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Miao R, Chen J, Gao S, Wang L, Zhou W, Wan C, Wang Z. A randomised controlled clinical study of standard triple therapy, bismuth-based quadruple therapy and sequential therapy for Helicobacter pylori infection in children. BMC Pediatr 2024; 24:543. [PMID: 39180014 PMCID: PMC11342529 DOI: 10.1186/s12887-024-05020-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/19/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND AND AIM Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. METHODS A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. RESULTS In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. CONCLUSION The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.
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Affiliation(s)
- Ruixue Miao
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China
| | - Jing Chen
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China
| | - Shan Gao
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China
| | - Liyuan Wang
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China
| | - Wei Zhou
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China
- Clinical laboratory West China Second Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Chaomin Wan
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China.
| | - Zhiling Wang
- Department of Pediatrics, West China Second Hospital, Sichuan University, No 20, 3rd section of Renmin South Road, Chengdu, 610041, PR China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China.
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Dilaghi E, Felici E, Lahner E, Pilozzi E, Furio S, Lucchini L, Quatrale G, Piccirillo M, Parisi P, Curto S, Annibale B, Ferretti A, Mennini M, Persechino S, Di Nardo G. Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study. BMC Pediatr 2024; 24:417. [PMID: 38951792 PMCID: PMC11218114 DOI: 10.1186/s12887-024-04902-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 06/20/2024] [Indexed: 07/03/2024] Open
Abstract
BACKGROUND The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET). METHODS IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively. RESULTS 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached. CONCLUSION The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.
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Affiliation(s)
- Emanuele Dilaghi
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Enrico Felici
- Pediatric and Pediatric Emergency Unit, Children Hospital, AO SS Antonio E Biagio E C. Arrigo, Alessandria, Italy
| | - Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Emanuela Pilozzi
- Department of Clinical and Molecular Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Silvia Furio
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Livia Lucchini
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Giovanna Quatrale
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Marisa Piccirillo
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Pasquale Parisi
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Sara Curto
- Pediatric and Pediatric Emergency Unit, Children Hospital, AO SS Antonio E Biagio E C. Arrigo, Alessandria, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Alessandro Ferretti
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Maurizio Mennini
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Severino Persechino
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy
| | - Giovanni Di Nardo
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Via Grottarossa 1035, Rome, 00189, Italy.
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Kong G, Liu Z, Lu Y, Li M, Guo H. The association between Helicobacter pylori infection and inflammatory bowel disease in children: A systematic review with meta-analysis. Medicine (Baltimore) 2023; 102:e34882. [PMID: 37682136 PMCID: PMC10489354 DOI: 10.1097/md.0000000000034882] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 08/02/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Available literature has reported the association of Helicobacter pylori (H pylori) infection with inflammatory bowel disease (IBD) in adults. However, only a few studies have addressed the disease in children. AIM To ascertain the correlation of H pylori infection with IBD among children. METHODS The aim of this systematic review and meta-analysis is to assess the association between H pylori infection and IBD in children. We searched databases including Cochrane, EMBASE, Google Scholar, PubMed, Medline, and Web of Science to select relevant studies. Ultimately, based on predetermined inclusion criteria, we included 6 studies that met the requirements. Review Manager and Stata software were used to extract and analyze the data from the relevant studies. In the methods, we employed both qualitative and quantitative approaches for comprehensive analysis. Qualitative analysis involved describing study designs, sample characteristics, and results, while quantitative analysis involved statistical tests such as calculating pooled risk ratios and 95% confidence intervals to evaluate the association between H pylori infection and IBD in children. Lastly, by combining the results of the individual studies, our objective is to provide a comprehensive understanding of the relationship between H pylori infection and IBD in children. RESULTS In totality, we involved 2236 participants that were recruited in 6 studies. We detected no significant difference in H pylori prevalence (9.8% vs 12.7%, P = .12) by comparing the children IBD group to controls. Among the IBD children, we estimated odds ratio (OR) of H pylori infection to 0.62 [(95% confidence interval (CI) of 0.34-1.12)]. In children suffering from ulcerative colitis (UC) and Crohn disease (CD), the H pylori infection rates were higher than in those with IBD-unclassified (IBDU).When analyzed stratified by disease of study design, In CD group [OR = 1.42, 95% CI: 0.72-2.80)] (I2 = 0%, P = .64). but no significant difference in CD group. CONCLUSIONS No correlation was found between H pylori infection and the occurrence of IBD in children.
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Affiliation(s)
- Guiping Kong
- Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhifeng Liu
- Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yan Lu
- Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Mei Li
- Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hongmei Guo
- Department of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Ravikumara M. Helicobacter pylori in children: think before you kill the bug! Therap Adv Gastroenterol 2023; 16:17562848231177610. [PMID: 37361453 PMCID: PMC10285598 DOI: 10.1177/17562848231177610] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 05/06/2023] [Indexed: 06/28/2023] Open
Abstract
Since the discovery of Helicobacter pylori (H. pylori) as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that H. pylori gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world's population harbors H. pylori, these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of H. pylori against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with H. pylori-related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a "test and treat" strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of H. pylori, it is time to pause and think, are we causing more harm than good by eradicating H. pylori in every child who has this bug?
