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Wang Q, Ma S, Liu M, Tao Y, Sun Z. Gut microbiota, inflammatory cytokines and gastro-esophageal reflux disease: A Mendelian randomization analysis. Medicine (Baltimore) 2025; 104:e41386. [PMID: 39889191 PMCID: PMC11789916 DOI: 10.1097/md.0000000000041386] [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: 08/16/2024] [Revised: 01/08/2025] [Accepted: 01/10/2025] [Indexed: 02/02/2025] Open
Abstract
Gut microbiota has been recognized as an extrahepatic manifestation of gastro-esophageal reflux disease (GERD) in observational studies. However, the directionality and causality of the association and whether cytokines act as a mediator remain unclear. We aim to estimate the casual relationship between gut microbiota, inflammatory cytokines and GERD using a 2-sample Mendelian randomization method. Gut microbiota, cytokines, and GERD were identified using summary data from the genome-wide association studies and the FinnGen consortium. The primary method for causal estimation was the inverse-variance weighted approach, complemented by a range of sensitivity analyses aimed at assessing heterogeneity, horizontal pleiotropy, and the robustness of the findings. Furthermore, mediation analysis was conducted to evaluate the association between gut microbiota and GERD, with 5 cytokines, and to calculate the mediated proportions. We found 3 positive and 3 negative causal associations observed between genetic predisposition in gut microbiota and GERD. Additionally, 2 positive and 3 negative causal associations were identified between cytokines and GERD. Our analysis unveiled that TNF-related apoptosis-inducing ligand levels (TRAIL) mediated the causal relationships between the genera Family XIII UCG001 and Senegalimassilia, and GERD. We identified causal effects between 6 bacterial traits, 5 inflammatory cytokines, and GERD. Notably, we furnished causal evidence linking TRAIL levels to a substantial proportion of the risk attributed to genus Family XIII UCG001 and genus Senegalimassilia, thereby mediating the risk of GERD. These findings offer novel avenues for therapeutic interventions targeting individuals with GERD.
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Affiliation(s)
- Qilin Wang
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Shenghui Ma
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Mengjie Liu
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Yu Tao
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Zhiguang Sun
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
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2
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Liu J, Liu YL. Should we pay more attention to the potential link between Helicobacter pylori and esophageal cancer in Asian countries. World J Gastroenterol 2024; 30:4958-4963. [PMID: 39679315 PMCID: PMC11612706 DOI: 10.3748/wjg.v30.i46.4958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 10/25/2024] [Accepted: 11/01/2024] [Indexed: 11/21/2024] Open
Abstract
The presence of Helicobacter pylori (H. pylori) infection has been indicated to have a protective influence on esophageal cancer (EC) in some studies, but its specific impact on the risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma remains inconclusive. This manuscript comment addresses the recent study by López-Gómez et al. Despite it was a retrospective observational study without a control group, this study revealed a notably low prevalence of H. pylori infection among EC patients, indicating a potential association between H. pylori and EC in Spain. It is important to note that the relationship between H. pylori and the risk of EC varies geographically. We also conducted a meta-analysis focusing on this association in Asian populations to offer precise clinical insights. However, no significant correlation between H. pylori infection and EC was identified, suggesting that the perceived protective effect of H. pylori against EC may have been overestimated in the Asian population.
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Affiliation(s)
- Jie Liu
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ying-Ling Liu
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, Anhui Province, China
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Liu X, Li B, Liang L, Han J, Mai S, Liu L. From microbes to medicine: harnessing the power of the microbiome in esophageal cancer. Front Immunol 2024; 15:1450927. [PMID: 39600698 PMCID: PMC11588724 DOI: 10.3389/fimmu.2024.1450927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024] Open
Abstract
Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.
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Affiliation(s)
- Xiaoyan Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Bang Li
- Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Liping Liang
- Department of Gastroenterology and Hepatology, Guangzhou Key Laboratory of Digestive Diseases, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jimin Han
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Shijie Mai
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Le Liu
- Integrated Clinical Microecology Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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Chen H, Ren C. Helicobacter pylori Eradication Treatment Might Help Reduce the Risk of Esophageal Adenocarcinoma. Gastroenterology 2024:S0016-5085(24)05477-5. [PMID: 39306253 DOI: 10.1053/j.gastro.2024.08.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 08/13/2024] [Indexed: 10/09/2024]
Affiliation(s)
- Hui Chen
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Chuanli Ren
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
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López-Gómez M, Morales M, Fuerte R, Muñoz M, Delgado-López PD, Gómez-Cerezo JF, Casado E. Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma. World J Gastroenterol 2024; 30:3479-3487. [PMID: 39156503 PMCID: PMC11326089 DOI: 10.3748/wjg.v30.i29.3479] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/24/2024] [Accepted: 07/11/2024] [Indexed: 07/29/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial. AIM To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital. METHODS We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded. RESULTS A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant (n = 47, 52.8%), followed by squamous cell carcinoma (n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment. CONCLUSION In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.
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Affiliation(s)
- Miriam López-Gómez
- Department of Medical Oncology, Precision Oncology Laboratory, Infanta Sofía University Hospital, San Sebastián de los Reyes 28231, Madrid, Spain
| | - Maria Morales
- Department of Medical Oncology, Infanta Sofía University Hospital, San Sebastián de los Reyes 28702, Spain
| | - Rebeca Fuerte
- Department of Internal Medicine, Infanta Sofía University Hospital, San Sebastián de los Reyes 28703, Madrid, Spain
| | - Marta Muñoz
- Department of Pathology, Infanta Sofía University Hospital, San Sebastián de los Reyes 28702, Spain
| | | | - Jorge Francisco Gómez-Cerezo
- Department of Internal Medicine, Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and Innovation, San Sebastian de los Reyes 28702, Madrid, Spain
| | - Enrique Casado
- Department of Medical Oncology, Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and Innovation, San Sebastian de los Reyes 28702, Madrid, Spain
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Wang G. Advancement of the relationship between esophageal microorganisms and esophageal diseases. GASTROENTEROLOGY & ENDOSCOPY 2024; 2:112-116. [DOI: 10.1016/j.gande.2024.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Qin H, Suo S, Yang F, Hao P, Zhang X. The role of digestive system diseases in cerebrovascular disease: a comprehensive Mendelian randomization study. Front Neurol 2024; 15:1389352. [PMID: 38854966 PMCID: PMC11157012 DOI: 10.3389/fneur.2024.1389352] [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: 02/22/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024] Open
Abstract
Background Cerebrovascular disease, among the most prevalent neurological disorders, poses a substantial threat to human health with its elevated mortality and disability rates, placing considerable strain on healthcare systems. Although several studies in recent years have suggested a potential association between digestive system diseases and cerebrovascular diseases, the findings remain inconsistent. Methods Genome-wide association study (GWAS) summary data for 12 digestive diseases and cerebrovascular diseases were used to conduct Mendelian randomization (MR) analysis. In this investigation, we endeavored to elucidate the causal relationship between digestive system diseases and cerebrovascular diseases. Employing a comprehensive approach, including two-sample MR (TSMR), multivariate MR (MVMR), and two-step MR analysis, we leveraged summary statistics data obtained from published GWAS. The primary analysis method employed was inverse variance weighted (IVW), with MR-Egger and weighted median (WM) as secondary methods. Sensitivity analysis included heterogeneity testing, horizontal multivariate testing, MR-PRESSO, and a "leave-one-out" method. Additionally, the F-statistic was utilized to assess the strength of instrumental variables, ensuring robust results. Results In the TSMR analysis, this study found a significant causal relationship between genetically predicted gastroesophageal reflux disease (GERD) and any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), intracranial aneurysm (IA), and subarachnoid hemorrhage (SAH). In MVMR analysis, this study found that even after adjusting for systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes (T2D), the causal relationship remains exist. In the two-step MR mediation analysis, it was found that BMI, SBP and T2D play mediating role in the causal relationship between GERD and cerebrovascular diseases. Conclusion This study indicates a clear positive causal relationship between GERD and cerebrovascular diseases, and this causal association remains significant even after adjusting for BMI, SBP and T2D. The mediation MR analysis suggests that BMI, SBP and T2D may mediate the causal relationship between GERD and the risk of cerebrovascular diseases.
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Affiliation(s)
- Hao Qin
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
| | - Shihuan Suo
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
| | - Fan Yang
- Department of Anesthesiology, The First Hospital of Jilin University, Changchun, China
| | - Pengfei Hao
- Department of Neurosurgery, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Xianfeng Zhang
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
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Leech T, Peiris M. Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis. J Gastroenterol 2024; 59:165-178. [PMID: 38221552 PMCID: PMC10904498 DOI: 10.1007/s00535-023-02065-9] [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: 08/24/2023] [Accepted: 11/30/2023] [Indexed: 01/16/2024]
Abstract
Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD is proton pump inhibitors (PPIs), however, PPIs are ineffective in a large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number and location are likely to play interrelated roles in nociception in the oesophagus of GORD patients. Simultaneously, alterations in cells of the oesophageal mucosa, namely epithelial cells, mast cells, dendritic cells, and T lymphocytes, have been a focus of GORD research for several years. The oesophagus of GORD patients exhibits both macro- and micro-inflammation as a response to chronic acidic reflux at the epithelium. In other conditions of the GI tract, such as IBS and IBD, well-characterised bidirectional processes between immune cells and mucosal nerve fibres contribute to pathogenesis and symptom generation. Sensory alterations in these conditions such as nerve fibre outgrowth and hypersensitivity can be driven by inflammatory processes, which promote visceral pain signalling. This review will examine what is currently known of the molecular pathways linking inflammation and sensory perception leading to the development of GORD symptoms and explore potentially relevant mechanisms in other GI regions which may indicate new areas in GORD research.
