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Zhong L, Yang Q, Shao Y, Hu S, Guo L. Helicobacter pylori promotes intestinal flora imbalance and hepatic metabolic disorders under arsenic stress. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 290:117512. [PMID: 39671763 DOI: 10.1016/j.ecoenv.2024.117512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/21/2024] [Accepted: 12/08/2024] [Indexed: 12/15/2024]
Abstract
Environmental arsenic contamination is a serious issue that cannot be ignored, since arsenic levels in drinking water frequently exceed safety standards, and there is an increased prevalence of Helicobacter pylori (H. pylori) infection. This results in an increasing population at risk of simultaneous exposure to both harmful agents, yet whether a synergistic interaction exists between them remains unclear. Therefore, this study aims to investigate the combined effects and underlying pathogenic mechanisms of concurrent exposure to these two hazardous factors by establishing a mouse model that is infected with H. pylori and exposed to inorganic arsenic through drinking water. Analysis of intestinal flora revealed significant alterations in the composition, relative abundance (Akkermansia, Faecalibaculum, Ilieibacterium, etc.), and metabolic potential of the intestinal microflora (amino acid metabolism and energy metabolism) in the combinatory exposure group. Non-targeted metabolomics analysis identified that the combinatory exposure group exhibited greater fluctuations in metabolite content, particularly in triacylglycerol, fatty-acid, peptide and amino acid. Moreover, H. pylori infection and arsenic exposure had increased levels of metabolites associated with the intestinal microbiota in their livers (4-Ethylphenyl sulfate and Phenylacetylglycine). Further analysis revealed significant correlations between changes in the intestinal flora and alterations in liver metabolic profiles. Herein, we hypothesize that H. pylori infection may exacerbate the intestinal flora imbalance and hepatic metabolic disturbances caused by arsenic exposure, which may disrupt enterohepatic homeostasis and potentially increase biological susceptibility to heavy metal toxicity.
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Affiliation(s)
- Linmin Zhong
- Dongguan Key Laboratory of Public Health Laboratory Science, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Qiling Yang
- Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Yiming Shao
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
| | - Shanwen Hu
- Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Lianxian Guo
- Dongguan Key Laboratory of Public Health Laboratory Science, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
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2
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Li Y, He C, Lu N. Impacts of Helicobacter pylori infection and eradication on gastrointestinal microbiota: An up-to-date critical review and future perspectives. Chin Med J (Engl) 2024; 137:2833-2842. [PMID: 39501846 DOI: 10.1097/cm9.0000000000003348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Indexed: 12/17/2024] Open
Abstract
ABSTRACT Helicobacter pylori ( H. pylori ) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori -associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori may provide potential targets for H. pylori -related gastric diseases and extragastric manifestations.
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Affiliation(s)
- Yu Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China
- HuanKui Academy, Nanchang University, Nanchang, Jiangxi 330006, China
| | - Cong He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China
| | - Nonghua Lu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China
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3
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Barakat S, Abdel-Fadeel M, Sharaki O, Shafei ME, Elbanna B, Mahfouz A. Is Helicobacter pylori infection a risk factor for non-alcoholic fatty liver disease in children? Eur J Pediatr 2024; 184:47. [PMID: 39601920 PMCID: PMC11602778 DOI: 10.1007/s00431-024-05867-y] [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: 08/29/2024] [Revised: 10/25/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024]
Abstract
Helicobacter pylori infection has been investigated as a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Some studies suggest a possible link between the two conditions. The purpose of this study is to study the relationship between H. pylori infection and NAFLD in pediatrics and its relation to NAFLD grades. A case-control study to identify predictors of NAFLD and a comparative cross-sectional approach to determine factors affecting NAFLD grades were adopted. One hundred NAFLD children (ultrasound-based) and a control group of 100 non-NAFLD children were recruited. Both groups were evaluated by detecting H. pylori stool antigen. Immunoglobulin G antibodies to Cag A (cytotoxin-associated gene A), Vac A (vacuolating cytotoxin A), Gro EL (chaperonin Gro EL), HCPC (Helicobacter cysteine-rich protein C), and Ure A (Urease subunit A) were assessed in the serum of those with positive stool antigen. H. pylori infection was significantly higher in NAFLD children compared to the control group (64% versus 25%, p-value < .001). (NAFLD children showed higher Cag A and Vac A positivity (34, 10%) versus (2%, 0%) in the control group, respectively, p-value < .001). The regression model showed that H. pylori positivity (OR (odds ratio) = 5.021, 95% CI (confidence interval): 1.105-22.815), homeostatic model assessment of insulin resistance (Homa IR) (OR = 18.840, 95% CI: 3.998-88.789), waist percentile (OR = 1.184, 95% CI: 1.044-1.344), and triglycerides (OR = 1.029, 95% CI: 1.012-1.047) were predictors for NAFLD. Cag A positivity (OR = 2.740, 95% CI: 1.013-7.411) was associated with higher NAFLD grade (grade 2 fatty liver). CONCLUSIONS H. pylori infection could increase the risk of NAFLD in children. Triglycerides, waist circumference, and Homa IR are significant independent predictors of NAFLD. WHAT IS KNOWN • NAFLD has become one of the most common liver diseases among children because of the increased prevalence of pediatric obesity. • Dyslipidemia and insulin resistance play a central role in NAFLD pathogenesis. • NAFLD could be explained by the multiple-hit hypothesis. The gut microbiota is an important factor in this hypothesis (gut liver axis). WHAT IS NEW • Helicobacter pylori infection could increase the risk of NAFLD in children. • H. pylori Cytotoxin-associated gene A (Cag A) positivity is associated with higher NAFLD grade.
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Affiliation(s)
- Sana Barakat
- Paediatric Department, Faculty of Medicine, Alexandria University, Champollion Street El-Khartoum Square, Azarita Medical Campus 21311, Alexandria, Egypt
| | - Mohamed Abdel-Fadeel
- Paediatric Department, Faculty of Medicine, Alexandria University, Champollion Street El-Khartoum Square, Azarita Medical Campus 21311, Alexandria, Egypt
| | - Ola Sharaki
- Clinical and Chemical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mohamed El Shafei
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Basant Elbanna
- Paediatric Department, Faculty of Medicine, Alexandria University, Champollion Street El-Khartoum Square, Azarita Medical Campus 21311, Alexandria, Egypt.
| | - Aml Mahfouz
- Paediatric Department, Faculty of Medicine, Alexandria University, Champollion Street El-Khartoum Square, Azarita Medical Campus 21311, Alexandria, Egypt
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4
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Ignatiou A, Pitsouli C. Host-diet-microbiota interplay in intestinal nutrition and health. FEBS Lett 2024; 598:2482-2517. [PMID: 38946050 DOI: 10.1002/1873-3468.14966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 06/11/2024] [Indexed: 07/02/2024]
Abstract
The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.