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Mizukami K, Sugano K, Takeshima T, Murakami K. Disease trends after Helicobacter pylori eradication based on Japanese nationwide claims and the health check-up database. World J Gastroenterol 2023; 29:692-705. [PMID: 36742170 PMCID: PMC9896615 DOI: 10.3748/wjg.v29.i4.692] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/28/2022] [Accepted: 01/09/2023] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is a risk factor for many diseases, including peptic ulcer disease and gastric cancer. While H. pylori eradication therapy can prevent these diseases, potentially unfavorable effects of eradication therapy have also been reported in some diseases, such as gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), inflammatory bowel disease (IBD), allergic diseases, and metabolic diseases. Consequently, both positive and negative impacts should be considered when assessing the effects of H. pylori eradication therapy.
AIM To compare the incidence of these diseases before and after H. pylori eradication and to comprehensively assess its effects.
METHODS This retrospective cohort study used a Japanese nationwide health claims database (April 2009-March 2020), developed by the Japanese Ministry of Health, Labour and Welfare. The database contained almost all health insurance claims data issued in Japan, and specific health check-up data for individuals who took the check-ups. Descriptive statistics were used for the analyses. Patients who received primary eradication therapy were defined as those prescribed medi-cation for H. pylori eradication. New diagnoses, defined as incidence of upper gastrointestinal diseases and IBD, and prevalence of allergic diseases were compared before and after eradication. The incidence and prevalence of each disease were also compared between the 3-year period before eradication (from the 4th to the 2nd year prior to the year of eradication) and the 3-year period after eradication (from the 1st to the 3rd year after the year of eradication) based on the age category and calendar year and month. Changes in body mass index and proportion of patients with metabolic syndrome (MS) were examined before and after eradication.
RESULTS We identified 5219731 patients who received primary eradication therapy. The 65-69 years age group had the greatest number of patients in both sexes. There was no significant increase in the incidence of GERD after eradication when considering the effects of aging and reporting period. However, the incidence of BE was higher in the 3-year period after eradication than in the 3-year period before eradication for all age categories (0.02%-0.10% vs < 0.01%-0.05%). The incidence of IBD and prevalence of allergic disease were also higher after eradication. In contrast, the incidence of gastric and duodenal ulcers and gastritis was reduced after eradication. In patients with at least one entry of health check-up data (1701111 patients), the percentage of patients with MS showed a slight increase following eradication (11.0% in the year of eradication and 12.2% after 5 years).
CONCLUSION The results suggest that H. pylori eradication therapy reduces peptic ulcers and gastritis; however, it is associated with increased incidence of several other chronic diseases.
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Affiliation(s)
- Kazuhiro Mizukami
- Department of Gastroenterology, Oita University, Oita 8795593, Japan
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi 3290498, Japan
| | | | - Kazunari Murakami
- Department of Gastroenterology, Oita University, Oita 8795593, Japan
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Treatment of Pediatric Helicobacter pylori Infection. Antibiotics (Basel) 2022; 11:antibiotics11060757. [PMID: 35740162 PMCID: PMC9219902 DOI: 10.3390/antibiotics11060757] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/29/2022] [Accepted: 05/29/2022] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori infection can cause gastritis, gastric or duodenal ulcers, mucosa-associated lymphoid tissue lymphoma, gastric cancer, and extra-gastrointestinal manifestations. Ideal treatment should be guided by antibiotic susceptibility testing. However, this is not feasible in many regions, so the treatment generally relies on clinical experience and regional culture sensitivity profiles. We aimed to integrate the treatment of pediatric H. pylori infection through a systematic literature review. Databases including PubMed, Cochrane Library, EMBASE, and Scholar were searched using terms containing (Helicobacter OR Helicobacter pylori OR H. pylori) AND (child OR pediatric) for all relevant manuscripts and guidelines, published from January 2011 to December 2021. The eradication rate for pediatric H. pylori infection was not satisfactory using triple therapy, sequential therapy, concomitant therapy, bismuth-based quadruple therapy, or adjuvant therapy with probiotics as the first-line therapy. Most therapies could not achieve the recommended eradication rate of >90%, which may be attributed to varying regional antibiotic resistance and possible poor children’s compliance. More studies are required to establish a best practice for pediatric H. pylori infection treatment.