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Affiliation(s)
- Tom Leech
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK
| | - Madusha Peiris
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
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Wang K, Wang S, Chen Y, Lu X, Wang D, Zhang Y, Pan W, Zhou C, Zou D. Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study. Front Immunol 2024; 15:1327503. [PMID: 38449873 PMCID: PMC10914956 DOI: 10.3389/fimmu.2024.1327503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/05/2024] [Indexed: 03/08/2024] Open
Abstract
Background Numerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, a clear causative association between the gut microbiota and GERD has yet to be definitively ascertained, given the presence of confounding variables. Methods The genome-wide association study (GWAS) pertaining to the microbiome, conducted by the MiBioGen consortium and comprising 18,340 samples from 24 population-based cohorts, served as the exposure dataset. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. The inverse variance-weighted (IVW) method was performed as a primary analysis, the other four methods were used as supporting analyses. Furthermore, sensitivity analyses encompassing Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and leave-one-out methodology were carried out to identify potential heterogeneity and horizontal pleiotropy. Ultimately, a reverse MR assessment was conducted to investigate the potential for reverse causation. Results The IVW method's findings suggested protective roles against GERD for the Family Clostridiales Vadin BB60 group (P = 0.027), Genus Lachnospiraceae UCG004 (P = 0.026), Genus Methanobrevibacter (P = 0.026), and Phylum Actinobacteria (P = 0.019). In contrast, Class Mollicutes (P = 0.037), Genus Anaerostipes (P = 0.049), and Phylum Tenericutes (P = 0.024) emerged as potential GERD risk factors. In assessing reverse causation with GERD as the exposure and gut microbiota as the outcome, the findings indicate that GERD leads to dysbiosis in 13 distinct gut microbiota classes. The MR results' reliability was confirmed by thorough assessments of heterogeneity and pleiotropy. Conclusions For the first time, the MR analysis indicates a genetic link between gut microbiota abundance changes and GERD risk. This not only substantiates the potential of intestinal microecological therapy for GERD, but also establishes a basis for advanced research into the role of intestinal microbiota in the etiology of GERD.
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Affiliation(s)
- Kui Wang
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Gastroenterology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Suijian Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Stantou University Medical College, Stantou, China
| | - Yuhua Chen
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Xinchen Lu
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Danshu Wang
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yao Zhang
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei Pan
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Chunhua Zhou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Jung DH, Youn YH, Kim DH, Lim CH, Lim HS, Moon HS, Lee JY, Park H, Hong SJ. Esophageal Microbiota and Nutritional Intakes in Patients With Achalasia Before and After Peroral Endoscopic Myotomy. J Neurogastroenterol Motil 2022; 28:237-246. [PMID: 35362450 PMCID: PMC8978113 DOI: 10.5056/jnm21057] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/22/2021] [Accepted: 08/10/2021] [Indexed: 12/18/2022] Open
Abstract
Background/Aims The composition of the microbiota in the esophagus is only partially understood, especially in patients with achalasia. We aim to investigate the esophageal microbial community and nutritional intakes in patients with achalasia before and after peroral endoscopic myotomies (POEM). Methods Twenty-nine patients were prospectively enrolled from 4 referral institutions across Korea. We collected esophageal samples (mucosal biopsies and retention fluid) and conducted dietary surveys for nutritional intake before and 8 weeks after POEM. The esophageal microbiota was analyzed by 16S rRNA gene sequencing targeting the V3-V4 region. Results Out of the 105 samples from 29 patients, 99 samples were subjected to microbial bioinformatic analysis after quality control, which excluded samples with no amplification or low-quality sequence data. The overall esophageal microbial compositions of patients with achalasia showed that Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria were the dominant phyla, representing over 95% of the total phyla in all groups. At the genus level, Streptococcus was the most abundant in all groups. The observed operational taxonomic unit number was significantly higher in the retention fluid than in the tissue biopsies. However, the esophageal microbial composition showed no significant changes 8 weeks post POEM. The dietary survey analysis showed that nutritional intake significantly improved post POEM. Conclusion This study determined the unique esophageal microbial composition of patients with achalasia, and also found that the microbial composition did not significantly change after POEM in the short-term, despite a significant improvement in the nutritional intake.
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Affiliation(s)
- Da Hyun Jung
- Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Hoon Youn
- Department of Gastroenterology, Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee-Sook Lim
- Department of Food and Nutrition, Yeonsung University, Anyang, Gyeonggi-do, Korea.,Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Korea (Current address)
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyojin Park
- Department of Gastroenterology, Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Gyeonggi-do, Korea
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The oesophageal microbiome and cancer: hope or hype? Trends Microbiol 2021; 30:322-329. [PMID: 34493428 DOI: 10.1016/j.tim.2021.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 08/12/2021] [Accepted: 08/16/2021] [Indexed: 02/08/2023]
Abstract
The human oesophagus is home to a complex microbial community, the oesophageal microbiome. Despite decades of work, we still have only a poor, low-resolution view of this community, which makes it hard to distinguish hope from hype when it comes to assessing links between the oesophageal microbiome and cancer. Here we review the potential importance of this microbiome and discuss new approaches, including culturomics, metagenomics, and recovery of whole-genome sequences, that bring renewed hope for an in-depth characterisation of this community that could deliver translational impact.
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Zhang Z, Curran G, Altinok Dindar D, Wu Y, Wu H, Sharpton T, Zhao L, Lieberman D, Otaki F. Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review. Clin Transl Gastroenterol 2021; 12:e00390. [PMID: 34446641 PMCID: PMC8397287 DOI: 10.14309/ctg.0000000000000390] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 07/09/2021] [Indexed: 11/29/2022] Open
Abstract
Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent-not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.
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Affiliation(s)
- Zhenzhen Zhang
- Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Grace Curran
- Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Duygu Altinok Dindar
- Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Ying Wu
- Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, Oregon, USA
| | - Hui Wu
- Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, Oregon, USA
| | - Thomas Sharpton
- Department of Microbiology, Oregon State University, Corvallis, Oregon, USA
- Department of Statistics, Oregon State University, Corvallis, Oregon, USA
| | - Lianmei Zhao
- Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China;
| | - David Lieberman
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Oregon Health Sciences University, Portland, Oregon, USA
| | - Fouad Otaki
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Oregon Health Sciences University, Portland, Oregon, USA
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Grover K, Gregory S, Gibbs JF, Emenaker NJ. A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach. J Gastrointest Oncol 2021; 12:S290-S300. [PMID: 34422393 DOI: 10.21037/jgo-2019-gi-07] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 06/10/2020] [Indexed: 12/27/2022] Open
Abstract
The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions. Dysregulation of these interactions, or dysbiosis of the gastrointestinal tract, has been implicated in a growing list of pathologies including nonalcoholic fatty liver disease, cardiovascular disease, obesity, diabetes, depression, Parkinson's disease, autism, and various gastrointestinal cancers. Gastric and esophageal cancer, for example, continue to remain as two of the most common causes of cancer-related deaths worldwide, therefore there is an increased emphasis on investigating the role of dysbiosis on these cancers. In this review, we discuss the development and structure of the gut microbiome, its homeostatic and dysbiotic mechanisms, and the key microbes in esophageal and gastric carcinogenesis with a focus on bacterial biology. Further clarification of these pathways and discovery of diagnostic or therapeutic targets could have broad impacts on global subpopulations. It is important to understand the nature of the gastrointestinal tract microbiome and its potentional risk factors for dysbiosis in order to tailor its application to the individual patient and create an era of highly personalized, precision medicine.
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Affiliation(s)
- Karan Grover
- Department of Surgery, Rutgers Biomedical Health Sciences-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Stephanie Gregory
- Department of Surgery, Rutgers Biomedical Health Sciences-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - John F Gibbs
- Department of Surgery, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
| | - Nancy J Emenaker
- Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA
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14
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Yano Y, Etemadi A, Abnet CC. Microbiome and Cancers of the Esophagus: A Review. Microorganisms 2021; 9:1764. [PMID: 34442842 PMCID: PMC8398938 DOI: 10.3390/microorganisms9081764] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/11/2021] [Accepted: 08/14/2021] [Indexed: 01/04/2023] Open
Abstract
Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.
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Affiliation(s)
- Yukiko Yano
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (A.E.); (C.C.A.)