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Affiliation(s)
- Anastasia Ignatiou
- Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus
| | - Chrysoula Pitsouli
- Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus
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Rowaiye A, Ibeanu GC, Bur D, Nnadi S, Mgbeke OE, Morikwe U. Gut microbiota alteration - Cancer relationships and synbiotic roles in cancer therapies. THE MICROBE 2024; 4:100096. [DOI: 10.1016/j.microb.2024.100096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Marashi A, Hasany S, Moghimi S, Kiani R, Mehran Asl S, Dareghlou YA, Lorestani P, Varmazyar S, Jafari F, Ataeian S, Naghavi K, Sajjadi SM, Haratian N, Alinezhad A, Azhdarimoghaddam A, Sadat Rafiei SK, Anar MA. Targeting gut-microbiota for gastric cancer treatment: a systematic review. Front Med (Lausanne) 2024; 11:1412709. [PMID: 39170038 PMCID: PMC11337614 DOI: 10.3389/fmed.2024.1412709] [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: 04/05/2024] [Accepted: 07/17/2024] [Indexed: 08/23/2024] Open
Abstract
Background Preclinical research has identified the mechanisms via which bacteria influence cancer treatment outcomes. Clinical studies have demonstrated the potential to modify the microbiome in cancer treatment. Herein, we systematically analyze how gut microorganisms interact with chemotherapy and immune checkpoint inhibitors, specifically focusing on how gut bacteria affect the pharmacokinetics and pharmacodynamics of cancer treatment. Method This study searched Web of Science, Scopus, and PubMed until August 2023. Studies were screened by their title and abstract using the Rayyan intelligent tool for systematic reviews. Quality assessment of studies was done using the JBI critical appraisal tool. Result Alterations in the gut microbiome are associated with gastric cancer and precancerous lesions. These alterations include reduced microbial alpha diversity, increased bacterial overgrowth, and decreased richness and evenness of gastric bacteria. Helicobacter pylori infection is associated with reduced richness and evenness of gastric bacteria, while eradication only partially restores microbial diversity. The gut microbiome also affects the response to cancer treatments, with higher abundances of Lactobacillus associated with better response to anti-PD-1/PD-L1 immunotherapy and more prolonged progression-free survival. Antibiotic-induced gut microbiota dysbiosis can reduce the anti-tumor efficacy of 5-Fluorouracil treatment, while probiotics did not significantly enhance it. A probiotic combination containing Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus can reduce inflammation, enhance immunity, and restore a healthier gut microbial balance in gastric cancer patients after partial gastrectomy. Conclusion Probiotics and targeted interventions to modulate the gut microbiome have shown promising results in cancer prevention and treatment efficacy.Systematic review registration: https://osf.io/6vcjp.
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Affiliation(s)
- Amir Marashi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Saina Hasany
- Student Research Committee, Islamic Azad University Tehran Medical Sciences, Tehran, Iran
| | - Sadra Moghimi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Kiani
- Student Research Committee, Islamic Azad University Tehran Medical Sciences, Mashhad, Iran
| | - Sina Mehran Asl
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Student Research Committee, Islamic Azad University Tehran Medical Sciences, Tehran, Iran
| | | | - Parsa Lorestani
- School of Medicine, Shahroud Azad University of Medical Sciences, Shahroud, Iran
| | - Shirin Varmazyar
- Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Alborz, Iran
| | - Fatemeh Jafari
- School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Shakiba Ataeian
- School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Kiana Naghavi
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Negar Haratian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arman Alinezhad
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | - Mahsa Asadi Anar
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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7
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Liu Y, Yang DQ, Jiang JN, Jiao Y. Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer. World J Gastrointest Surg 2024; 16:1008-1016. [PMID: 38690050 PMCID: PMC11056658 DOI: 10.4240/wjgs.v16.i4.1008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/01/2024] [Accepted: 03/13/2024] [Indexed: 04/22/2024] Open
Abstract
Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.
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Affiliation(s)
- Ying Liu
- Department of General Surgery, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
| | - Ding-Quan Yang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Jun-Nan Jiang
- Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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8
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Tran SC, Bryant KN, Cover TL. The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk. Gut Microbes 2024; 16:2314201. [PMID: 38391242 PMCID: PMC10896142 DOI: 10.1080/19490976.2024.2314201] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
Helicobacter pylori strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cag pathogenicity island (cag PAI). Colonization of the human stomach with cag PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cag PAI-negative strains. The cag PAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which H. pylori strains containing the cag PAI promote the development of gastric cancer and peptic ulcer disease.
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Affiliation(s)
- Sirena C. Tran
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kaeli N. Bryant
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Timothy L. Cover
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
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9
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Feilstrecker Balani G, dos Santos Cortez M, Picasky da Silveira Freitas JE, Freire de Melo F, Zarpelon-Schutz AC, Teixeira KN. Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection. World J Gastroenterol 2023; 29:4604-4615. [PMID: 37662864 PMCID: PMC10472898 DOI: 10.3748/wjg.v29.i30.4604] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/01/2023] [Accepted: 07/24/2023] [Indexed: 08/10/2023] Open
Abstract
Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.
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Affiliation(s)
| | | | | | - Fabrício Freire de Melo
- Campus Anísio Teixeira, Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Ana Carla Zarpelon-Schutz
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa de Pós-graduação em Biotecnologia - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
| | - Kádima Nayara Teixeira
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
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Fiorani M, Tohumcu E, Del Vecchio LE, Porcari S, Cammarota G, Gasbarrini A, Ianiro G. The Influence of Helicobacter pylori on Human Gastric and Gut Microbiota. Antibiotics (Basel) 2023; 12:765. [PMID: 37107126 PMCID: PMC10135037 DOI: 10.3390/antibiotics12040765] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected by H. pylori colonization, with consequent effects on the gastrointestinal microbiota, exerted via the regulation of various factors, including gastric acidity, host immune responses, antimicrobial peptides, and virulence factors. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Notably, therapy regimens integrated with probiotics have been shown to reduce the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. In light of the deep impact of gut microbiota alterations on human health, the present article aims to provide an overview of the complex interaction between H. pylori and the gastrointestinal microbiota, focusing also on the consequences of eradication therapies and the effects of probiotic supplementation.