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Are Inflammatory Bowel Disease and Colorectal Carcinoma Associated with Helicobacter pylori? A Prospective Study and Meta-analysis. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.1.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Observational studies regarding the correlation between colorectal carcinoma, inflammatory bowel disease and Helicobacter pylori infection are inconsistent. The present study aims to investigate the association between colorectal adenocarcinoma (CRA) and inflammatory bowel disease (IBD) with H. pylori status in 100 patients who have inflammatory bowel disease and colorectal carcinoma was confirmed disease by histological approach. Besides, a meta-analysis was performed of published studies, to evaluate the link between H. pylori infection and an increased risk of CRC and IBD. Among 67 cases with CRA and 33 cases with IBD, 59.7% and 51.5% were H. pylori positive; respectively. In the meta-analysis, thirty-nine articles were included, involving 13 231 cases with CRC and 2477 with IBD. The pooled odds ratio for CRC and IBD was 1.16 (95%CI = 0.73-1.82) and 0.42 (95%CI = 0.32-0.56); respectively. Our meta-analysis indicates that H. pylori is not associated with CRC.
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Zhou X, Liu X, He Q, Wang M, Lu H, You Y, Chen L, Cheng J, Li F, Fu X, Kwan HY, Zhou L, Zhao X. Ginger Extract Decreases Susceptibility to Dextran Sulfate Sodium-Induced Colitis in Mice Following Early Antibiotic Exposure. Front Med (Lausanne) 2022; 8:755969. [PMID: 35071260 PMCID: PMC8766511 DOI: 10.3389/fmed.2021.755969] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/23/2021] [Indexed: 12/04/2022] Open
Abstract
Background: Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years. Methods: A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels. Results: Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family Peptococcaceae and Helicobacter species to modulate microbiota structure and composition adversely affected by early antibiotic exposure. Conclusion: Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life.
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Affiliation(s)
- Xinghong Zhou
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Xiaoyu Liu
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Qiuxing He
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Ming Wang
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Hanqi Lu
- Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yanting You
- Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Liqian Chen
- Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Jingru Cheng
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Fei Li
- Department of Traditional Chinese Medicine, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - Xiuqiong Fu
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Hiu Yee Kwan
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Lin Zhou
- Department of Endocrinology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoshan Zhao
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China,Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, China,*Correspondence: Xiaoshan Zhao
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Kővári B, Pai RK. Upper Gastrointestinal Tract Involvement in Inflammatory Bowel Diseases: Histologic Clues and Pitfalls. Adv Anat Pathol 2022; 29:2-14. [PMID: 34310370 PMCID: PMC8663524 DOI: 10.1097/pap.0000000000000311] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The upper gastrointestinal (UGI) manifestations of inflammatory bowel diseases (IBDs) are frequently obscured by classic ileal and colonic symptoms and are reported to involve only 0.5% to 4% of adult patients. However, because of the improvement of endoscopic techniques and the growing use of esophagogastroduodenososcopy with biopsy, both asymptomatic and clinically significant esophageal, gastric, and duodenal manifestations are increasingly recognized. The UGI involvement in IBD was historically synonymous with Crohn's disease (CD), but the doctrine of ulcerative colitis (UC) being limited to the colon has been challenged, and UC-related gastroduodenal lesions have been reported. The diagnosis of UGI IBD should ideally rely on a combination of the clinical history, endoscopic picture, and histologic features. Although endoscopic changes such as aphthoid or longitudinal ulcers and bamboo-joint-like pattern are suggestive of CD, histologic evaluation increases the sensitivity of the IBD diagnosis since histologic alterations may be present in endoscopically unremarkable mucosa. Conversely, in many cases, the histologic findings are nonspecific, and the knowledge of clinical history is vital for reaching an accurate diagnosis. The presence of epithelioid granuloma is highly suggestive of CD but is present in a minority of CD cases; thus, pathologists should be aware of how to diagnose UGI IBD in the absence of granulomata. This article reviews the most important clinical, endoscopic, and histologic features of IBD-associated esophagitis, gastritis, and duodenitis, as well as the IBD-related manifestations in the biliary tract and the postcolectomy setting.
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Affiliation(s)
- Bence Kővári
- Department of Pathology, Henry Lee Moffitt Cancer Center and Research Institute, Tampa, FL
- Department of Pathology, University of Szeged and Albert Szent-Györgyi Health Center, Szeged, Hungary
| | - Rish K. Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ
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Homolak J, Nikolić M, Potoč D, Živković M, Bakula D, Budimir I, Pavić I, Hrabar D, Ljubičić N, Vražić D. The onset of ulcerative colitis upon Helicobacter pylori eradication in a 72-year-old woman: report of a rare case with a 3-year follow-up. BMC Gastroenterol 2021; 21:303. [PMID: 34332529 PMCID: PMC8325205 DOI: 10.1186/s12876-021-01876-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 07/06/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Epidemiological studies suggest an inverse association between H. pylori infection/exposure and inflammatory bowel disease prevalence/incidence, however, there are no reports of individual patients who developed a "non-transient" ulcerative colitis (UC) following H. pylori eradication. CASE PRESENTATION We report a case of a 72-year-old female with an elderly-onset UC developed upon H. pylori eradication and a 3-year follow-up of the progression to steroid-dependent colitis complicated with enteropathic arthritis and final containment of the disease with golimumab. In our patient, H. pylori eradication was associated with the development of pancolitis that evolved into clinically, endoscopically, and pathohistologically confirmed UC. CONCLUSIONS The case of our patient provides a unique clinical context for a growing body of literature suggesting molecular mechanisms involved in the interaction of genes, environment, and microbiota to be of critical importance in the etiopathogenesis of UC, and thus, provides a valuable set of complementary translational information for preclinical and epidemiological research on the topic.