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15
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Ma T, Ru J, Xue J, Schulz S, Mirzaei MK, Janssen KP, Quante M, Deng L. Differences in Gut Virome Related to Barrett Esophagus and Esophageal Adenocarcinoma. Microorganisms 2021; 9:microorganisms9081701. [PMID: 34442780 PMCID: PMC8401523 DOI: 10.3390/microorganisms9081701] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 08/01/2021] [Accepted: 08/06/2021] [Indexed: 12/22/2022] Open
Abstract
The relationship between viruses (dominated by bacteriophages or phages) and lower gastrointestinal (GI) tract diseases has been investigated, whereas the relationship between gut bacteriophages and upper GI tract diseases, such as esophageal diseases, which mainly include Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), remains poorly described. This study aimed to reveal the gut bacteriophage community and their behavior in the progression of esophageal diseases. In total, we analyzed the gut phage community of sixteen samples from patients with esophageal diseases (six BE patients and four EAC patients) as well as six healthy controls. Differences were found in the community composition of abundant and rare bacteriophages among three groups. In addition, the auxiliary metabolic genes (AMGs) related to bacterial exotoxin and virulence factors such as lipopolysaccharides (LPS) biosynthesis proteins were found to be more abundant in the genome of rare phages from BE and EAC samples compared to the controls. These results suggest that the community composition of gut phages and functional traits encoded by them were different in two stages of esophageal diseases. However, the findings from this study need to be validated with larger sample sizes in the future.
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Affiliation(s)
- Tianli Ma
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
| | - Jinlong Ru
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
| | - Jinling Xue
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
| | - Sarah Schulz
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
| | - Mohammadali Khan Mirzaei
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
| | - Klaus-Peter Janssen
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany;
| | - Michael Quante
- II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany
- Innere Medizin II, Universitätsklinik Freiburg, Universität Freiburg, 79106 Freiburg, Germany
- Correspondence: (M.Q.); (L.D.)
| | - Li Deng
- Helmholtz Centre Munich—German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany; (T.M.); (J.R.); (J.X.); (S.S.); (M.K.M.)
- Institute of Virology, Technical University of Munich, 81675 Munich, Germany
- Correspondence: (M.Q.); (L.D.)
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16
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Porphyromonas gingivalis infection exacerbates oesophageal cancer and promotes resistance to neoadjuvant chemotherapy. Br J Cancer 2021; 125:433-444. [PMID: 33981017 PMCID: PMC8329259 DOI: 10.1038/s41416-021-01419-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 03/30/2021] [Accepted: 04/22/2021] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The effect of Porphyromonas gingivalis (Pg) infection on oesophageal squamous cell carcinoma (ESCC) prognosis, chemotherapeutic efficacy, and oesophageal cancer cell apoptosis resistance and proliferation remain poorly understood. METHODS Clinicopathological data from 312 ESCC oesophagectomy patients, along with the computed tomography imaging results and longitudinal cancerous tissue samples from a patient subset (n = 85) who received neoadjuvant chemotherapy (NACT), were analysed. Comparison of overall survival and response rate to NACT between Pg-infected and Pg-uninfected patients was made by multivariate Cox analysis and Response Evaluation Criteria in Solid Tumours v.1.1 criteria. The influence of Pg on cell proliferation and drug-induced apoptosis was examined in ESCC patients and validated in vitro and in vivo. RESULTS The 5-year overall survival was lower in Pg-positive patients, and infection was associated with multiple clinicopathological factors and pathologic tumour, node, metastasis stage. Of the 85 patients who received NACT, Pg infection was associated with a lower response rate and 5-year overall survival. Infection with Pg resulted in apoptosis resistance in ESCC and promoted ESCC cell viability, which was confirmed in longitudinal cancerous tissue samples. Pg-induced apoptosis resistance was dependent on fimbriae and STAT3. CONCLUSIONS Pg infection is associated with a worse ESCC prognosis, reduced chemotherapy efficacy, and can potentiate the aggressive behaviour of ESCC cells.
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Nortunen M, Väkiparta N, Porvari K, Saarnio J, Karttunen TJ, Huhta H. Pathophysiology of reflux oesophagitis: role of Toll-like receptors 2 and 4 and Farnesoid X receptor. Virchows Arch 2021; 479:285-293. [PMID: 33686512 PMCID: PMC8364528 DOI: 10.1007/s00428-021-03066-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 01/15/2021] [Accepted: 02/18/2021] [Indexed: 11/28/2022]
Abstract
The pathogenesis of gastroesophageal reflux disease (GERD) is not fully understood. It involves the activation of mucosal immune-mediated and inflammatory responses. Toll-like receptors (TLR) 2 and TLR4 are pattern-recognition receptors of the innate immune system; they recognize microbial and endogenous ligands. Farnesoid X receptor (FXR) is a bile acid receptor that regulates the inflammatory response. We aimed to evaluate TLR2, TLR4 and FXR expression patterns in GERD. We re-evaluated 84 oesophageal biopsy samples according to the global severity (GS) score, including 26 cases with histologically normal oesophagus, 28 with histologically mild oesophagitis and 30 with severe oesophagitis. We used immunohistochemistry and in situ hybridization to assess the expression patterns of TLR2, TLR4 and FXR in oesophageal squamous cells. Immunohistochemistry showed that nuclear and cytoplasmic TLR2 was expressed predominantly in the basal layer of normal oesophageal epithelium. In oesophagitis, TLR2 expression increased throughout the epithelium, and the superficial expression was significantly more intensive compared to normal epithelium, p <0.01. Nuclear and cytoplasmic TLR4 was expressed throughout the thickness of squamous epithelium, with no change in oesophagitis. FXR was expressed in the nuclei of squamous cells, and the intensity of the expression increased significantly in oesophagitis (p <0.05). FXR expression correlated with basal TLR2. In situ hybridization confirmed the immunohistochemical expression patterns of TLR2 and TLR4. In GERD, TLR2, but not TLR4, expression was upregulated which indicates that innate immunity is activated according to a specific pattern in GERD. FXR expression was increased in GERD and might have a regulatory connection to TLR2.
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Affiliation(s)
- Minna Nortunen
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland.
- Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland.
- Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
| | - Nina Väkiparta
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
| | - Katja Porvari
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
| | - Juha Saarnio
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
- Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland
- Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
| | - Tuomo J Karttunen
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
| | - Heikki Huhta
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
- Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland
- Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
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18
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The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma. BIOLOGY 2021; 10:biology10080697. [PMID: 34439930 PMCID: PMC8389269 DOI: 10.3390/biology10080697] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/05/2021] [Accepted: 07/12/2021] [Indexed: 12/20/2022]
Abstract
Simple Summary Esophageal adenocarcinoma has a poor 5-year survival rate and is among the highest mortality cancers. Changes in the esophageal microbiome have been associated with cancer pathogenesis; however, the molecular mechanism remains obscure. This review article critically analyzes the molecular mechanisms through which microbiota may mediate the development and progression of esophageal adenocarcinoma and its precursors-gastroesophageal reflux disease and Barrett’s esophagus. It summarizes changes in esophageal microbiome composition in normal and pathologic states and subsequently discusses the role of altered microbiota in disease progression. The potential role of esophageal microbiota in protecting against the development of esophageal adenocarcinoma is also discussed. By doing so, this article highlights specific directions for future research developing microbiome-mediated therapeutics for esophageal adenocarcinoma. Abstract Esophageal adenocarcinoma (EAC) is associated with poor overall five-year survival. The incidence of esophageal cancer is on the rise, especially in Western societies, and the pathophysiologic mechanisms by which EAC develops are of extreme interest. Several studies have proposed that the esophageal microbiome may play an important role in the pathophysiology of EAC, as well as its precursors—gastroesophageal reflux disease (GERD) and Barrett’s esophagus (BE). Gastrointestinal microbiomes altered by inflammatory states have been shown to mediate tumorigenesis directly and are now being considered as novel targets for both cancer treatment and prevention. Elucidating molecular mechanisms through which the esophageal microbiome potentiates the development of GERD, BE, and EAC will provide a foundation on which new therapeutic targets can be developed. This review summarizes current findings that elucidate the molecular mechanisms by which microbiota promote the pathogenesis of GERD, BE, and EAC, revealing potential directions for additional research on the microbiome-mediated pathophysiology of EAC.
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Mennini M, Tambucci R, Riccardi C, Rea F, De Angelis P, Fiocchi A, Assa'ad A. Eosinophilic Esophagitis and Microbiota: State of the Art. Front Immunol 2021; 12:595762. [PMID: 33679739 PMCID: PMC7933523 DOI: 10.3389/fimmu.2021.595762] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.
