL-8 secretion.
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Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology 2009; 136:1863-73. [PMID: 19457415 PMCID: PMC3644425 DOI: 10.1053/j.gastro.2009.01.073] [Citation(s) in RCA: 465] [Impact Index Per Article: 29.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2008] [Revised: 12/24/2008] [Accepted: 01/05/2009] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori is highly adapted for colonization of the human stomach and is present in about half of the human population. When present, H pylori is usually the numerically dominant gastric microorganism. H pylori typically does not cause any adverse effects, but it is associated with an increased risk of noncardia gastric adenocarcinoma, gastric lymphoma, and peptic ulcer. Disorders such as esophageal diseases and childhood-onset asthma were recently reported to occur more frequently in individuals who lack H pylori than in H pylori-positive persons. In this review, we discuss biologic factors that allow H pylori to colonize the human stomach, mechanisms by which H pylori increases the risk of peptic ulcer disease and noncardia gastric adenocarcinoma, and potential benefits that H pylori might confer to humans.
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Affiliation(s)
- Timothy L Cover
- Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37232, USA.
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Chiarini A, Calà C, Bonura C, Gullo A, Giuliana G, Peralta S, D'Arpa F, Giammanco A. Prevalence of virulence-associated genotypes of Helicobacter pylori and correlation with severity of gastric pathology in patients from western Sicily, Italy. Eur J Clin Microbiol Infect Dis 2008; 28:437-46. [PMID: 18958508 DOI: 10.1007/s10096-008-0644-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2008] [Accepted: 10/03/2008] [Indexed: 12/16/2022]
Abstract
In a bacterium like Helicobacter pylori, which is characterized by a recombinant population structure, the associated presence of genes encoding virulence factors might be considered an expression of a selective advantage conferred to strains with certain genotypes and, therefore, a potentially useful tool for predicting the clinical outcome of infections. However, differences in the geographical and ethnic prevalence of the H. pylori virulence-associated genotypes can affect their clinical predictive value and need to be considered in advance. In this study we carried out such an evaluation in a group of patients living in Sicily, the largest and most populous island in the Mediterranean Sea. cagA, vacA, babA2, hopQ, oipA, sabA, and hopZ were the H. pylori virulence-associated genes assayed; their presence, expression status or allelic homologs were detected in H. pylori DNA samples and/or isolated strains, obtained by gastric biopsy from 90 Sicilian patients with chronic gastritis, inactive (n = 37), active (n = 26), or active with peptic ulcer (n = 27). Genotypes cagA (+), vacAs1, vacAm1, babA2 (+), and hopQ I, I/II were identified in 51.8, 80.4, 35.2, 47.3, and 67.7% of the different samples respectively. Only these genotypes were associated with each other and with the active form of chronic gastritis, irrespective of the presence of a peptic ulcer. In our isolates their prevalence was more similar to values observed in the north of Italy and France than to those observed in Spain or other Mediterranean countries that are closer and climatically more similar to western Sicily.
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Affiliation(s)
- A Chiarini
- Department of Sciences for Health Promotion, University of Palermo, Italy.
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Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2007; 1:63-96. [PMID: 18039108 DOI: 10.1146/annurev.pathol.1.110304.100125] [Citation(s) in RCA: 408] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori is the main cause of peptic ulceration, distal gastric adenocarcinoma, and gastric lymphoma. Only 15% of those colonized develop disease, and pathogenesis depends upon strain virulence, host genetic susceptibility, and environmental cofactors. Virulence factors include the cag pathogenicity island, which induces proinflammatory, pro-proliferative epithelial cell signaling; the cytotoxin VacA, which causes epithelial damage; and an adhesin, BabA. Host genetic polymorphisms that lead to high-level pro-inflammatory cytokine release in response to infection increase cancer risk. Pathogenesis is dependent upon inflammation, a Th-1 acquired immune response and hormonal changes including hypergastrinaemia. Antral-predominant inflammation leads to increased acid production from the uninflamed corpus and predisposes to duodenal ulceration; corpus-predominant gastritis leads to hypochlorhydria and predisposes to gastric ulceration and adenocarcinoma. Falling prevalence of H. pylori in developed countries has led to a falling incidence of associated diseases. However, whether there are disadvantages of an H. pylori-free stomach, for example increased risk of esosphageal adenocarcinoma, remains unclear.