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Affiliation(s)
- J Homolak
- Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - M Nikolić
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia. .,University of Zagreb School of Dental Medicine, Zagreb, Croatia.
| | - D Potoč
- University of Zagreb School of Dental Medicine, Zagreb, Croatia
| | - M Živković
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia
| | - D Bakula
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia
| | - I Budimir
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - I Pavić
- Department of Pathology, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia
| | - D Hrabar
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - N Ljubičić
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Dental Medicine, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - D Vražić
- Department of Periodontology, University of Zagreb School of Dental Medicine, Zagreb, Croatia
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11
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Shirzad-Aski H, Besharat S, Kienesberger S, Sohrabi A, Roshandel G, Amiriani T, Norouzi A, Keshtkar A. Association Between Helicobacter pylori Colonization and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2021; 55:380-392. [PMID: 32833699 DOI: 10.1097/mcg.0000000000001415] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 07/28/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Various observational studies have examined a potential relationship between Helicobacter pylori colonization and inflammatory bowel diseases (IBDs); however, results are inconclusive. This systematic review evaluates articles reporting an association between human H. pylori colonization and IBD. METHODS A systematic search of studies was conducted to evaluate a possible relationship between H. pylori colonization and IBD. Seven databases and different types of gray literature were searched. After screening for relevant articles, selection and data extraction were done. After that, the data were analyzed, and pooled odds ratios (ORs) were calculated, using meta-analysis. Heterogeneity, sensitivity, and subgroups analyses were conducted. Funnel plots followed by Begg and Egger tests were done to assess the publication bias. RESULTS Among 58 studies, including 13,549 patients with IBD and 506,554 controls, the prevalence of H. pylori colonization was 22.74% and 36.30%, respectively. A significant negative association was observed between H. pylori colonization and IBD (pooled OR: 0.45, 95% confidence interval 0.39-0.53, P≤0.001). The random-effect model showed significant statistical heterogeneity in the included studies (I2=79%). No publication bias was observed. Among subgroups, ORs were notably different when the data were stratified by the age difference between patient and control group, and by study regions and/or continent. Finally, the meta-regression analysis showed significant results, in terms of the age difference and region variables. CONCLUSIONS In this meta-analysis, all statistical data support the theory that H. pylori has a protective role in IBD. However, more primary studies using proper methodology are needed to confirm this association.
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Affiliation(s)
| | - Sima Besharat
- Infectious Diseases Research Center
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan
| | - Sabine Kienesberger
- Institute of Molecular Biosciences, University of Graz
- BioTechMed-Graz, Graz, Austria
| | - Ahmad Sohrabi
- Infectious Diseases Research Center
- Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan
| | - Taghi Amiriani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan
| | - Alireza Norouzi
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan
| | - Aabbas Keshtkar
- Department of Health Sciences Education Development, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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12
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Biernat MM, Bińkowska A, Łaczmański Ł, Biernat P, Krzyżek P, Gościniak G. Phenotypic and Genotypic Analysis of Resistant Helicobacter pylori Strains Isolated from Children with Gastrointestinal Diseases. Diagnostics (Basel) 2020; 10:E759. [PMID: 32992661 PMCID: PMC7601641 DOI: 10.3390/diagnostics10100759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 12/16/2022] Open
Abstract
Antibiotic resistance of Helicobacter pylori is currently a global issue. The aim of this study was to analyze actual antibiotic resistance rates of H. pylori strains isolated from children with primary infections and to compare the incidence of mutations that determine resistance to clarithromycin (CH) and metronidazole (MET) in children with different clinical diagnoses. A total of 91 H. pylori strains were isolated from 108 children with primary infections. Drug susceptibility testing of the strains was performed using E-test method. Classical sequencing of DNA fragments was used to detect point mutations for CH and MET resistance. Resistance to CH was detected in 31% of isolated strains (28/91), while resistance to MET and CH was detected in 35% (32/91) of strains. A2143G was the most frequently detected mutation and was dominant among strains isolated from children with peptic ulcer disease (80%). Mutations in the rdxA gene were found significantly more frequently among MET-resistant strains than MET-sensitive strains (p = 0.03, Chi2 = 4.3909). In children, a higher frequency of H. pylori multiresistant strains was observed compared with the previous study in the same area. Differences were found in the occurrence of point mutations among H. pylori strains resistant to CH isolated from children with different clinical diagnoses.