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Affiliation(s)
- Maurizio Mennini
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Renato Tambucci
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Carla Riccardi
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Francesca Rea
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Paola De Angelis
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Alessandro Fiocchi
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Amal Assa'ad
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
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20
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Come J, Pereira JB, Pinto R, Carrilho C, Pereira L, Lara Santos L. The Upper Digestive Tract Microbiome and Oesophageal Squamous Cell Carcinoma: Epidemiology, Pathogenesis, and Clinical Implications in Africa. Pathobiology 2020; 88:141-155. [PMID: 33291118 DOI: 10.1159/000511422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 09/07/2020] [Indexed: 12/24/2022] Open
Abstract
The study of the microbiome has significantly contributed to our understanding of complex diseases including cancer, with a profound influence of the microbiota on clinical prognosis and the efficacy of cancer treatments. Oesophageal cancer is positioned amongst the most aggressive malignant diseases, resulting from a complex interaction between anthropometric, genetic, immune response, and environmental factors. Oesophageal squamous cell carcinoma (OSCC) is the most common type of oesophageal cancer and is a serious burden in Eastern Africa, in the area known as the African oesophageal cancer corridor (AOCC). OSCC is often diagnosed at a late stage, with patients already suffering from severe malnutrition and dehydration due to swallowing difficulties, leading to high mortality rates. So far, aetiological factors have been individually analysed with an inappropriate contextualisation. The upper digestive tract microbiome has been proposed to contribute to the onset and progression of OSCC but with limited understanding of the mechanisms behind this interaction. Data on African populations are limited, and the aetiology of AOCC is still poorly understood. This review discusses the current knowledge of the aetiology of OSCC in Africa, with special focus on the probable influence of the upper digestive tract microbiota.
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Affiliation(s)
- Jotamo Come
- Departamento de Cirurgia, Hospital Central de Maputo, Maputo, Mozambique
| | - Joana Barbosa Pereira
- i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
| | - Ricardo Pinto
- i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
| | - Carla Carrilho
- Departamento de Patologia, Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique.,Departamento de Patologia, Hospital Central de Maputo, Maputo, Mozambique
| | - Luisa Pereira
- i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
| | - Lúcio Lara Santos
- Grupo de Patologia e Terapêutica Experimental e Departamento de Oncologia do Instituto Português de Oncologia do Porto, Porto, Portugal, .,ONCOCIR - Education and Care in Oncology, PALOP - Lusophone Africa, Porto, Portugal,
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21
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Garman KS, Ajayi TA, Boutte HJ, Chiu ST, von Furstenberg RJ, Lloyd BR, Zhang C, Onaitis MW, Chow SC, McCall SJ. Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma. PLoS One 2020; 15:e0235906. [PMID: 32697782 PMCID: PMC7375530 DOI: 10.1371/journal.pone.0235906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 06/03/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.
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Affiliation(s)
- Katherine S. Garman
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Teminioluwa A. Ajayi
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Harold J. Boutte
- Division of Gastroenterology, Department of Medicine, Northwestern Medicine, Chicago, Illinois, United States of America
| | - Shih-Ting Chiu
- Providence Health and Services, Portland, Oregon, United States of America
| | - Richard J. von Furstenberg
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Benjamin R. Lloyd
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Cecelia Zhang
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Mark W. Onaitis
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, University of California San Diego, La Jolla, California, United States of America
| | - Shein-Chung Chow
- Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America
| | - Shannon J. McCall
- Department of Pathology, Duke University, Durham, North Carolina, United States of America
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22
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Zhou J, Shrestha P, Qiu Z, Harman DG, Teoh WC, Al-Sohaily S, Liem H, Turner I, Ho V. Distinct Microbiota Dysbiosis in Patients with Non-Erosive Reflux Disease and Esophageal Adenocarcinoma. J Clin Med 2020; 9:jcm9072162. [PMID: 32650561 PMCID: PMC7408827 DOI: 10.3390/jcm9072162] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/03/2020] [Accepted: 07/06/2020] [Indexed: 02/06/2023] Open
Abstract
Non-erosive reflux disease (NERD) and esophageal adenocarcinoma (EAC) are often regarded as bookends in the gastroesophageal reflux disease spectrum. However, there is limited clinical evidence to support this disease paradigm while the underlying mechanisms of disease progression remain unclear. In this study, we used 16S rRNA sequencing and mass-spectrometer-based proteomics to characterize the esophageal microbiota and host mucosa proteome, respectively. A total of 70 participants from four patient groups (NERD, reflux esophagitis, Barrett’s esophagus, and EAC) and a control group were analyzed. Our results showed a unique NERD microbiota composition, distinct to control and other groups. We speculate that an increase in sulfate-reducing Proteobacteria and Bacteroidetes along with hydrogen producer Dorea are associated with a mechanistic role in visceral hypersensitivity. We also observed a distinct EAC microbiota consisting of a high abundance of lactic acid-producing bacteria (Staphylococcus, Lactobacillus, Bifidobacterium, and Streptococcus), which may contribute towards carcinogenesis through dysregulated lactate metabolism. This study suggests the close relationship between esophageal mucosal microbiota and the appearance of pathologies of this organ.
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Affiliation(s)
- Jerry Zhou
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Correspondence: ; Tel.: +61-2-4620-3865
| | - Prapti Shrestha
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
| | - Zhiguang Qiu
- Hawkesbury Institute for the Environment, Western Sydney University, Penrith, NSW 2750, Australia;
| | - David G. Harman
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
| | - Wun-Chung Teoh
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Sam Al-Sohaily
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Han Liem
- Nepean Hospital, Kingswood, NSW 2747, Australia;
| | - Ian Turner
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
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23
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Zhang X, Pan Z. Influence of microbiota on immunity and immunotherapy for gastric and esophageal cancers. Gastroenterol Rep (Oxf) 2020; 8:206-214. [PMID: 32665852 PMCID: PMC7333930 DOI: 10.1093/gastro/goaa014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/05/2020] [Accepted: 03/11/2020] [Indexed: 12/13/2022] Open
Abstract
Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer.
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Affiliation(s)
- Xiaoli Zhang
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
| | - Zui Pan
- College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, TX, USA
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Steve M D, Lindsey B C, Byung Soo Y, Parth J P, David A J. Microbiome and Gastroesophageal Disease: Pathogenesis and Implications for Therapy. ACTA ACUST UNITED AC 2020. [DOI: 10.29328/journal.acgh.1001018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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25
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F. Escapa I, Huang Y, Chen T, Lin M, Kokaras A, Dewhirst FE, Lemon KP. Construction of habitat-specific training sets to achieve species-level assignment in 16S rRNA gene datasets. MICROBIOME 2020; 8:65. [PMID: 32414415 PMCID: PMC7291764 DOI: 10.1186/s40168-020-00841-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 04/15/2020] [Indexed: 05/10/2023]
Abstract
BACKGROUND The low cost of 16S rRNA gene sequencing facilitates population-scale molecular epidemiological studies. Existing computational algorithms can resolve 16S rRNA gene sequences into high-resolution amplicon sequence variants (ASVs), which represent consistent labels comparable across studies. Assigning these ASVs to species-level taxonomy strengthens the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies and further facilitates data comparison across studies. RESULTS To achieve this, we developed a broadly applicable method for constructing high-resolution training sets based on the phylogenic relationships among microbes found in a habitat of interest. When used with the naïve Bayesian Ribosomal Database Project (RDP) Classifier, this training set achieved species/supraspecies-level taxonomic assignment of 16S rRNA gene-derived ASVs. The key steps for generating such a training set are (1) constructing an accurate and comprehensive phylogenetic-based, habitat-specific database; (2) compiling multiple 16S rRNA gene sequences to represent the natural sequence variability of each taxon in the database; (3) trimming the training set to match the sequenced regions, if necessary; and (4) placing species sharing closely related sequences into a training-set-specific supraspecies taxonomic level to preserve subgenus-level resolution. As proof of principle, we developed a V1-V3 region training set for the bacterial microbiota of the human aerodigestive tract using the full-length 16S rRNA gene reference sequences compiled in our expanded Human Oral Microbiome Database (eHOMD). We also overcame technical limitations to successfully use Illumina sequences for the 16S rRNA gene V1-V3 region, the most informative segment for classifying bacteria native to the human aerodigestive tract. Finally, we generated a full-length eHOMD 16S rRNA gene training set, which we used in conjunction with an independent PacBio single molecule, real-time (SMRT)-sequenced sinonasal dataset to validate the representation of species in our training set. This also established the effectiveness of a full-length training set for assigning taxonomy of long-read 16S rRNA gene datasets. CONCLUSION Here, we present a systematic approach for constructing a phylogeny-based, high-resolution, habitat-specific training set that permits species/supraspecies-level taxonomic assignment to short- and long-read 16S rRNA gene-derived ASVs. This advancement enhances the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies. Video Abstract.