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Affiliation(s)
- Marcello Fiorani
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Ege Tohumcu
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Livio Enrico Del Vecchio
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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11
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Rogers AP, Mileto SJ, Lyras D. Impact of enteric bacterial infections at and beyond the epithelial barrier. Nat Rev Microbiol 2023; 21:260-274. [PMID: 36175770 DOI: 10.1038/s41579-022-00794-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2022] [Indexed: 11/09/2022]
Abstract
The mucosal lining of the gut has co-evolved with a diverse microbiota over millions of years, leading to the development of specialized mechanisms to actively limit the invasion of pathogens. However, some enteric microorganisms have adapted against these measures, developing ways to hijack or overcome epithelial micro-integrity mechanisms. This breach of the gut barrier not only enables the leakage of host factors out of circulation but can also initiate a cascade of detrimental systemic events as microbiota, pathogens and their affiliated secretions passively leak into extra-intestinal sites. Under normal circumstances, gut damage is rapidly repaired by intestinal stem cells. However, with substantial and deep perturbation to the gut lining and the systemic dissemination of gut contents, we now know that some enteric infections can cause the impairment of host regenerative processes. Although these local and systemic aspects of enteric disease are often studied in isolation, they heavily impact one another. In this Review, by examining the journey of enteric infections from initial establishment to systemic sequelae and how, or if, the host can successfully repair damage, we will tie together these complex interactions to provide a holistic overview of the impact of enteric infections at and beyond the epithelial barrier.
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Affiliation(s)
- Ashleigh P Rogers
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.,Department of Microbiology, Monash University, Melbourne, Victoria, Australia
| | - Steven J Mileto
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.,Department of Microbiology, Monash University, Melbourne, Victoria, Australia
| | - Dena Lyras
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia. .,Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
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12
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Xu G, Ma S, Dong L, Mendez-Sanchez N, Li H, Qi X. Relationship of Helicobacter pylori Infection with Nonalcoholic Fatty Liver Disease: A Meta-Analysis. Can J Gastroenterol Hepatol 2023; 2023:5521239. [PMID: 36742347 PMCID: PMC9891807 DOI: 10.1155/2023/5521239] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/17/2022] [Accepted: 12/24/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND AND AIMS Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) have become increasingly recognized, both of which affect human health globally. The association of H. pylori infection with NAFLD remains unclear. METHODS PubMed, EMBASE, and Cochrane Library databases were searched. Only a random-effects model was used. Odds ratios (ORs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for the combined estimates of raw data. Adjusted ORs (aORs) and hazard ratios (aHRs) with 95% CIs were calculated for the combined estimates of data adjusted for confounders. RESULTS Thirty-four studies with 218573 participants were included. Based on unadjusted data from 26 cross-sectional studies and 3 case-control studies, H. pylori infection was significantly associated with the presence of NAFLD (OR = 1.26, 95% CI = 1.17-1.36, P < 0.001). Based on adjusted data from 15 cross-sectional studies and 1 case-control study, H. pylori infection was significantly associated with the presence of NAFLD (aOR = 1.25, 95% CI = 1.08-1.44, P < 0.001). Compared with control subjects without NAFLD, patients with moderate (OR = 1.67, 95% CI = 1.17-2.39, P = 0.005) and severe (OR = 1.71, 95% CI = 1.30-2.24, P < 0.001) NAFLD, but not those with mild NAFLD (OR = 1.14, 95% CI = 0.9-1.45, P = 0.286), had significantly higher proportions of H. pylori infection. The association of H. pylori infection with the occurrence of NAFLD was statistically significant based on adjusted data from 3 cohort studies (aHR = 1.18, 95% CI = 1.05-1.34, P = 0.007), but not based on unadjusted data from 3 cohort studies (RR = 1.41, 95% CI = 0.80-2.48, P = 0.237). CONCLUSION H. pylori infection is associated with NAFLD, especially moderate and severe NAFLD. The impact of H. pylori eradication on the prevention of NAFLD should be further explored.
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Affiliation(s)
- Guangqin Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Postgraduate College, Dalian Medical University, Dalian 116044, China
| | - Shaoze Ma
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Postgraduate College, Dalian Medical University, Dalian 116044, China
| | - Liyan Dong
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Postgraduate College, China Medical University, Shenyang 110122, China
| | - Nahum Mendez-Sanchez
- Liver Research Unit, Medica Sur Clinic & Foundation, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Postgraduate College, Dalian Medical University, Dalian 116044, China
- Postgraduate College, China Medical University, Shenyang 110122, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Postgraduate College, Dalian Medical University, Dalian 116044, China
- Postgraduate College, China Medical University, Shenyang 110122, China
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13
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Banse AV, VanBeuge S, Smith TJ, Logan SL, Guillemin K. Secreted Aeromonas GlcNAc binding protein GbpA stimulates epithelial cell proliferation in the zebrafish intestine. Gut Microbes 2023; 15:2183686. [PMID: 36859771 PMCID: PMC9988336 DOI: 10.1080/19490976.2023.2183686] [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: 08/30/2022] [Revised: 12/19/2022] [Accepted: 02/16/2023] [Indexed: 03/03/2023] Open
Abstract
In response to microbiota colonization, the intestinal epithelia of many animals exhibit increased rates of cell proliferation. We used gnotobiotic larval zebrafish to identify a secreted factor from the mutualist Aeromonas veronii that is sufficient to promote intestinal epithelial cell proliferation. This secreted A. veronii protein is a homologue of the Vibrio cholerae GlcNAc binding protein GbpA, which was identified as a chitin-binding colonization factor in mice. GbpA was subsequently shown to be a lytic polysaccharide monooxygenase (LPMO) that can degrade recalcitrant chitin. Our phenotypic characterization of gbpA deficient A. veronii found no alterations in these cells' biogeography in the zebrafish intestine and only a modest competitive disadvantage in chitin-binding and colonization fitness when competed against the wild-type strain. These results argue against the model of GbpA being a secreted adhesin that binds simultaneously to bacterial cells and GlcNAc, and instead suggests that GbpA is part of a bacterial GlcNAc utilization program. We show that the host proliferative response to GbpA occurs in the absence of bacteria upon exposure of germ-free zebrafish to preparations of native GbpA secreted from either A. veronii or V. cholerae or recombinant A. veronii GbpA. Furthermore, domain 1 of A. veronii GbpA, containing the predicted LPMO activity, is sufficient to stimulate intestinal epithelial proliferation. We propose that intestinal epithelial tissues upregulate their rates of renewal in response to secreted bacterial GbpA proteins as an adaptive strategy for coexisting with bacteria that can degrade glycan constituents of the protective intestinal lining.