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Affiliation(s)
- John C Atherton
- Wolfson Digestive Diseases Centre and Institute of Infections, Immunity, and Inflammation, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
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Denno DM, Klein EJ, Young VB, Fox JG, Wang D, Tarr PI. Explaining unexplained diarrhea and associating risks and infections. Anim Health Res Rev 2007; 8:69-80. [PMID: 17692144 DOI: 10.1017/s1466252307001302] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Gastrointestinal illnesses are common afflictions. However, knowledge of their etiology is often lacking. Moreover, most cases of infections with reportable enteric pathogens (Campylobacter jejuni, Escherichia coli O157:H7, Salmonella, Shigella, Yersinia, Cryptosporidia and Giardia) have sporadic modes of acquisition, yet control measures are often biased towards mitigation of risks discerned by outbreak analysis. To determine the etiology of unexplained diarrhea it is important to study populations that can be matched to appropriate controls and to couple thorough classic microbiologic evaluation on receipt of specimens with archiving and outgrowth capabilities. Research evaluations should address the potential roles of a broad panel of candidate bacterial pathogens including diarrheagenic E. coli, Listeria monocytogenes, Helicobacters and jejuni Campylobacters, and also apply novel massively parallel sequencing and nucleic acid detection technologies that allow the detection of viral pathogens. To fill voids in our knowledge regarding sources of known enteric pathogens it will be critical to extend case-control studies to assess risk factors and exposures to patients with non-epidemic illnesses and to appropriate controls. By filling these gaps in our knowledge it should be possible to formulate rational prevention mechanisms for human gastrointestinal illnesses.
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Affiliation(s)
- Donna M Denno
- Department of Health Services, University of Washington School of Medicine, Seattle, WA, USA
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Windle HJ, Kelleher D, Crabtree JE. Childhood Helicobacter pylori infection and growth impairment in developing countries: a vicious cycle? Pediatrics 2007; 119:e754-9. [PMID: 17325213 DOI: 10.1542/peds.2006-2196] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We hypothesize that infection with the gastric pathogen Helicobacter pylori in children in developing countries is the initiator of a vicious cycle of events that result ultimately in malnutrition and growth impairment. Acute infection with H. pylori is accompanied by hypochlorhydria, which facilitates the acquisition of other enteropathogens because of removal of the gastric acid barrier, which then results in diarrheal disease and iron-deficiency anemia. This is likely to occur most frequently in developing regions where the prevalence of H. pylori infection is disproportionately high and multiple enteric coinfections are common. The consequent synergistic impact of diarrheal disease and micronutrient deficiency on growth and cognitive function in children has significant public health implications for socioeconomic development in these countries.
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Affiliation(s)
- Henry J Windle
- School of Medicine, Trinity College Dublin and Dublin Molecular Medicine Centre, Dublin, Ireland
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47
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VOLLAARD A, VERSPAGET H, ALI S, VISSER L, VEENENDAAL R, VAN ASTEN H, WIDJAJA S, SURJADI CH, VAN DISSEL J. Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia. Epidemiol Infect 2006; 134:163-70. [PMID: 16409664 PMCID: PMC2870371 DOI: 10.1017/s0950268805004875] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2005] [Indexed: 12/17/2022] Open
Abstract
We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.