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Affiliation(s)
- Isabel F. Escapa
- Forsyth Institute (Microbiology), Cambridge, MA USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA USA
- Department of Molecular Virology & Microbiology, Alkek Center for Metagenomics & Microbiome Research, Baylor College of Medicine, Houston, TX USA
| | - Yanmei Huang
- Forsyth Institute (Microbiology), Cambridge, MA USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA USA
| | - Tsute Chen
- Forsyth Institute (Microbiology), Cambridge, MA USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA USA
| | - Maoxuan Lin
- Forsyth Institute (Microbiology), Cambridge, MA USA
| | | | - Floyd E. Dewhirst
- Forsyth Institute (Microbiology), Cambridge, MA USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA USA
| | - Katherine P. Lemon
- Forsyth Institute (Microbiology), Cambridge, MA USA
- Department of Molecular Virology & Microbiology, Alkek Center for Metagenomics & Microbiome Research, Baylor College of Medicine, Houston, TX USA
- Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA
- Section of Infectious Diseases, Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX USA
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26
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Park CH, Lee SK. Exploring Esophageal Microbiomes in Esophageal Diseases: A Systematic Review. J Neurogastroenterol Motil 2020; 26:171-179. [PMID: 32235026 PMCID: PMC7176507 DOI: 10.5056/jnm19240] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 02/11/2020] [Accepted: 02/27/2020] [Indexed: 12/12/2022] Open
Abstract
Studies that investigated esophageal microbiomes are limited when compared to those on intestinal microbiomes. Nevertheless, several studies have investigated the relationship between esophageal microbiomes and various esophageal diseases, owing to the advancement of next-generation sequencing techniques. Streptococcus is the most common bacterial taxon in a normal esophagus. Additionally, Haemophilus, Neisseria, Prevotella, and Veillonella are also found. However, gram-negative bacteria, including Prevotella, are more abundant in a diseased esophagus, such as in gastroesophageal reflux disease and Barrett’ esophagus. This systematic review aims to summarize current evidences on esophageal microbiomes in various esophageal diseases.
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Affiliation(s)
- Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Jung HK, Hong SJ, Lee OY, Pandolfino J, Park H, Miwa H, Ghoshal UC, Mahadeva S, Oshima T, Chen M, Chua ASB, Cho YK, Lee TH, Min YW, Park CH, Kwon JG, Park MI, Jung K, Park JK, Jung KW, Lim HC, Jung DH, Kim DH, Lim CH, Moon HS, Park JH, Choi SC, Suzuki H, Patcharatrakul T, Wu JCY, Lee KJ, Tanaka S, Siah KTH, Park KS, Kim SE. 2019 Seoul Consensus on Esophageal Achalasia Guidelines. J Neurogastroenterol Motil 2020; 26:180-203. [PMID: 32235027 PMCID: PMC7176504 DOI: 10.5056/jnm20014] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/08/2020] [Indexed: 12/13/2022] Open
Abstract
Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - John Pandolfino
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Hyojin Park
- Division of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Yu Kyung Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University Hospital, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jong Kyu Park
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Hyun Lim
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea
| | - Hidekazu Suzuki
- Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tanisa Patcharatrakul
- Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
| | - Shinwa Tanaka
- Department of Gastroenterology, Kobe University Hospital, Hyogo, Japan
| | - Kewin T H Siah
- Division of Gastroenterology and Hepatology, National University Health System, Singapore City, Singapore
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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Singh R, Balasubramanian I, Zhang L, Gao N. Metaplastic Paneth Cells in Extra-Intestinal Mucosal Niche Indicate a Link to Microbiome and Inflammation. Front Physiol 2020; 11:280. [PMID: 32296343 PMCID: PMC7138011 DOI: 10.3389/fphys.2020.00280] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 03/12/2020] [Indexed: 12/12/2022] Open
Abstract
Paneth cells are residents of the intestinal epithelium. Abnormal appearance of Paneth cells has been widely documented in non-intestinal tissues within the digestive tract and even observed in non-gastrointestinal organs. Although metaplastic Paneth cells are part of the overarching pathology of intestinal metaplasia (IM), only a fraction of intestinal metaplastic lesions contain Paneth cells. We survey literature documenting metaplastic Paneth cells to gain insights into mechanism underlying their etiologic development as well as their potential relevance to human health. A synthesized view from this study suggests that the emergence of metaplastic Paneth cells at extra-intestinal mucosal sites likely represents a protective, anti-bacterial, and inflammatory response evoked by an altered microbial activity.
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Affiliation(s)
- Rajbir Singh
- Department of Biological Sciences, Rutgers University, Newark, NJ, United States
| | | | - Lanjing Zhang
- Department of Biological Sciences, Rutgers University, Newark, NJ, United States.,Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, United States.,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States.,Department of Pathology, Princeton Medical Center, Plainsboro, NJ, United States
| | - Nan Gao
- Department of Biological Sciences, Rutgers University, Newark, NJ, United States.,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
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29
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Rajilic-Stojanovic M, Figueiredo C, Smet A, Hansen R, Kupcinskas J, Rokkas T, Andersen L, Machado JC, Ianiro G, Gasbarrini A, Leja M, Gisbert JP, Hold GL. Systematic review: gastric microbiota in health and disease. Aliment Pharmacol Ther 2020; 51:582-602. [PMID: 32056247 DOI: 10.1111/apt.15650] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/09/2020] [Accepted: 01/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is the most infamous constituent of the gastric microbiota and its presence is the strongest risk factor for gastric cancer and other gastroduodenal diseases. Although historically the healthy stomach was considered a sterile organ, we now know it is colonised with a complex microbiota. However, its role in health and disease is not well understood. AIM To systematically explore the literature on the gastric microbiota in health and disease as well as the gut microbiota after bariatric surgery. METHODS A systematic search of online bibliographic databases MEDLINE/EMBASE was performed between 1966 and February 2019 with screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomised controlled trials, cohort studies and observational studies were included if they reported next-generation sequencing derived microbiota analysis on gastric aspirate/tissue or stool samples (bariatric surgical outcomes). RESULTS Sixty-five papers were eligible for inclusion. With the exception of H pylori-induced conditions, overarching gastric microbiota signatures of health or disease could not be determined. Gastric carcinogenesis induces a progressively altered microbiota with an enrichment of oral and intestinal taxa as well as significant changes in host gastric mucin expression. Proton pump inhibitors usage increases gastric microbiota richness. Bariatric surgery is associated with an increase in potentially pathogenic proteobacterial species in patient stool samples. CONCLUSION While H pylori remains the single most important risk factor for gastric disease, its capacity to shape the collective gastric microbiota remains to be fully elucidated. Further studies are needed to explore the intricate host/microbial and microbial/microbial interplay.
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30
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The oncogenic roles of bacterial infections in development of cancer. Microb Pathog 2020; 141:104019. [PMID: 32006638 DOI: 10.1016/j.micpath.2020.104019] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 01/03/2020] [Accepted: 01/28/2020] [Indexed: 12/12/2022]
Abstract
Initiation of cancer is interconnected with different factors like infections. It has been estimated that infections, particularly viruses, participate in about 20% of all cancers. Bacteria as the most common infectious agents are also reported to be emerging players in the establishment of malignant cells. Microbial infections are able to modulate host cell transformation for promoting malignant features through the production of carcinogenic metabolites participating in inflammation responses, disruption of cell metabolism, and integrity and also genomic or epigenetic manipulations. It seems that the best example of the role of bacteria in cancer promotion is Helicobacter pylori infection, which is related to gastric cancer. World Health Organization (WHO) describes bacterium as class I carcinogens. Several bacterial infections have been reported in association with prevalent cancers. In this review, we will summarize the role of known bacterial infections in the initiation of the main common cancers, which show high mortality in the world. Examining the microbiomes in cancer patients is important and necessary to better understand the pathogenesis of this disease and also to plan therapeutic interventions.
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31
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Li M, Shao D, Zhou J, Gu J, Qin J, Chen W, Wei W. Signatures within esophageal microbiota with progression of esophageal squamous cell carcinoma. Chin J Cancer Res 2020; 32:755-767. [PMID: 33446998 PMCID: PMC7797230 DOI: 10.21147/j.issn.1000-9604.2020.06.09] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective Esophageal squamous cell carcinoma (ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions. Methods Paired esophageal biopsy and swab specimens were obtained from 236 participants in Linzhou, China. Data from 16S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology (QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model. Results Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit (OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include Streptococcus, Prevotella, Veillonella, Actinobacillus, Haemophilus, Neisseria, Alloprevotella, Rothia, Gemella and Porphyromonas. Genus Streptococcus, Haemophilus, Neisseria and Porphyromonas showed significantly difference in disease groups when compared to normal control, whereas Streptococcus showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken Streptococcus and Neisseria into model, the prediction performance was the ideal one, of which the area under the curve (AUC) was 0.738.
Conclusions Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of Streptococcus and Neisseria has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.