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Affiliation(s)
- Allison V. Banse
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA
| | - Stephanie VanBeuge
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA
| | - T. Jarrod Smith
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA
| | | | - Karen Guillemin
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada
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14
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Dewayani A, Afrida Fauzia K, Alfaray RI, Waskito LA, Doohan D, Rejeki PS, Alshawsh MA, Rezkitha YAA, Yamaoka Y, Miftahussurur M. Gastric microbiome changes in relation with Helicobacter pylori resistance. PLoS One 2023; 18:e0284958. [PMID: 37200323 DOI: 10.1371/journal.pone.0284958] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 04/12/2023] [Indexed: 05/20/2023] Open
Abstract
INTRODUCTION Inadequate antimicrobial treatment has led to multidrug-resistant (MDR) bacteria, including Helicobacter pylori (H. pylori), which one of the notable pathogens in the stomach. Antibiotic-induced changes in the microbiota can negatively affect the host. This study aimed to determine the influence of H. pylori resistance on the diversity and abundance of the stomach microbiome. METHODS Bacterial DNA was extracted from biopsy samples of patients presenting dyspepsia symptoms with H. pylori positive from cultures and histology. DNA was amplified from the V3-V4 regions of the 16S rRNA gene. In-vitro E-test was used to detect antibiotic resistance. Microbiome community analysis was conducted through α-diversity, β-diversity, and relative abundance. RESULTS Sixty-nine H. pylori positive samples were eligible after quality filtering. Following resistance status to five antibiotics, samples were classified into 24 sensitive, 24 single resistance, 16 double resistance, 5 triple resistance. Samples were mostly resistant to metronidazole (73.33%; 33/45). Comparation of four groups displayed significantly elevated α-diversity parameters under the multidrug resistance condition (all P <0.05). A notable change was observed in triple-resistant compared to sensitive (P <0.05) and double-resistant (P <0.05) groups. Differences in β-diversity by UniFrac and Jaccard were not significant in terms of the resistance (P = 0.113 and P = 0.275, respectively). In the triple-resistant group, the relative abundance of Helicobacter genera was lower, whereas that of Streptococcus increased. Moreover, the linear discriminant analysis effect size (LEfSe) was associated with the presence of Corynebacterium and Saccharimonadales in the single-resistant group and Pseudomonas and Cloacibacterium in the triple-resistant group. CONCLUSION Our results suggest that the resistant samples showed a higher trend of diversity and evenness than the sensitive samples. The abundance of H. pylori in the triple-resistant samples decreased with increasing cohabitation of pathogenic bacteria, which may support antimicrobial resistance. However, antibiotic susceptibility determined by the E-test may not completely represent the resistance status.
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Affiliation(s)
- Astri Dewayani
- Oita University Faculty of Medicine, Department of Infectious Disease Control, Yufu, Oita, Japan
- Faculty of Medicine, Department of Anatomy, Histology and Pharmacology, Universitas Airlangga, Surabaya, Indonesia
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
| | - Kartika Afrida Fauzia
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
- Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine, Yufu, Oita, Japan
- Faculty of Medicine, Department of Public Health and Preventive Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ricky Indra Alfaray
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
- Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine, Yufu, Oita, Japan
| | - Langgeng Agung Waskito
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
- Faculty of Medicine, Department of Medical Physiology and Biochemistry, Universitas Airlangga, Surabaya, Indonesia
| | - Dalla Doohan
- Faculty of Medicine, Department of Anatomy, Histology and Pharmacology, Universitas Airlangga, Surabaya, Indonesia
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
| | - Purwo Sri Rejeki
- Faculty of Medicine, Department of Medical Physiology and Biochemistry, Universitas Airlangga, Surabaya, Indonesia
| | - Mohammed Abdullah Alshawsh
- Faculty of Medicine, Department of Pharmacology, Universiti Malaya, Kuala Lumpur, Malaysia
- Faculty of Medicine, School of Clinical Sciences, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
- Faculty of Medicine, Department of Internal Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Yoshio Yamaoka
- Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine, Yufu, Oita, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, United States of America
- Research Center for Global and Local Infectious Diseases, Oita University, Yufu, Oita, Japan
- Faculty of Medicine, Department of Internal Medicine, Division of Gastroentero-Hepatology, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Institute of Tropical Disease, Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, Indonesia
- Faculty of Medicine, Department of Internal Medicine, Division of Gastroentero-Hepatology, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
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15
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Cui MY, Cui ZY, Zhao MQ, Zhang MJ, Jiang QL, Wang JJ, Lu LG, Lu YY. The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota. BMC Microbiol 2022; 22:321. [PMID: 36581836 PMCID: PMC9798553 DOI: 10.1186/s12866-022-02732-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 12/12/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.
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Affiliation(s)
- Meng-Yan Cui
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Zhen-Yu Cui
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Meng-Qi Zhao
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Meng-Jie Zhang
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Qiao-Li Jiang
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Jing-Jing Wang
- grid.412478.c0000 0004 1760 4628Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Lun-Gen Lu
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Ying-Ying Lu
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China ,grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
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16
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Burcher KM, Burcher JT, Inscore L, Bloomer CH, Furdui CM, Porosnicu M. A Review of the Role of Oral Microbiome in the Development, Detection, and Management of Head and Neck Squamous Cell Cancers. Cancers (Basel) 2022; 14:4116. [PMID: 36077651 PMCID: PMC9454796 DOI: 10.3390/cancers14174116] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
The role of the microbiome in the development and propagation of head and neck squamous cell cancer (HNSCC) is largely unknown and the surrounding knowledge lags behind what has been discovered related to the microbiome and other malignancies. In this review, the authors performed a structured analysis of the available literature from several databases. The authors discuss the merits and detriments of several studies discussing the microbiome of the structures of the aerodigestive system throughout the development of HNSCC, the role of the microbiome in the development of malignancies (generally and in HNSCC) and clinical applications of the microbiome in HNSCC. Further studies will be needed to adequately describe the relationship between HNSCC and the microbiome, and to push this relationship into a space where it is clinically relevant outside of a research environment.