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Affiliation(s)
- Monika Maria Biernat
- Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, 50-367 Wroclaw, Poland;
| | - Aldona Bińkowska
- 2nd Military Field Hospital of the Polish Armed Forces, 50-984 Wroclaw, Poland;
| | - Łukasz Łaczmański
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;
| | - Paweł Biernat
- Department of Drugs Form Technology, Wroclaw Medical University, 50-556 Wroclaw, Poland;
| | - Paweł Krzyżek
- Department of Microbiology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Grażyna Gościniak
- Department of Microbiology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
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13
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Abstract
Although the features of lower gastrointestinal tract inflammation associated with ulcerative colitis and Crohn disease are generally familiar to pathologists, there is less awareness of and familiarity with the manifestations of inflammatory bowel disease in the esophagus, stomach, and duodenum. Nonetheless, their diagnosis has therapeutic and possibly prognostic implications, potentially foretelling severe complications. The recognition that ulcerative colitis can affect gastrointestinal organs proximal to the large intestine and terminal ileum represents a revision of concepts ingrained among generations of physicians. This article reviews the pathologic features and clinical significance of esophagitis, gastritis, and duodenitis associated with inflammatory bowel disease.
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Affiliation(s)
- Noam Harpaz
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA.
| | - Alexandros D Polydorides
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA
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14
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Boyanova L, Hadzhiyski P, Markovska R, Yaneva P, Yordanov D, Gergova G, Mitov I. Prevalence of Helicobacter pylori is still high among symptomatic Bulgarian children. Acta Microbiol Immunol Hung 2019; 66:255-260. [PMID: 30585499 DOI: 10.1556/030.65.2018.053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori positivity was assessed among 656 symptomatic children in 2010-2017. Overall infection prevalence was 24.5% and a significantly higher rate was detected in girls (28.5%) compared to boys (20.0%). Moreover, in children with duodenal ulcer, H. pylori prevalence was higher (47.4%) compared with the rest (23.9%). On the contrary, the infection was detected 1.9-fold less frequently in patients with GERD (14.5%) compared with the other (27.0%) patients and 2.1-fold less often in the presence of duodenogastric reflux (bile) reflux (13.0%) compared with the absence of the reflux (27.0%). No significant difference was observed between the younger (aged ≤7 years, 20.0%) and the older (aged 8-18 years, 25.5%) patients. H. pylori infection rate in Bulgarian pediatric patients between 2010 and 2017 was 2.5-fold lower than that in 1996-2006. In conclusion, H. pylori infection is still an important concern for Bulgarian children, although having decreased by about 1.8%/yearly over 21 years. This study reveals the importance of H. pylori diagnostics even in the youngest symptomatic children and demonstrates an inverse association between either GERD or bile reflux and H. pylori infection.
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Affiliation(s)
- Lyudmila Boyanova
- 1 Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
| | - Petyo Hadzhiyski
- 2 Specialized Hospital for Active Pediatric Treatment, Medical University of Sofia, Sofia, Bulgaria
| | - Rumyana Markovska
- 1 Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
| | - Penka Yaneva
- 2 Specialized Hospital for Active Pediatric Treatment, Medical University of Sofia, Sofia, Bulgaria
| | - Daniel Yordanov
- 1 Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
| | - Galina Gergova
- 1 Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
| | - Ivan Mitov
- 1 Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
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15
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Abstract
PURPOSE OF REVIEW Infections play a role in the pathogenesis of autoimmune diseases (AID). Several bacterial and viral pathogens play a double role, as both inducers and inhibitors of AID. In this review, we will present current evidence and discuss different aspects of this notion. RECENT FINDINGS Infectors that both inhibit and induce AID include Helicobacter pylori, Klebsiella pneumoniae, hepatitis B virus, group B Coxsackieviruses, Epstein-Barr virus and Lymphocytic choriomeningitis virus. Numerous AID are affected by infections, including polyarteritis nodosa, inflammatory bowel disease, and type 1 diabetes. Some pathogens, such as group B Coxsackieviruses, may induce and inhibit the development of the same AID. This reveals a complex role of infections in autoimmunity pathogenesis. SUMMARY Elucidating the exact role of each pathogen on each specific AID is important, as this will enable evaluating the manipulation of these infections in the treatment of AID.
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16
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Yu Y, Zhu S, Li P, Min L, Zhang S. Helicobacter pylori infection and inflammatory bowel disease: a crosstalk between upper and lower digestive tract. Cell Death Dis 2018; 9:961. [PMID: 30237392 PMCID: PMC6148320 DOI: 10.1038/s41419-018-0982-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 08/22/2018] [Accepted: 08/22/2018] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori has coexisted with humans for approximately 60,000 years and greater than 50% of the global population is infected with H. pylori. H. pylori was successfully cultured in vitro in 1983 and studies of H. pylori have achieved substantial advances over the last 35 years. Since then, H. pylori has been characterized as the primary pathogenic factor for chronic gastritis, peptic ulcer, and gastric malignancy. Numerous patients have received H. pylori eradication treatment, but only 1-2% of H. pylori-infected individuals ultimately develop gastric cancer. Recently, numerous epidemiological and basic experimental studies suggested a role for chronic H. pylori infection in protecting against inflammatory bowel disease (IBD) by inducing systematic immune tolerance and suppressing inflammatory responses. Here we summarize the current research progress on the association between H. pylori and IBD, and further describe the detailed molecular mechanism underlying H. pylori-induced dendritic cells (DCs) with the tolerogenic phenotype and immunosuppressive regulatory T cells (Tregs). Based on the potential protective role of H. pylori infection on IBD, we suggest that the interaction between H. pylori and the host is complicated, and H. pylori eradication treatment should be administered with caution, especially for children and young adults.