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Affiliation(s)
- Minjuan Li
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dantong Shao
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiachen Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jianhua Gu
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Junjie Qin
- Promegene Translational Research Institute, Shenzhen 518000, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Degiovani M, Ribas CAPM, Czeczko NG, Parada AA, Fronchetti JDA, Malafaia O. IS THERE A RELATION BETWEEN HELYBACTER PYLORI AND INTESTINAL METAPLASIA IN SHORT COLUMN EPITELIZATION UP TO 10 MM IN THE DISTAL ESOPHAGUS? ACTA ACUST UNITED AC 2019; 32:e1480. [PMID: 31859933 PMCID: PMC6918731 DOI: 10.1590/0102-672020190001e1480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 05/08/2019] [Indexed: 12/16/2022]
Abstract
Background: The presence of intestinal metaplasia in the distal esophagus (Barrett’s esophagus) is an important precursor of adenocarcinoma. Knowledge of the risk factors and the process by which the Barrett develops is very important and Helicobacter pylori (HP) can contribute to this development. Aim: To analyze the impact of HP in the gastric mucosa with intestinal metaplasia in the distal esophagus in areas of columnar epithelialization smaller than 10 mm in length and epidemiological data on prevalence Method: A retrospective study in which were included 373 consecutive patients diagnosed with columnar epithelium in the distal esophagus was done. In all, HP was investigated by urease and histology, exclusion and inclusion factors were applied and patients were divided into two groups: the first grouping the ones without histological diagnosis of Barrett’s esophagus (235-63%) and the second with it (138-37%). Results: There was no significant difference between HP and non-HP patients in relation to the probability of having intestinal metaplasia (p=0.587). When related to the general group, there was an inverse association between the bacterium and the columnar epithelia in the distal esophagus. Age (p=0.031), gender (p=0.013) and HP (p=0.613) when related together to intestinal metaplasia showed no significant relation. In isolation, when related to age and gender, regardless of HP, results confirmed that patients in more advanced age and women present a higher incidence of intestinal metaplasia. Conclusion: There is an inverse relation between HP and the areas of columnar epithelization in the distal esophagus, regardless of the presence or absence of intestinal metaplasia. Age and gender, regardless of HP, showed higher prevalence in women and in older the number of cases with intestinal metaplasia in the distal esophagus.
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Affiliation(s)
- Matheus Degiovani
- Postgraduate Program in Principles of Surgery, Mackenzie Evangelical School of Medicine - Paraná, Curitiba, PR, Brazil.,Digestive Endoscopy Service, 9 de Julho Hospital, São Paulo, SP, Brazil
| | | | - Nicolau Gregori Czeczko
- Postgraduate Program in Principles of Surgery, Mackenzie Evangelical School of Medicine - Paraná, Curitiba, PR, Brazil
| | - Artur Adolfo Parada
- Postgraduate Program in Principles of Surgery, Mackenzie Evangelical School of Medicine - Paraná, Curitiba, PR, Brazil.,Digestive Endoscopy Service, 9 de Julho Hospital, São Paulo, SP, Brazil
| | - Juliana de Andrade Fronchetti
- Postgraduate Program in Principles of Surgery, Mackenzie Evangelical School of Medicine - Paraná, Curitiba, PR, Brazil
| | - Osvaldo Malafaia
- Postgraduate Program in Principles of Surgery, Mackenzie Evangelical School of Medicine - Paraná, Curitiba, PR, Brazil
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Liu AQ, Vogtmann E, Shao DT, Abnet CC, Dou HY, Qin Y, Su Z, Wei WQ, Chen W. A Comparison of Biopsy and Mucosal Swab Specimens for Examining the Microbiota of Upper Gastrointestinal Carcinoma. Cancer Epidemiol Biomarkers Prev 2019; 28:2030-2037. [PMID: 31519703 PMCID: PMC7294753 DOI: 10.1158/1055-9965.epi-18-1210] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 04/11/2019] [Accepted: 09/10/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND There is currently no optimal sampling method for upper gastrointestinal (UGI) tract microbiota. We compared biopsies and mucosal swab specimens for microbial sampling from patients with UGI carcinoma. METHODS A total of 67 patients with esophageal squamous cell carcinoma (ESCC) and 36 patients with gastric cardia adenocarcinoma (GCA) were recruited in the Linxian Cancer Hospital (Henan, China). Sterile biopsies and swabs were used to collect paired samples from the resection specimens from carcinoma and adjacent normal tissue. Data from 16S rRNA gene sequencing were processed using QIIME2 to evaluate differences in alpha and beta diversity and taxonomic relative abundances between specimen types. RESULTS Alpha diversity was not significantly different between swab specimens and biopsies, both for ESCC and GCA. Paired specimens were correlated for both sample types from ESCC (ρ > 0.6, P < 0.001) but not GCA (ρ < 0.4, P > 0.05). For beta diversity, distinct clustering by sampling method was not observed for adjacent normal or tumor tissue from ESCC or GCA. There was a high correlation for weighted UniFrac and Bray-Curtis distance only in ESCC paired specimens (ρ > 0.6, P = 0.001). The 10 dominant bacterial genera were similar between swab and biopsy specimens. However, higher levels of Veillonella (P = 0.0002) and Streptococcus (P = 0.0002) were detected in ESCC adjacent normal and GCA carcinoma swabs, respectively, compared with the biopsies. CONCLUSIONS Mucosal swab specimens and biopsies could yield similar microbial profiles from ESCC but not GCA. Both can be used to characterize UGI microbiota; one sampling method should be selected for future studies. IMPACT This study provides insight for planning microbiota collections from the UGI tract.
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Affiliation(s)
- An-Qi Liu
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Emily Vogtmann
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland
| | - Dan-Tong Shao
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland
| | - Hao-Yu Dou
- Promegene Translational Research Institute, Shenzhen, China
| | - Yu Qin
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Su
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-Qiang Wei
- Cancer Registration Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Impact of the Gastrointestinal Microbiome in Health and Disease: Co-evolution with the Host Immune System. Curr Top Microbiol Immunol 2019; 421:303-318. [PMID: 31123894 DOI: 10.1007/978-3-030-15138-6_12] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Microbes within the gastrointestinal tract communicate with each other and with the host, which has profound effects on health and disease development. Only now, it is becoming apparent that how and when we acquire our own unique collection of "gut microbes" and also how we choose to maintain them is fundamental to our health. Helicobacter pylori is the most common bacterial infection worldwide, colonizing around half of the world's population, and is the major risk factor for gastric adenocarcinoma. More recently, it has also been shown to have some beneficial effects in terms of protecting against the development of other diseases. Here, we review the current knowledge on how H. pylori has shaped gastrointestinal microbiota colonization and the host immune system with specific focus on the impact of H. pylori on the various microbiome niches of the gastrointestinal tract. We discuss how the presence of H. pylori influences the physiology of three major regions within the gastrointestinal tract-specifically the oesophagus, stomach and colon. We pay particular attention to the role of H. pylori under chronic inflammatory conditions including the development of cancer. With increased incidence of diseases such as eosinophilic oesophagitis, oesophageal adenocarcinoma and squamous cell carcinoma being attributed to the decline in H. pylori, their disease pathogenesis in light of changing H. pylori colonization is also discussed.
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Ajayi TA, Cantrell S, Spann A, Garman KS. Barrett's esophagus and esophageal cancer: Links to microbes and the microbiome. PLoS Pathog 2018; 14:e1007384. [PMID: 30571768 PMCID: PMC6301555 DOI: 10.1371/journal.ppat.1007384] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Teminioluwa A Ajayi
- School of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Sarah Cantrell
- School of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Ashley Spann
- Department of Medicine, Duke University, Durham, North Carolina, United States of America
| | - Katherine S Garman
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, United States of America.,Durham Veterans Affairs Health Care System, Durham, North Carolina, United States of America
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Escapa IF, Chen T, Huang Y, Gajare P, Dewhirst FE, Lemon KP. New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract. mSystems 2018; 3:e00187-18. [PMID: 30534599 PMCID: PMC6280432 DOI: 10.1128/msystems.00187-18] [Citation(s) in RCA: 361] [Impact Index Per Article: 51.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 11/02/2018] [Indexed: 12/22/2022] Open
Abstract
The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.
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Affiliation(s)
- Isabel F. Escapa
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Tsute Chen
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Yanmei Huang
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Prasad Gajare
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
| | - Floyd E. Dewhirst
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Katherine P. Lemon
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Abstract
PURPOSE OF REVIEW Investigation of the esophageal microbiome is a relatively new field. This review will outline data characterizing the esophageal microbiome in both health and disease states, including gastroesophageal reflux disease (GERD), Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, and motility disorders. RECENT FINDINGS While the esophagus was previously considered devoid of a significant bacterial population, development of culture-independent techniques, specifically 16S rRNA gene sequencing, as well as novel, minimally invasive microbial sampling modalities, has facilitated characterization of the esophageal microbiome in both health and several disease states. Although limited, there is evidence that the esophagus contains a diverse microbial population, with Gram-positive bacteria, specifically Streptococcus, dominating in health, while Gram-negative bacteria prevail in reflux disorders including GERD and Barrett's esophagus. The microbiome is altered with other esophageal disorders as well, including eosinophilic esophagitis and esophageal motility disorders, though these changes have been less well characterized. Characterization of the gut microbiome has advanced significantly; however, further investigation is essential. Understanding changes in the esophageal microbiome could affect our understanding of the natural history of diseases of the esophagus and present potential therapeutic approaches.
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Affiliation(s)
- Brooke Corning
- Division of Gastroenterology and Hepatology, University of Virginia Health System, 1300 Jefferson Park Avenue Multi Story Building Room 2091, Charlottesville, VA, 22908, USA
| | - Andrew P Copland
- Division of Gastroenterology and Hepatology, University of Virginia Health System, 1300 Jefferson Park Avenue Multi Story Building Room 2091, Charlottesville, VA, 22908, USA
| | - Jeanetta W Frye
- Division of Gastroenterology and Hepatology, University of Virginia Health System, 1300 Jefferson Park Avenue Multi Story Building Room 2091, Charlottesville, VA, 22908, USA.