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Affiliation(s)
| | | | - Logan Inscore
- Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
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17
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Chen X, Wang N, Wang J, Liao B, Cheng L, Ren B. The interactions between oral-gut axis microbiota and Helicobacter pylori. Front Cell Infect Microbiol 2022; 12:914418. [PMID: 35992177 PMCID: PMC9381925 DOI: 10.3389/fcimb.2022.914418] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
In the human body, each microbial habitat exhibits a different microbial population pattern, and these distinctive microflorae are highly related to the development of diseases. The microbial interactions from host different niches are becoming crucial regulators to shape the microbiota and their physiological or pathological functions. The oral cavity and gut are the most complex and interdependent microbial habitats. Helicobacter pylori is one of the most important pathogens from digestive tract, especially the stomach, due to its direct relationships with many gastric diseases including gastric cancer. H. pylori infections can destroy the normal gastric environment and make the stomach a livable channel to enhance the microbial interactions between oral cavity and gut, thus reshaping the oral and gut microbiomes. H. pylori can be also detected in the oral and gut, while the interaction between the oral-gut axis microbiota and H. pylori plays a major role in H. pylori’s colonization, infection, and pathogenicity. Both the infection and eradication of H. pylori and its interaction with oral-gut axis microbiota can alter the balance of the microecology of the oral-gut axis, which can affect the occurrence and progress of related diseases. The shift of oral-gut axis microbiota and their interactions with H. pylori maybe potential targets for H. pylori infectious diagnosis and treatment.
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Affiliation(s)
- Xi Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Nanxi Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Jiannan Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Binyou Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Lei Cheng, ; Biao Ren,
| | - Biao Ren
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Lei Cheng, ; Biao Ren,
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18
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Effect of Probiotic-Assisted Eradication of cagA+/vacA s1m1 Helicobacter pylori on Intestinal Flora. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8607671. [PMID: 35528160 PMCID: PMC9076325 DOI: 10.1155/2022/8607671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/10/2022] [Accepted: 04/15/2022] [Indexed: 12/14/2022]
Abstract
Objective. We attempted to evaluate the effects of probiotic-assisted eradication of cytotoxin-associated gene A (cagA)+/vacuolating cytotoxin A (vacA) s1m1 Helicobacter pylori (H. pylori) on the intestinal flora, inflammatory factors, and clinical outcomes. Methods. A total of 180 patients with cagA+/vacA s1m1 H. pylori were randomly divided into two groups. Group A was treated with bismuth quadruple therapy (BQT). Group B was treated with S. boulardii in addition to BQT. The distribution of intestinal flora, serum interleukin-8 (IL-8), IL-17, tumor necrosis factor-α (TNF-α) levels, recovery time of clinical symptoms, total effective rate of clinical symptoms, H. pylori eradication rate, and adverse reactions were observed. Results. 2 weeks after treatment, the contents of Bifidobacterium, Bacteroides, and Lactobacillus in the intestinal tract of Group A decreased, while the amounts of Enterococcus and Enterobacter increased. In Group B, the contents of Bifidobacterium, Bacteroides, and Lactobacillus increased, while the amounts of Enterococcus and Enterobacter did not change significantly. Moreover, the trend of this flora change was still present at 4 weeks after treatment. Compared with Group A, Group B had lower IL-8, IL-17, and TNF-α levels, shorter recovery time of clinical symptoms, higher overall efficiency of clinical symptoms, and lower occurrence of adverse reactions. The eradication rate did not differ significantly between the two groups. Conclusion. BQT can lead to intestinal flora disorders in cagA+/vacA s1m1 H. pylori patients. S. boulardii can improve the distribution of intestinal flora, downregulate immune-inflammatory mediators, and modify clinical symptoms in patients.
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19
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Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol 2022; 13:1347-1363. [PMID: 35124288 PMCID: PMC8933844 DOI: 10.1016/j.jcmgh.2022.01.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 12/30/2022]
Abstract
Gastric cancer (GC) is the fifth most common cancer and the fourth most common cause of cancer-related death worldwide. The intestinal type of GC progresses from acute to chronic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma. Infection of the stomach by Helicobacter pylori, a Gram-negative bacterium that infects approximately 50% of the world's population, is the causal determinant that initiates the gastric inflammation and then disease progression. In this context, the induction of the innate immune response of gastric epithelial cells and myeloid cells by H. pylori effectors plays a critical role in the outcome of the infection. However, only 1% to 3% of infected patients develop gastric adenocarcinoma, emphasizing that other mechanisms regulate the localized non-specific response, including the gastric microbiota and genetic factors. This review summarizes studies describing the factors that induce and regulate the mucosal innate immune response during H. pylori infection.
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Affiliation(s)
- Alain P Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee.
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Nashville, Tennessee; Program in Cancer Biology, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
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20
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Jamali A, Karbalai S, Tefagh G, Jamali R, Ahmadi A. The Effects of Helicobacter Pylori Eradication on Liver Function and Metabolic Profile in Non-diabetic Non-alcoholic Steatohepatitis: A 5-year Randomized Clinical Trial. Middle East J Dig Dis 2022; 14:85-95. [PMID: 36619724 PMCID: PMC9489323 DOI: 10.34172/mejdd.2022.260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 08/07/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND: To evaluate the effects of Helicobacter pylori (HP) eradication on liver function tests (LFT) and fat content (LFC) in non-diabetic non-alcoholic steatohepatitis (NASH). METHODS: This randomized clinical trial included dyspeptic HP infected non-diabetic NASH participants. The intervention arm received HP eradication treatment, while the control arm did not get any HP treatment. In the meantime, the standard management of NASH was performed in both trial arms. Mean alterations in LFT were the primary outcome and the secondary outcomes included the mean changes in LFC and serum metabolic profile. The trial follow-up period was 5 years. RESULTS: 40 participants (female: 20), with a mean age of 41.58 (±12.31) years, were enrolled in the study. The HP eradication arm included 20 participants (female: 11) with a mean age of 40.25 (±10.59) years, and the control arm consisted of 20 individuals (female: 9) with a mean age of 42.90 (±13.97) years. The tests of within-subjects effects showed a significant decrease in mean serum alanine aminotransferase (ALT; P=0.007), triglyceride (TG; P=0.04), cholesterol (P=0.004), and fasting blood sugar (FBS; P<0.001), and an increase in high-density lipoprotein (HDL; P=0.04) in both research groups during the study period. The tests of between-subjects effects demonstrated a more significant decrement of FBS in HP eradicated patients than the controls (P=0.02). The reduction in waist circumference, aspartate aminotransferase (AST), ALT, alkaline phosphatase, triglyceride, cholesterol, low-density lipoprotein, insulin, and LFC were more prominent in the intervention group than the controls; however, these differences were not statistically significant. CONCLUSION: Adding HP eradication treatment to standard NASH treatment showed more therapeutic effect thanthe standard NASH treatment protocol alone regarding the decrement of FBS in participants with dyspeptic non-diabetic NASH. Considering the non-statistically significant improvement in other metabolic indices and LFT in this trial, further studies are recommended.