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Affiliation(s)
- Yang Yu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Li Min
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China.
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China.
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17
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Azimi T, Nasiri MJ, Chirani AS, Pouriran R, Dabiri H. The role of bacteria in the inflammatory bowel disease development: a narrative review. APMIS 2018; 126:275-283. [DOI: 10.1111/apm.12814] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 12/16/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Taher Azimi
- Department of Pathobiology; School of Public Health; Tehran University of Medical Sciences; Tehran Iran
| | - Mohammad Javad Nasiri
- Department of Medical Microbiology; School of Medicine; Shahid Beheshti University of Medical Sciences; Tehran Iran
| | - Alireza Salimi Chirani
- Department of Medical Microbiology; School of Medicine; Shahid Beheshti University of Medical Sciences; Tehran Iran
| | - Ramin Pouriran
- School of Medicine; Shahid Beheshti University of Medical Sciences; Tehran Iran
| | - Hossein Dabiri
- Department of Medical Microbiology; School of Medicine; Shahid Beheshti University of Medical Sciences; Tehran Iran
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18
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Zabala Torrres B, Lucero Y, Lagomarcino AJ, Orellana-Manzano A, George S, Torres JP, O'Ryan M. Review: Prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter 2017. [PMID: 28643393 DOI: 10.1111/hel.12399] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Long-term persistent Helicobacter pylori infection has been associated with ulceropeptic disease and gastric cancer. Although H. pylori is predominantly acquired early in life, a clear understanding of infection dynamics during childhood has been obfuscated by the diversity of populations evaluated, study designs, and methods used. AIM Update understanding of true prevalence of H. pylori infection during childhood, based on a critical analysis of the literature published in the past 5 years. METHODS Comprehensive review and meta-analysis of original studies published from 2011 to 2016. RESULTS A MEDLINE® /PubMed® search on May 1, 2016, using the terms pylori and children, and subsequent exclusion, based on abstract review using predefined criteria, resulted in 261 citations. An Embase® search with the same criteria added an additional 8 citations. In healthy children, meta-analysis estimated an overall seroprevalence rate of 33% (95% CI: 27%-38%). Seven healthy cohort studies using noninvasive direct detection methods showed infection prevalence estimates ranging from 20% to 50% in children ≤5 and 38% to 79% in children >5 years. The probability of infection persistence after a first positive sample ranged from 49% to 95%. Model estimates of cross-sectional direct detection studies in asymptomatic children indicated a prevalence of 37% (95% CI: 30%-44%). Seroprevalence, but not direct detection rates increased with age; both decreased with increasing income. The model estimate based on cross-sectional studies in symptomatic children was 39% (95% CI: 35%-43%). CONCLUSIONS The prevalence of H. pylori infection varied widely in the studies included here; nevertheless, model estimates by detection type were similar, suggesting that overall, one-third of children worldwide are or have been infected. The few cohort and longitudinal studies available show variability, but most studies, show infection rates over 30%. Rather surprisingly, overall infection prevalence in symptomatic children was only slightly higher, around 40%. Studies including only one positive stool sample should be interpreted with caution as spontaneous clearance can occur.
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Affiliation(s)
- Beatriz Zabala Torrres
- Microbiology and Mycology Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile.,Universidad de Aysén, Campus Rio Simpson, Coyhaique, Chile
| | - Yalda Lucero
- Department of Pediatrics, Faculty of Medicine, Hospital Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile
| | - Anne J Lagomarcino
- Microbiology and Mycology Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Andrea Orellana-Manzano
- Escuela Superior Politécnica del Litoral, ESPOL, Facultad de Ciencias de la Vida (FCV), Campus Gustavo Galindo Km. 30.5 Vía Perímetral, P. O. Box 09-01-5863, Guayaquil, Ecuador
| | - Sergio George
- Microbiology and Mycology Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Juan P Torres
- Department of Pediatrics, Faculty of Medicine, Hospital Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile
| | - Miguel O'Ryan
- Microbiology and Mycology Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
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19
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Castaño-Rodríguez N, Kaakoush NO, Lee WS, Mitchell HM. Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis. Gut 2017; 66:235-249. [PMID: 26508508 DOI: 10.1136/gutjnl-2015-310545] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 10/03/2015] [Accepted: 10/05/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed. DESIGN Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. RESULTS Analyses comprising patients with Crohn's disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric H. pylori infection and IBD (P-OR: 0.43, p value <1e-10). This association appears to be stronger in patients with CD (P-OR: 0.38, p value <1e-10) and IBDU (P-OR: 0.43, p value=0.008) than UC (P-OR: 0.53, p value <1e-10). Stratification by age, ethnicity and medications showed significant results. In contrast to gastric H. pylori, non H. pylori-EHS (P-OR: 2.62, p value=0.001) and Campylobacter spp, in particular C. concisus (P-OR: 3.76, p value=0.006) and C. showae (P-OR: 2.39, p value=0.027), increase IBD risk. CONCLUSIONS H. pylori infection is negatively associated with IBD regardless of ethnicity, age, H. pylori detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and Campylobacter spp increase the risk of IBD. These results infer that H. pylori might exert an immunomodulatory effect in IBD.