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Dong L, Yin J, Zhao J, Ma SR, Wang HR, Wang M, Chen W, Wei WQ. Microbial Similarity and Preference for Specific Sites in Healthy Oral Cavity and Esophagus. Front Microbiol 2018; 9:1603. [PMID: 30065718 PMCID: PMC6056649 DOI: 10.3389/fmicb.2018.01603] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 06/27/2018] [Indexed: 12/11/2022] Open
Abstract
Human microbial communities are highly complex ecosystems, but it remains unclear if microbial compositions have any similarity in distinct sites of the oral cavity and esophagus in particular. Clinical samples were collected from three niches (saliva, tongue dorsum and supragingival plaque) of the oral cavity and three segments (upper, middle, and lower) of the esophagus in 27 healthy individuals. Bacterial V3-V4 region of 16S rRNA gene in these samples was amplified and sequenced on Illumina sequencing platform, followed by data analysis using QIIME and LEfSe softwares. Highly diverse bacterial flora with 365 genera belonging to 29 phyla resided in the oral cavity and 594 genera belonging to 29 phyla in the esophagus. The phyla Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and TM7 were most abundant in both the oral cavity and the esophagus, but the phyla Actinobacteria and Bacteroidetes were preferable in the oral cavity and Firmicutes in the esophagus. The genera Streptococcus, Neisseria, Prevotella, Actinobacillus, and Veillonella were most abundant in both oral cavity and esophagus, but Neisseria was preferable in the oral cavity and Streptococcus in the esophagus. Different niche-specific bacterial signatures were found in the oral cavity, e.g., the class Flavobacteria in the supragingival plaque, class Bacteroides in the saliva and the class Clostridia in the tongue dorsum. By contrast, no site specific bacteria for three different segments of esophagus were found. However, high variability of microbial compositions between individuals was observed. In conclusion, this study confirmed microbial diversity at different taxonomic levels in healthy oral cavity and esophagus, and identified the site-preferable bacterial signatures in six niches of the upper digestive tract. These findings provide a critical baseline for future studies interpreting microbiome-related diseases.
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Affiliation(s)
- Li Dong
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Jian Yin
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Zhao
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shan-Rui Ma
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hai-Rui Wang
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meng Wang
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Chen
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-Qiang Wei
- Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Gopal P, Gibson JA, Lisovsky M, Nalbantoglu ILK. Unique causes of esophageal inflammation: a histopathologic perspective. Ann N Y Acad Sci 2018; 1434:219-226. [PMID: 29766506 DOI: 10.1111/nyas.13732] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 03/16/2018] [Accepted: 03/20/2018] [Indexed: 12/18/2022]
Abstract
Gastroenterologists frequently perform endoscopic esophageal mucosal biopsies for pathologic diagnosis in patients experiencing symptoms of esophagitis. The more common causes of esophagitis diagnosed on esophageal mucosal biopsy include reflux esophagitis, eosinophilic esophagitis, and infectious esophagitis caused by Candida albicans, herpes simplex virus, and/or cytomegalovirus. However, there are several causes of esophagitis seen less frequently by pathologists that are very important to recognize. We discuss unique types of esophageal inflammation, including acute bacterial esophagitis, esophageal manifestations of dermatologic diseases, medication-induced esophageal injury, and sloughing esophagitis; and we review their clinical and histopathologic features.
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Affiliation(s)
- Purva Gopal
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Joanna A Gibson
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | - Mikhail Lisovsky
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - ILKe Nalbantoglu
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
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Cui ML, Wang JJ, Zhang MX. Role of microbiota in esophageal diseases. Shijie Huaren Xiaohua Zazhi 2018; 26:289-295. [DOI: 10.11569/wcjd.v26.i5.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent years, microbiota has become the focus of research, especially for the digestive system that contains a large number of bacteria. However, most studies are focused on the oral cavity, stomach, and intestine, and studies on the esophagus are few. This review summarizes the progress in research of microbiota in esophageal diseases, aiming to clarify the relationship between microbiota and esophageal diseases as well as the related mechanisms. This will be of importance in the diagnosis and treatment of esophageal diseases.
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Affiliation(s)
- Man-Li Cui
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Jing-Jie Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Ming-Xin Zhang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
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López-Gasca M, Peña J, García-Amado MA, Michelangeli F, Contreras M. Point Mutations at gyrA and gyrB Genes of Levofloxacin-Resistant Helicobacter pylori Isolates in the Esophageal Mucosa from a Venezuelan Population. Am J Trop Med Hyg 2018; 98:1051-1055. [PMID: 29405113 DOI: 10.4269/ajtmh.17-0478] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The treatment of Helicobacter pylori infection is complicated by antibiotic resistance. A high levofloxacin (LVX) resistance rate was previously demonstrated in H. pylori isolates from gastric mucosa (40%) and esophagus (19%) in individual hosts of a Venezuelan population. We aimed to assess the molecular mechanisms of LVX resistance and susceptibility in isolates from the gastroesophageal mucosa, by studying point mutations in the quinolone resistance-determining region of gyrA and gyrB genes. Sequencing of gyrA and gyrB genes (N = 120) helped to identify point mutations in 60 isolates (30 from antrum and 30 from esophagus) of five dyspeptic patients. Double (Asn87Thr and Asp91Asn) and single (Asn87Ile or Asn87Thr) mutations in the gyrA gene were identified in the esophageal mucosa. These mutations have been commonly found in the stomach. Occurrence of a single (Asn87Ile) mutation was associated with high resistance (minimum inhibitory concentration ≥ 32 μg/mL) to LVX. Only a single (Ser479Gly) mutation was found in the gyrB gene in both mucosae. One patient presented isolates with no mutations in the two genes studied. Isolates with the same mutation pattern in individual hosts revealed identical genetic profiles for these genes, confirming that isolates identified in the esophageal mucosa come from isolates colonizing the stomach. Helicobacter pylori resistance to LVX in the esophagus is related to double- and single-point mutations in gyrA and gyrB genes, such as those found in the stomach. Levofloxacin should be applied with caution, because its antibiotic effect on H. pylori is decreasing in Latin America, perhaps owing to high prescription rates.
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Affiliation(s)
- Mariela López-Gasca
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela
| | - Jessy Peña
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela
| | - María-Alexandra García-Amado
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela
| | - Fabián Michelangeli
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela
| | - Monica Contreras
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela
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Quante M, Graham TA, Jansen M. Insights Into the Pathophysiology of Esophageal Adenocarcinoma. Gastroenterology 2018; 154:406-420. [PMID: 29037468 DOI: 10.1053/j.gastro.2017.09.046] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 09/21/2017] [Accepted: 09/21/2017] [Indexed: 02/07/2023]
Abstract
Although researchers have identified genetic alterations that contribute to development of esophageal adenocarcinoma, we know little about features of patients or environmental factors that mediate progression of chronic acid biliary reflux to Barrett's esophagus and cancer. Increasing our understanding of the mechanisms by which normal squamous epithelium progresses to early-stage invasive cancer will help formulate rational surveillance guidelines and allow us to divest resources away from patients at low risk of malignancy. We review the cellular and genetic alterations that occur during progression of Barrett's esophagus, based on findings from clinical studies and mouse models of disease. We review the features of the luminal and mucosal microenvironment of Barrett's esophagus that promote, in a small proportion of patients, development of esophageal adenocarcinoma. Markers of clonal evolution can be used to determine patient risk for cancer and set surveillance intervals.
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Affiliation(s)
- Michael Quante
- II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
| | - Trevor A Graham
- Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Marnix Jansen
- University College London Cancer Institute, London, United Kingdom; University College London Hospital, London, United Kingdom
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Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H. Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications. Ann Gastroenterol Surg 2017; 1:99-104. [PMID: 29863142 PMCID: PMC5881342 DOI: 10.1002/ags3.12014] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 04/22/2017] [Indexed: 12/17/2022] Open
Abstract
Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum, which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.
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Affiliation(s)
- Yoshifumi Baba
- Department of Gastroenterological Surgery Graduate School of Medical Science Kumamoto University Kumamoto Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery Graduate School of Medical Science Kumamoto University Kumamoto Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery Graduate School of Medical Science Kumamoto University Kumamoto Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery Graduate School of Medical Science Kumamoto University Kumamoto Japan
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Ghebre YT, Raghu G. Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs. Am J Respir Crit Care Med 2017; 193:1345-52. [PMID: 27110898 DOI: 10.1164/rccm.201512-2316pp] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The prevalence of abnormal acid gastroesophageal reflux (GER) is higher in patients with idiopathic pulmonary fibrosis (IPF) than in matched control subjects. Several studies demonstrated that more than one-third of patients with IPF have abnormal esophageal acid exposures. In addition, many of these studies indicate that the majority of patients with IPF have silent reflux with no symptoms of GER. Findings of abnormal reflux persist in a large proportion of patients with IPF placed on antacid therapy such as proton pump inhibitors (PPIs). This seemingly paradoxical observation suggests that either patients with IPF are somehow resistant to PPI-based intervention or PPIs are inherently unable to suppress acid GER. By contrast, patients with IPF who undergo Nissen fundoplication surgery are effectively relieved from the complications of GER, and retrospective studies suggest improved lung function. Retrospective, anecdotal data suggest a beneficial role of PPIs in IPF including stabilization of lung function, reduction in episodes of acute exacerbation, and enhanced longevity. The recent evidence-based guidelines for treatment of IPF approved conditional recommendation of PPIs for all patients with IPF regardless of their GER status. Recently, we have reported that PPIs possess antiinflammatory and antifibrotic activities by directly suppressing proinflammatory cytokines, profibrotic proteins, and proliferation of lung fibroblasts. Our study provides an alternative explanation for the beneficial effect of PPIs in IPF. In this Perspective, we reviewed emerging progress on antifibrotic effect of PPIs using IPF as a disease model. In addition, we summarized surgical and pharmacological interventions for GER and their downstream effect on lung physiology.