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Affiliation(s)
- Arsia Jamali
- Department of Internal Medicine, Eisenhower Medical Center, California, USA
| | - Shahrokh Karbalai
- Research Development Center, Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazale Tefagh
- Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Raika Jamali
- Research Development Center, Sina Hospital; Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ayat Ahmadi
- Knowledge Utilization Research Center, Tehran University of Medical Sciences, Tehran, Iran
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21
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Iino C, Shimoyama T. Impact of Helicobacter pylori infection on gut microbiota. World J Gastroenterol 2021; 27:6224-6230. [PMID: 34712028 PMCID: PMC8515792 DOI: 10.3748/wjg.v27.i37.6224] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/13/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.
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Affiliation(s)
- Chikara Iino
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Tadashi Shimoyama
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
- Department of Internal Medicine, Aomori General Health Examination Center, Aomori 030-0962, Japan
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22
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Huang Y, Ding Y, Xu H, Shen C, Chen X, Li C. Effects of sodium butyrate supplementation on inflammation, gut microbiota, and short-chain fatty acids in Helicobacter pylori-infected mice. Helicobacter 2021; 26:e12785. [PMID: 33609322 DOI: 10.1111/hel.12785] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/20/2021] [Accepted: 01/20/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Inflammation induced by Helicobacter pylori (H. pylori) infection is the basis for the pathogenesis of H. pylori. Butyric acid, a diet-related microbial-associated metabolite, is connected to inflammation, metabolic syndrome, and other diseases. Several studies have indicated the effects of sodium butyrate (SB) against bacteria; however, the effects of SB on the main virulence factors of H. pylori, H. pylori-induced inflammation, and gut microbiota composition remain unclear. MATERIALS AND METHODS SB was supplemented in H. pylori coculture and administered to mice infected with H. pylori. The effects of SB intake on inflammation, gut microbiota composition, and short-chain fatty acids (SCFAs) in H. pylori-infected mice were assessed. RESULTS The in vitro experiments demonstrated that SB not only inhibited the growth of H. pylori but also decreased the mRNA expression of CagA and VacA. SB intake reduced the production of virulence factors in H. pylori-infected mice, inhibited the IκBα/NF-κB pathway by reducing the expression of Toll-like receptors (TLRs), and reduced the production of TNF-α and IL-8. Further analysis demonstrated that H. pylori infection altered the relative abundance of the intestinal microbial community in mice. The level of SCFAs in the feces of H. pylori-infected mice was changed, although the intake of SB did not obviously change the level of SCFAs. CONCLUSIONS Our study showed that SB may decrease H. pylori-induced inflammation by inhibiting the viability and virulence of H. pylori and may reduce inflammation in association with the gut microbiota in H. pylori-infected mice. This study may provide novel insights into the mechanisms by which SB, a diet-related microbial-associated metabolite, affects H. pylori-induced disease development.
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Affiliation(s)
- Yumei Huang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yinhuan Ding
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Huiyuan Xu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Cheng Shen
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xia Chen
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Changping Li
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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23
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Harnish JM, Link N, Yamamoto S. Drosophila as a Model for Infectious Diseases. Int J Mol Sci 2021; 22:2724. [PMID: 33800390 PMCID: PMC7962867 DOI: 10.3390/ijms22052724] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/11/2021] [Accepted: 02/14/2021] [Indexed: 12/19/2022] Open
Abstract
The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.
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Affiliation(s)
- J. Michael Harnish
- Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; (J.M.H.); (N.L.)
- Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
| | - Nichole Link
- Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; (J.M.H.); (N.L.)
- Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Howard Hughes Medical Institute, Houston, TX 77030, USA
| | - Shinya Yamamoto
- Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; (J.M.H.); (N.L.)
- Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Department of Neuroscience, BCM, Houston, TX 77030, USA
- Development, Disease Models and Therapeutics Graduate Program, BCM, Houston, TX 77030, USA
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24
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Tao ZH, Han JX, Fang JY. Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota. Helicobacter 2020; 25:e12754. [PMID: 32876377 DOI: 10.1111/hel.12754] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/12/2020] [Accepted: 08/03/2020] [Indexed: 12/16/2022]
Abstract
The rapid development of microbiota research has remolded our view of human physiological and pathological processes. Among all the gastrointestinal microorganisms, Helicobacter pylori (H pylori) is probably the most notorious constituent. Although half of the adults worldwide are infected with H pylori, their clinical manifestations vary widely, suggesting other microorganisms beyond H pylori may play a role in determining clinical outcomes. Recently, many studies have put effort into elucidating the crosstalk within the human microbiota, some of which specifically explored the interplay between H pylori and other gastrointestinal microbial members. In this work, we reviewed these potential interactions. Meanwhile, the impacts of H pylori eradication therapy on gastrointestinal microbial homeostasis were summarized in terms of diversity, composition, functional capacity, and antibiotic resistance.
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Affiliation(s)
- Zhi-Hang Tao
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ji-Xuan Han
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing-Yuan Fang
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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25
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Kamareddine L, Najjar H, Sohail MU, Abdulkader H, Al-Asmakh M. The Microbiota and Gut-Related Disorders: Insights from Animal Models. Cells 2020; 9:cells9112401. [PMID: 33147801 PMCID: PMC7693214 DOI: 10.3390/cells9112401] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 10/23/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023] Open
Abstract
Over the past decade, the scientific committee has called for broadening our horizons in understanding host–microbe interactions and infectious disease progression. Owing to the fact that the human gut harbors trillions of microbes that exhibit various roles including the production of vitamins, absorption of nutrients, pathogen displacement, and development of the host immune system, particular attention has been given to the use of germ-free (GF) animal models in unraveling the effect of the gut microbiota on the physiology and pathophysiology of the host. In this review, we discuss common methods used to generate GF fruit fly, zebrafish, and mice model systems and highlight the use of these GF model organisms in addressing the role of gut-microbiota in gut-related disorders (metabolic diseases, inflammatory bowel disease, and cancer), and in activating host defense mechanisms and amending pathogenic virulence.