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Affiliation(s)
- Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
| | - Nadeem O Kaakoush
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
| | - Way Seah Lee
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur, Malaysia.,University Malaya Pediatrics and Child Health Research Group, University Malaya, Kuala Lumpur, Malaysia
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
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20
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Semper RP, Gerhard M. The Lost Friend: H. pylori. BIRKHÄUSER ADVANCES IN INFECTIOUS DISEASES 2017:69-97. [DOI: 10.1007/978-3-319-69968-4_5] [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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22
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Arnold IC, Müller A. Helicobacter pylori: Does Gastritis Prevent Colitis? Inflamm Intest Dis 2016; 1:102-112. [PMID: 29922665 DOI: 10.1159/000445985] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 04/05/2016] [Indexed: 12/15/2022] Open
Abstract
Background Since its discovery in the early 1980s, Helicobacter pylori has been linked to a variety of gastric and extragastric diseases. Chronic infection with H. pylori causes histologically evident gastritis in all colonized individuals and is the predominant risk factor for gastric and duodenal ulcers as well as gastric adenocarcinoma. However, increasingly robust experimental and epidemiological evidence suggests that H. pylori may at the same time be beneficial to its carriers, as it efficiently prevents allergic disorders and chronic inflammatory conditions. The purpose of this review is to summarize and document the latest evidence for a possible inverse association of H. pylori infection status and the risk of inflammatory bowel disease (IBD), as provided in both experimental and human observational studies. The pathogenesis of IBDs, the available mouse models for these diseases and the dual role of H. pylori in health and disease are presented in dedicated chapters. Summary and Key Messages Almost all available epidemiological data suggest that H. pylori infection is inversely associated with both Crohn's disease (CD) and ulcerative colitis in European, Asian as well as American populations; large meta-analyses reviewing 30 original articles or more document that this inverse association is especially strong in CD patients and in children and young adults. Experimental data available from various mouse models of IBD confirm that live H. pylori infection as well as treatment with immunomodulatory molecules of H. pylori reduce clinical and histopathological IBD symptoms. Various proposed mechanisms involving the tolerization of dendritic cells, the production of protective cytokines and the preferential induction and differentiation of regulatory T-cells are presented. The implications of the beneficial aspects of the Helicobacter-host interaction for H. pylori eradication decisions, as well as potential new therapeutic options in the treatment of IBD are discussed in this review.
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Affiliation(s)
- Isabelle C Arnold
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
| | - Anne Müller
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
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23
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Cheng C, Li CP. Influence of Helicobacter pylori infection on extra-gastric diseases. Shijie Huaren Xiaohua Zazhi 2016; 24:2010-2018. [DOI: 10.11569/wcjd.v24.i13.2010] [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
The discovery of Helicobacter pylori (H. pylori) colonization of the stomach and its pathogenic effects is a crucial landmark in modern gastroenterology. There have been many studies reporting that the natural history of many disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma are linked with the presence of this bacterium. Moreover, H. pylori is often involved in the pathogenic processes of a variety of extra-gastric diseases, especially those characterized by persistent and low grade systemic inflammation. The proposed mechanisms ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This paper will review the results of the most important studies on the association of H. pylori infection with extra-gastric diseases, such as autoimmune, neoplastic, cardiovascular and other related disorders, as well as possible mechanisms implicated in the pathogenesis of these extra-gastric diseases.