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Affiliation(s)
- Yohannes T Ghebre
- 1 Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas; and
| | - Ganesh Raghu
- 2 Division of Pulmonary and Critical Care Medicine, Center for Interstitial Lung Disease, University of Washington, Seattle, Washington
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Zhang C, Powell SE, Betel D, Shah MA. The Gastric Microbiome and Its Influence on Gastric Carcinogenesis: Current Knowledge and Ongoing Research. Hematol Oncol Clin North Am 2017; 31:389-408. [PMID: 28501083 DOI: 10.1016/j.hoc.2017.01.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastric malignancies are a leading cause of cancer-related death worldwide. At least 2 microbial species are currently linked to carcinogenesis and the development of cancer within the human stomach. These include the bacterium Helicobacter pylori and the Epstein-Barr virus. In recent years, there has been increasing evidence that within the human gastrointestinal tract it is not only pathogenic microbes that impact human health but also the corresponding autochthonous microbial communities. This article reviews the gastrointestinal microbiome as it relates primarily to mechanisms of disease and carcinogenesis within the upper gastrointestinal tract.
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Affiliation(s)
- Chao Zhang
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
| | - Sarah Ellen Powell
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
| | - Doron Betel
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
| | - Manish A Shah
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Gastrointestinal Oncology Program, Center for Advanced Digestive Care, Sandra and Edward Meyer Cancer Center, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY 10021, USA.
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Nardone G, Compare D, Rocco A. A microbiota-centric view of diseases of the upper gastrointestinal tract. Lancet Gastroenterol Hepatol 2017; 2:298-312. [PMID: 28404159 DOI: 10.1016/s2468-1253(16)30108-x] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 08/03/2016] [Accepted: 09/07/2016] [Indexed: 12/13/2022]
Abstract
The distinctive anatomy and physiology of the upper gastrointestinal tract and the difficulty of obtaining samples led to the theory that it was bacteria free. However, multiomics studies are indicating otherwise. Although influenced by both oral and gastric bacteria, the resident microbial ecosystem in the oesophagus is dominated by Streptococcus. A shift from Gram-positive to Gram-negative bacteria occurs in oesophagitis and Barrett's oesophagus, and this shift might be involved in the pathogenesis of oesophageal adenocarcinoma. The gastric microenvironment is populated by microbial communities mainly of the Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria phyla and species of the Lactobacillus, Streptococcus, and Propionibacterium genera. The composition of gastric microbiota is highly dynamic, and is influenced by acid suppression, gastric inflammation, and Helicobacter pylori. Duodenal microbes are also implicated in the onset and outcome of coeliac disease. Bacteria of the genera Bacteroides, Clostridium, and Staphylococcus dominate the duodenal flora in active coeliac disease whereas lactobacilli and bifidobacteria decrease. Although knowledge of the composition of the microbiota of the upper gastrointestinal tract has advanced substantially, this information is far from being translated to the clinical setting. In this Review, we assess the data related to the potential contribution of microbes to the susceptibility for and pathogenesis of upper gastrointestinal diseases.
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Affiliation(s)
- Gerardo Nardone
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University Federico II of Naples, Naples, Italy
| | - Debora Compare
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University Federico II of Naples, Naples, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University Federico II of Naples, Naples, Italy
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Abstract
The esophagus and stomach are host to their own population of bacteria, which differs in health and disease. Helicobacter pylori uniquely colonizes only gastric mucosa, but an increasing number of bacteria is now isolated from the gastric juice and gastric mucosa, including Lactobacillus. The presence of H pylori alters populations of other gastric bacteria with a marked reduction in diversity. Alterations in intragastric acidity may be the cause or the consequence of changes in the microbial populations of the stomach. Esophageal inflammation is associated with an altered microbiota in gastroesophageal reflux disease, Barrett's esophagus, eosinophilic esophagitis, and cancer.
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48
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49
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Sonnenberg A, Turner KO, Spechler SJ, Genta RM. The influence of Helicobacter pylori on the ethnic distribution of Barrett's metaplasia. Aliment Pharmacol Ther 2017; 45:283-290. [PMID: 27862104 DOI: 10.1111/apt.13854] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 09/20/2016] [Accepted: 10/13/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Environmental risk factors associated with ethnicity may contribute to the occurrence of Barrett's metaplasia. AIM To investigate the interaction between ethnicity and Helicobacter pylori infection in the occurrence of Barrett's metaplasia among patients undergoing oesophago-gastro-duodenoscopy. METHODS The Miraca Life Sciences Database is an electronic repository of histopathological patient records. A case-control study evaluated the influence of age, gender, ethnicity and histological diagnosis of H. pylori on the occurrence of Barrett's metaplasia. RESULTS The total study population comprised 596 479 subjects, of whom 76 475 harboured a diagnosis of Barrett's metaplasia. Male sex, age and H. pylori infection in declining order exerted the strongest influence on the occurrence of BM. In comparison with the population comprising Caucasians and African Americans, Barrett's metaplasia was less common among subjects of African (OR = 0.09, 95% CI = 0.01-0.43), Middle Eastern (0.26, 0.20-0.34), East Asian (0.35, 0.31-0.40), Indian (0.39, 0.32-0.47), Hispanic (0.62, 0.59-0.64) or Jewish descent (0.50, 0.45-0.54), but more common among subjects of Northern European descent (1.14, 1.03-1.26). With the exception of Jews and Northern Europeans, all other ethnic subgroups were characterised by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of Barrett's metaplasia (R2 = 0.82, P < 0.001), as well as dysplasia or oesophageal adenocarcinoma (R2 = 0.81, P < 0.001). CONCLUSION Our analysis reveals an inverse relationship between the prevalence of Barrett's metaplasia and H. pylori gastritis among different ethnic groups within the United States.
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Affiliation(s)
- A Sonnenberg
- Miraca Life Sciences, Irving, TX, USA.,Oregon Health & Science University, Portland, OR, USA
| | | | - S J Spechler
- VA North Texas Health Care System, Dallas, TX, USA
| | - R M Genta
- Miraca Life Sciences, Irving, TX, USA.,Baylor College of Medicine, Houston, TX, USA
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Peña J, Rojas H, Reyes N, Fernández-Delgado M, García-Amado MA, Michelangeli F, Contreras M. Multiple cag genotypes of Helicobacter pylori isolates colonize the oesophagus in individual hosts in a Venezuelan population. J Med Microbiol 2016; 66:226-235. [PMID: 27983473 DOI: 10.1099/jmm.0.000409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Multiple Helicobacter pylori strains colonize and coexist in the stomach of one single patient, carrying heterogeneous distributions of cag genotypes. The oesophagus provides a niche for H. pylori colonization; however, little is known about its adaptive role. METHODOLOGY Using PCR for cagA, cagE and virB11 genes from cag-pathogenicity island (PAI) and Etest for antimicrobial susceptibility test, we determined cag-PAI genotypes associated with H. pylori virulence, when positive cultures were matching in both the stomach and the oesophagus (96 isolates; 8 out of 80 dyspeptic patients). RESULTS The stomach showed complete cag-PAI islands in 77 % of the isolates, whereas the oesophagus showed complete cag-PAI islands only in 44 % of the isolates. Expression of CagA and interleukin 8 correlated with inflammatory processes and histopathological changes in the stomach, but not in the oesophagus. Different cag-PAI profiles were found in both mucosae of an individual host, and at least one oesophagus profile corresponded to one profile identified in stomach. The antibiotic resistance profiles showed variability in the colonization by single or mixed H. pylori isolates in the gastric and oesophageal mucosa both intra- and inter-individuals. CONCLUSION These results demonstrate colonization with multiple H. pylori isolates in the oesophageal mucosa, like those found in the stomach of individual hosts. H. pylori was characterized by a dominant partial island, low interleukin 8 induction with lower histopathological damage and lower antibiotic resistance, suggesting that the microenvironmental changes in individual hosts select less virulent isolates in the oesophagus than in the stomach. New approaches to ensure effective eradication therapy in multi-resistant H. pylori strains must be developed.
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Affiliation(s)
- Jessy Peña
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - Héctor Rojas
- Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.,Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - Nelson Reyes
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - Milagro Fernández-Delgado
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - María-Alexandra García-Amado
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - Fabián Michelangeli
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
| | - Monica Contreras
- Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Miranda, Venezuela
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