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Affiliation(s)
- Layla Kamareddine
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar; (L.K.); (H.N.); (M.U.S.); (H.A.)
| | - Hoda Najjar
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar; (L.K.); (H.N.); (M.U.S.); (H.A.)
| | - Muhammad Umar Sohail
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar; (L.K.); (H.N.); (M.U.S.); (H.A.)
- Biomedical Research Center, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar
| | - Hadil Abdulkader
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar; (L.K.); (H.N.); (M.U.S.); (H.A.)
| | - Maha Al-Asmakh
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar; (L.K.); (H.N.); (M.U.S.); (H.A.)
- Biomedical Research Center, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar
- Correspondence: ; Tel.: +974-4403-4789
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26
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Younes S, Al-Sulaiti A, Nasser EAA, Najjar H, Kamareddine L. Drosophila as a Model Organism in Host-Pathogen Interaction Studies. Front Cell Infect Microbiol 2020; 10:214. [PMID: 32656090 PMCID: PMC7324642 DOI: 10.3389/fcimb.2020.00214] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/20/2020] [Indexed: 12/29/2022] Open
Abstract
Owing to the genetic similarities and conserved pathways between a fruit fly and mammals, the use of the Drosophila model as a platform to unveil novel mechanisms of infection and disease progression has been justified and widely instigated. Gaining proper insight into host-pathogen interactions and identifying chief factors involved in host defense and pathogen virulence in Drosophila serves as a foundation to establish novel strategies for infectious disease prevention and control in higher organisms, including humans.
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Affiliation(s)
- Salma Younes
- Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Asma Al-Sulaiti
- Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | | | - Hoda Najjar
- Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Layla Kamareddine
- Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
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27
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The Helicobacter pylori Cag Type IV Secretion System. Trends Microbiol 2020; 28:682-695. [PMID: 32451226 DOI: 10.1016/j.tim.2020.02.004] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 01/30/2020] [Accepted: 02/25/2020] [Indexed: 12/24/2022]
Abstract
Colonization of the human stomach with Helicobacter pylori strains containing the cag pathogenicity island is a risk factor for development of gastric cancer. The cag pathogenicity island contains genes encoding a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS). The molecular architecture of the H. pylori Cag T4SS is substantially more complex than that of prototype T4SSs in other bacterial species. In this review, we discuss recent discoveries pertaining to the structure and function of the Cag T4SS and its role in gastric cancer pathogenesis.
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28
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Wu D, Cao M, Li N, Zhang A, Yu Z, Cheng J, Xie X, Wang Z, Lu S, Yan S, Zhou J, Peng J, Zhao J. Effect of trimethylamine N-oxide on inflammation and the gut microbiota in Helicobacter pylori-infected mice. Int Immunopharmacol 2019; 81:106026. [PMID: 31759863 DOI: 10.1016/j.intimp.2019.106026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 10/14/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
Diet is one of the factors contributing to symptom of Helicobacter pylori (H. pylori) infection. Trimethylamine N-oxide (TMAO), a diet-related microbial metabolite, is associated with inflammatory and metabolic diseases. The aim of this study is to investigate the effects of TMAO intake on inflammation and gut microbiota composition in H. pylori-infected mice via 16S rRNA sequencing and biochemical analyses. The in vitro experiments showed that TMAO not only increased the expression of growth- and metabolism-associated genes and the urease activity of H. pylori, but increased the production of virulence factors. Moreover, TMAO intake increased the production of inflammatory markers and reduced the richness and diversity of the gut microbiota in H. pylori-infected mice. Further analysis showed that TMAO increased the relative abundance of Escherichia_Shigella in H. pylori-infected mice, which had positive correlation with the levels of LPS, CRP, and CXCL1. Collectively, our results suggest that TMAO may aggravate H. pylori-induced inflammation by increasing the viability and virulence of H. pylori and may aggravate inflammation in association with the gut microbiota in H. pylori-infected mice. This study may provide a novel insight into the mechanism for the effect of diet-derived metabolites such as TMAO on H. pylori-induced disease development.
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Affiliation(s)
- Daoyan Wu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China; Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China
| | - Mei Cao
- Core Laboratory, School of Medicine, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu 610072, PR China
| | - Ningzhe Li
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Andong Zhang
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Zhihao Yu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Juan Cheng
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Xiulan Xie
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Zeyu Wang
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Shaofei Lu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Shiying Yan
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Jie Zhou
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Jingshan Peng
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Jian Zhao
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
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29
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Classification of Helicobacter pylori Virulence Factors: Is CagA a Toxin or Not? Trends Microbiol 2019; 27:731-738. [DOI: 10.1016/j.tim.2019.04.010] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/16/2019] [Accepted: 04/26/2019] [Indexed: 12/20/2022]
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30
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Mentis AFA, Boziki M, Grigoriadis N, Papavassiliou AG. Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword. Cell Mol Life Sci 2019; 76:2477-2486. [PMID: 30783683 PMCID: PMC11105440 DOI: 10.1007/s00018-019-03044-1] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 02/08/2019] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori (H. pylori) infection affects an estimated 4.4 billion people globally. Moreover, H. pylori presents the most significant risk factor for gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and it is the first example of bacterial infection linked to carcinogenesis. Here, we contend that H. pylori research, which focuses on a cancer-causing pathogen resident in a relatively accessible organ, the stomach, could constitute an exemplar for microbial-related carcinogenesis in less tractable organs, such as the pancreas and lung. In this context, molecular biological approaches that could reap rewards are reviewed, including: (1) gastric cancer dynamics, particularly the role of stem cells and the heterogeneity of neoplastic cells, which are currently being investigated at the single-cell sequencing level; (2) mechanobiology, and the role of three-dimensional organoids and matrix metalloproteases; and (3) the connection between H. pylori and host pathophysiology and the gut microbiome. In the context of H. pylori's contribution to gastric cancer, several important conundrums remain to be fully elucidated. From among them, this article discusses (1) why H. pylori infection, which causes both gastric and duodenal inflammation, is only linked to gastric cancer; (2) whether a "precision oncomicrobiology" approach could enable a fine-tuning of the expression of only cancer-implicated H. pylori genes while maintaining beneficial H. pylori-mediated factors in extra-gastric tissues; and (3) the feasibility of using antibiotics targeting the microbial DNA damage system, which shares commonalities with mechanisms for human cell replication, as chemopreventives. Additional therapeutic perspectives are also discussed.