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24
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Bartels LE, Jepsen P, Christensen LA, Gerdes LU, Vilstrup H, Dahlerup JF. Diagnosis of Helicobacter Pylori Infection is Associated with Lower Prevalence and Subsequent Incidence of Crohn's Disease. J Crohns Colitis 2016; 10:443-8. [PMID: 26674958 PMCID: PMC4946761 DOI: 10.1093/ecco-jcc/jjv229] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 12/04/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Helicobacter pylori infection may protect against some chronic inflammatory diseases. This study examined H. pylori infection and its association with the prevalence of the gastrointestinal diseases Crohn's disease [CD], ulcerative colitis [UC], and coeliac disease [CeD]. Incident cases in a follow-up period after H. pylori testing were recorded to investigate if protective effects of H. pylori persisted after probable eradication. METHODS This was a historical cohort study performed in the Central Denmark Region. Patients were enrolled consecutively from primary health care centres after a urea breath test [UBT] for H. pylori and were then followed for a median of 6 years. The patient's diseases, country of birth, and gender were acquired from nationwide administrative registries. We used logistic regression to compare the prevalences of CD, UC, and CeD and Cox regression to compare the incidences of CD, UC, and CeD between H. pylori-positive and H. pylori-negative patients, adjusting for confounding variables. RESULTS We found a lower prevalence of CD in H. pylori-positive than in H. pylori-negative patients (odds ratio = 0.36 [0.17-0.75]). There were fewer incident cases of CD in H. pylori-positive than H. pylori-negative patients in the follow-up period (hazard ratio = 0.59 [0.36-0.96]). Similar trends were found for CeD but not for UC. CONCLUSIONS H. pylori infection may be a protective factor against the development of CD. However, the incidence of CD is still reduced after UBT and probable H. pylori eradication; thus, H. pylori status may be a marker for other factors that protect against CD.
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Affiliation(s)
- Lars E. Bartels
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Lisbet A. Christensen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Lars U. Gerdes
- Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens F. Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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25
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Jiminez JA, Uwiera TC, Douglas Inglis G, Uwiera RRE. Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathog 2015; 7:29. [PMID: 26561503 PMCID: PMC4641401 DOI: 10.1186/s13099-015-0076-y] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 10/22/2015] [Indexed: 02/06/2023] Open
Abstract
Acute and chronic inflammatory diseases of the intestine impart a significant and negative impact on the health and well-being of human and non-human mammalian animals. Understanding the underlying mechanisms of inflammatory disease is mandatory to develop effective treatment and prevention strategies. As inflammatory disease etiologies are multifactorial, the use of appropriate animal models and associated metrics of disease are essential. In this regard, animal models used alone or in combination to study acute and chronic inflammatory disease of the mammalian intestine paired with commonly used inflammation-inducing agents are reviewed. This includes both chemical and biological incitants of inflammation, and both non-mammalian (i.e. nematodes, insects, and fish) and mammalian (i.e. rodents, rabbits, pigs, ruminants, dogs, and non-human primates) models of intestinal inflammation including germ-free, gnotobiotic, as well as surgical, and genetically modified animals. Importantly, chemical and biological incitants induce inflammation via a multitude of mechanisms, and intestinal inflammation and injury can vary greatly according to the incitant and animal model used, allowing studies to ascertain both long-term and short-term effects of inflammation. Thus, researchers and clinicians should be aware of the relative strengths and limitations of the various animal models used to study acute and chronic inflammatory diseases of the mammalian intestine, and the scope and relevance of outcomes achievable based on this knowledge. The ability to induce inflammation to mimic common human diseases is an important factor of a successful animal model, however other mechanisms of disease such as the amount of infective agent to induce disease, invasion mechanisms, and the effect various physiologic changes can have on inducing damage are also important features. In many cases, the use of multiple animal models in combination with both chemical and biological incitants is necessary to answer the specific question being addressed regarding intestinal disease. Some incitants can induce acute responses in certain animal models while others can be used to induce chronic responses; this review aims to illustrate the strengths and weaknesses in each animal model and to guide the choice of an appropriate acute or chronic incitant to facilitate intestinal disease.
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Affiliation(s)
- Janelle A. Jiminez
- />Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB Canada
- />Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB Canada
| | - Trina C. Uwiera
- />Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB Canada
| | - G. Douglas Inglis
- />Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB Canada
| | - Richard R. E. Uwiera
- />Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB Canada
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Abstract
This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.
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Affiliation(s)
- Eleftheria Roma
- First Department of Pediatrics, University of Athens, Athens, Greece
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
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Franceschi F, Gasbarrini A, Polyzos SA, Kountouras J. Extragastric Diseases and Helicobacter pylori. Helicobacter 2015; 20 Suppl 1:40-6. [PMID: 26372824 DOI: 10.1111/hel.12256] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The extragastric manifestations of Helicobacter pylori infection still remain a very strong topic throughout the H. pylori world. Indeed, H. pylori may interfere with many biological processes, both inside and outside of the stomach, possibly influencing or determining the occurrence of many diseases outside of the stomach. While its role in idiopathic thrombocytopenic purpura and sideropenic anemia has already been recognized, emerging evidence suggests that H. pylori may increase the risk of acute coronary syndrome, contribute to insulin resistance and be associated with neurodegenerative, respiratory, and other miscellaneous disorders previously associated with other conditions. Different pathogenic mechanisms have been hypothesized, including the induction of a low-grade inflammatory state and the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic in the last year.
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Affiliation(s)
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Catholic University of Rome, Rome, Italy
| | - Stergios A Polyzos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Macedonia, Greece
| | - Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Macedonia, Greece
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