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Affiliation(s)
- A. M. VOLLAARD
- Department of Infectious Diseases, Leiden University Medical Center, The Netherlands
| | - H. W. VERSPAGET
- Department of Gastroenterology–Hepatology, Leiden University Medical Center, The Netherlands
| | - S. ALI
- Department of Biology, Medical Faculty Atma Jaya Catholic University, Jakarta, Indonesia
| | - L. G. VISSER
- Department of Infectious Diseases, Leiden University Medical Center, The Netherlands
| | - R. A. VEENENDAAL
- Department of Gastroenterology–Hepatology, Leiden University Medical Center, The Netherlands
| | - H. A. G. H. VAN ASTEN
- Institute for International Health, Nijmegen University Medical Center, The Netherlands
| | - S. WIDJAJA
- Department of Internal Medicine, Medical Faculty Atma Jaya Catholic University, Jakarta, Indonesia
| | - CH. SURJADI
- Center for Health Research, Medical Faculty Atma Jaya Catholic University, Jakarta, Indonesia
| | - J. T. VAN DISSEL
- Department of Infectious Diseases, Leiden University Medical Center, The Netherlands
- Author for correspondence: J. T. van Dissel, M.D., Ph.D., Department of Infectious Diseases, C5-P, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. ()
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Ahmed N. 23 years of the discovery of Helicobacter pylori: is the debate over? Ann Clin Microbiol Antimicrob 2005; 4:17. [PMID: 16262889 PMCID: PMC1283743 DOI: 10.1186/1476-0711-4-17] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2005] [Accepted: 10/31/2005] [Indexed: 11/10/2022] Open
Abstract
The Gram negative curved bacillus H. pylori has become the prize bug of all times. Barry Marshall and Robin Warren the two discoverers of this organism have been awarded with this year's Nobel Prize. The Nobel committee at the Karolinska Institute of Sweden has selected this paradigm shift discovery of 1982 as the most impacting in medical sciences. This award has surprised many as the Nobel assembly has selected this 'Robert Koch styled medical detective work' for the prize as compared to many outstanding basic research stories on the waitlist. This editorial briefly touches the significant impact of H. pylori on gastroduodenal management and the path forward as the bug has become quite controversial in recent times.
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Affiliation(s)
- Niyaz Ahmed
- Pathogen Evolution Group and ISOGEM Collaborative Network on Genetics of Helicobacters (The International Society for Genomic and Evolutionary Microbiology), Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India
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49
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Abstract
The human gastrointestinal tract is colonized by an abundance of bacteria, which are in constant interaction with the epithelial lining usually leading to an intricate balance between tolerance and immunological response. There is ample evidence that the abundant presence of bacteria thus plays a role in the maintenance of human health, as well as in the induction of chronic inflammatory diseases of the gastrointestinal tract. Research in this field is, however, considerably hampered by the abundance of bacterial species, many of which have not even been characterized, and are difficult to culture specifically. These important limitations may to some extent be overcome by recent molecular biologic methods. Furthermore however, the adherent mucosal flora may differ largely from the luminal flora and that in excreta. These characteristics do not pertain to Helicobacter pylori, which generally colonizes the human stomach as a single strain with stable characteristics. Such colonization is stable throughout life, but can be treated. Furthermore, the association with chronic gastritis is very strong. For these reasons, H. pylori serves as an excellent model for the understanding of the processes involved in bacterial colonization and host response including mediation of immunoregulation, and the mechanisms by which this response can lead to disease.
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Affiliation(s)
- Ernst J Kuipers
- Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
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50
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Nizami SQ, Bhutta ZA, Weaver L, Preston T. Helicobacter pylori colonization in infants in a peri-urban community in Karachi, Pakistan. J Pediatr Gastroenterol Nutr 2005; 41:191-4. [PMID: 16056098 DOI: 10.1097/01.mpg.0000172263.12920.6b] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND The prevalence and incidence of Helicobacter pylori in children in Pakistan is not known. OBJECTIVES To measure the prevalence and age of acquisition of Helicobacter pylori infection/colonization in infants in a peri-urban community in Karachi, Pakistan. SETTING Field based epidemiologic study in a peri-urban community in Karachi, Pakistan. METHODS Infants aged 1 to 3 months were recruited from a birth cohort from the community. C-urea breath test (C-UBT) was performed on recruitment, and the test was repeated at 2, 3, 6, and 9 months of age. RESULTS One hundred forty-eight infants were recruited and had C-UBT on 319 occasions over a period of 2 years. Two hundred thirty-one=(72%) tests were positive: 80% (49/61) infants at 1 month of age, 79% (33/42) at 2 month of age, 76% (92/121) at 3 month of age, 58% (37/64) at 6 months of age, and 67% (20/30) at 9 months of age. CONCLUSIONS The study reveals an early colonization/infection of infants and a high prevalence of Helicobacter pylori in a peri-urban community in Karachi, Pakistan.
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