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Affiliation(s)
- Alexios-Fotios A Mentis
- Department of Medical Microbiology, Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece
- Department of Microbiology, University Hospital of Larissa, University of Thessaly, Larissa, Greece
| | - Marina Boziki
- Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nikolaos Grigoriadis
- Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
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31
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von Frieling J, Fink C, Hamm J, Klischies K, Forster M, Bosch TCG, Roeder T, Rosenstiel P, Sommer F. Grow With the Challenge - Microbial Effects on Epithelial Proliferation, Carcinogenesis, and Cancer Therapy. Front Microbiol 2018; 9:2020. [PMID: 30294304 PMCID: PMC6159313 DOI: 10.3389/fmicb.2018.02020] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 08/09/2018] [Indexed: 12/11/2022] Open
Abstract
The eukaryotic host is in close contact to myriads of resident and transient microbes, which influence the crucial physiological pathways. Emerging evidence points to their role of host-microbe interactions for controlling tissue homeostasis, cell fate decisions, and regenerative capacity in epithelial barrier organs including the skin, lung, and gut. In humans and mice, it has been shown that the malignant tumors of these organs harbor an altered microbiota. Mechanistic studies have shown that the altered metabolic properties and secreted factors contribute to epithelial carcinogenesis and tumor progression. Exciting recent work points toward a crucial influence of the associated microbial communities on the response to chemotherapy and immune-check point inhibitors during cancer treatment, which suggests that the modulation of the microbiota might be a powerful tool for personalized oncology. In this article, we provide an overview of how the bacterial signals and signatures may influence epithelial homeostasis across taxa from cnidarians to vertebrates and delineate mechanisms, which might be potential targets for therapy of human diseases by either harnessing barrier integrity (infection and inflammation) or restoring uncontrolled proliferation (cancer).
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Affiliation(s)
- Jakob von Frieling
- Zoological Institute, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Christine Fink
- Zoological Institute, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Jacob Hamm
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Kenneth Klischies
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Michael Forster
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Thomas C G Bosch
- Zoological Institute, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Thomas Roeder
- Zoological Institute, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
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32
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Abstract
In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated structural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physiology were newly explored this year and evaluated for their functions during stomach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E-cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. pylori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technologies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new insights into how H. pylori manipulates gastric tissue functions, locally and at a distance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experimental infection after vaccination.
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Affiliation(s)
- Langgeng Agung Waskito
- Faculty of Medicine, Department of Environmental and Preventive Medicine, Oita University, Yufu-City, Oita, Japan.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Nina R Salama
- Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Yoshio Yamaoka
- Faculty of Medicine, Department of Environmental and Preventive Medicine, Oita University, Yufu-City, Oita, Japan.,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas
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33
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Okushin K, Tsutsumi T, Ikeuchi K, Kado A, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Koike K. Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis. World J Gastroenterol 2018; 24:3617-3625. [PMID: 30166857 PMCID: PMC6113725 DOI: 10.3748/wjg.v24.i32.3617] [Citation(s) in RCA: 42] [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: 04/26/2018] [Revised: 05/30/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.
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Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Akira Kado
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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34
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Bravo D, Hoare A, Soto C, Valenzuela MA, Quest AFG. Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World J Gastroenterol 2018; 24:3071-3089. [PMID: 30065554 PMCID: PMC6064966 DOI: 10.3748/wjg.v24.i28.3071] [Citation(s) in RCA: 139] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/17/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
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Affiliation(s)
- Denisse Bravo
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Anilei Hoare
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Cristopher Soto
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Manuel A Valenzuela
- Advanced Center for Chronic Diseases, Institute for Health-Related Research and Innovation, Faculty of Health Sciences, Universidad Central de Chile, Santiago 8380447, Chile
| | - Andrew FG Quest
- Advanced Center for Chronic Diseases, Center for Studies on Exercise, Metabolism and Cancer, Biomedical Science Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380447, Chile
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Zhai Z, Huang X, Yin Y. Beyond immunity: The Imd pathway as a coordinator of host defense, organismal physiology and behavior. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2018; 83:51-59. [PMID: 29146454 DOI: 10.1016/j.dci.2017.11.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 11/10/2017] [Accepted: 11/13/2017] [Indexed: 06/07/2023]
Abstract
The humoral arm of host defense in Drosophila relies on two evolutionarily conserved NFκB signaling cascades, the Toll and the immune deficiency (Imd) pathways. The Imd signaling pathway senses and neutralizes Gram-negative bacteria. Its activity is tightly adjusted, allowing the host to simultaneously prevent infection by pathogenic bacteria and tolerate beneficial gut microbiota. Over-activation of Imd signaling is detrimental at least in part by causing gut dysbiosis that further exacerbates intestinal pathologies. Furthermore, it is increasingly recognized that the Imd pathway or its components also play non-immune roles. In this review, we summarize recent advances in Imd signal transduction, discuss the gut-microbiota interactions mediated by Imd signaling, and finally elaborate on its diverse physiological functions beyond immunity. Understanding the multifaceted physiological outputs of Imd activation will help integrate its immune role into the regulation of whole organismal physiology.
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Affiliation(s)
- Zongzhao Zhai
- Changsha Medical University, 410125 Changsha, China; Animal Nutrition and Human Health Laboratory, School of Life Sciences, Hunan Normal University, 410081 Changsha, Hunan, China.
| | | | - Yulong Yin
- Changsha Medical University, 410125 Changsha, China; Animal Nutrition and Human Health Laboratory, School of Life Sciences, Hunan Normal University, 410081 Changsha, Hunan, China
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36
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Racing to Stay Put: How Resident Microbiota Stimulate Intestinal Epithelial Cell Proliferation. CURRENT PATHOBIOLOGY REPORTS 2018. [DOI: 10.1007/s40139-018-0163-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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