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Astúa A, Estevez MC, Ramírez-Lázaro MJ, Calvet X, Lario S, Lechuga LM. Identification and ultrasensitive quantification of H. pylori infections on gastric and stool human samples with a photonic label-free nanobiosensor. Biosens Bioelectron 2025; 281:117459. [PMID: 40233488 DOI: 10.1016/j.bios.2025.117459] [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: 01/10/2025] [Revised: 03/31/2025] [Accepted: 04/07/2025] [Indexed: 04/17/2025]
Abstract
Helicobacter pylori is a widespread bacterium that infects the stomach, causing gastric disorders associated with high morbidity and mortality worldwide. Current methods for identifying and quantifying this pathogen rely on invasive and non-invasive tests. Although combining these methods allows accurate diagnosis, they have multiple drawbacks, and there is no single reliable gold standard test. New, more sensitive strategies involving molecular techniques, such as digital PCR, have been developed but require complex and expensive instruments. Herein, we implement and validat a nanophotonic bimodal waveguide (BiMW) biosensor for the sensitive and accurate detection of H. pylori in gastric biopsies and stool. This biosensor offers real-time, label-free detection, high sensitivity, and the capability to be integrated into compact devices. By employing monoclonal antibodies targeting specific membrane proteins found in H. pylori, the biosensor enables unique recognition of the bacterium, demonstrating its potential as an alternative diagnostic tool. The BiMW biosensor provides highly accurate H. pylori quantification in under 20 min, with limits of detection (LOD) of 89 ± 35 CFU/mL for antrum gastric biopsies and 82 ± 9 CFU/mL for stool samples. Clinical validation with 40 samples (20 gastric biopsies and 20 stool samples) showed sensitivity and specificity of 90 % for gastric biopsies and 95 % for stool samples, offering diagnostic reliability equivalent to semiquantitative ELISA tests and enabling more efficient and timely detection of H. pylori infections. This test can significantly improve the speed of diagnosis and contribute to the development of more effective strategies for H. pylori eradication.
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Affiliation(s)
- Alejandro Astúa
- Nanobiosensors and Bioanalytical Applications Group (nanoB2A), Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, CIBER-BBN, BIST, Bellaterra, 08193, Barcelona, Spain
| | - M-Carmen Estevez
- Nanobiosensors and Bioanalytical Applications Group (nanoB2A), Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, CIBER-BBN, BIST, Bellaterra, 08193, Barcelona, Spain.
| | - M José Ramírez-Lázaro
- Digestive Diseases Service, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Barcelona, 08208, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Xavier Calvet
- Digestive Diseases Service, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Barcelona, 08208, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Sergio Lario
- Digestive Diseases Service, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Barcelona, 08208, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Laura M Lechuga
- Nanobiosensors and Bioanalytical Applications Group (nanoB2A), Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, CIBER-BBN, BIST, Bellaterra, 08193, Barcelona, Spain
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Jeon JH, Lee J, Baek YJ, Lim KJ, Kim JD, Park JS, Choi MK, Song IS. Restoration of intestinal barrier function by fexuprazan, a potassium-competitive acid blocker, in Caco-2 cells and its higher gastrointestinal distribution in rats. Biomed Pharmacother 2025; 188:118185. [PMID: 40412363 DOI: 10.1016/j.biopha.2025.118185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 05/12/2025] [Accepted: 05/21/2025] [Indexed: 05/27/2025] Open
Abstract
This study aimed to investigate the efficacy of fexuprazan in restoring intestinal barrier function in comparison with other potassium-competitive acid blockers (P-CABs) and esomeprazole. The effect of fexuprazan on trans-epithelial electrical resistance (TEER) value, mRNA and protein expression of tight junction genes, and cell morphology was investigated using a dextran sulfate sodium (DSS)-induced ulcerative colitis Caco-2 cell model. Treatment with fexuprazan, esomeprazole, tegoprazan, and vonoprazan significantly increased TEER values in a 3 % DSS-induced ulcerative colitis Caco-2 cells in a concentration-dependent manner. The TEER value-concentration profile showed sigmoidal shape curves and yielded half maximal effective concentration of 0.983 - 1.17 μg/mL for P-CABs and 3.27 μg/mL for esomeprazole. Among these drugs, fexuprazan showed the highest activity in the restoring intestinal barrier function. Fexuprazan also increased the expression of tight junction genes including zonula occludens-1, claudin 1, occludin, and mucin 1, and also thickened the epithelial cell membrane after treatment with 20 μg/mL fexuprazan. Fexuprazan showed a particularly high distribution in the liver and gastrointestinal tract in rats following oral administration of 2 mg/kg fexuprazan, which appears to be a positive characteristic of fexuprazan's effect on ulcerative colitis and gastric acid-related diseases although in vivo therapeutic efficacy of fexuprazan for ulcerative colitis requires further validation in both animal and human. In conclusion, fexuprazan can potentially restore intestinal barrier function by increasing the expression of tight junction genes and by strengthening the cell membrane integrity in DSS-induced colitis model.
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Affiliation(s)
- Ji-Hyeon Jeon
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jihoon Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; Vessel‑Organ Interaction Research Center (VOICE) and BK21 FOUR Community‑Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Yeon-Ju Baek
- College of Pharmacy, Dankook University, Cheon‑an 31116, Republic of Korea
| | - Kwon-Jo Lim
- Life Science Institute, Daewoong Pharmaceutical, Yongin, Gyeonggido 17028, Republic of Korea
| | - Ji Duck Kim
- Life Science Institute, Daewoong Pharmaceutical, Yongin, Gyeonggido 17028, Republic of Korea
| | - Joon Seok Park
- Life Science Institute, Daewoong Pharmaceutical, Yongin, Gyeonggido 17028, Republic of Korea
| | - Min-Koo Choi
- College of Pharmacy, Dankook University, Cheon‑an 31116, Republic of Korea
| | - Im-Sook Song
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; Vessel‑Organ Interaction Research Center (VOICE) and BK21 FOUR Community‑Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, Republic of Korea.
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Auchtung JM, Hallen-Adams HE, Hutkins R. Microbial interactions and ecology in fermented food ecosystems. Nat Rev Microbiol 2025:10.1038/s41579-025-01191-w. [PMID: 40410356 DOI: 10.1038/s41579-025-01191-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/06/2025] [Indexed: 05/25/2025]
Abstract
Fermented foods and beverages, produced by the intentional growth of microorganisms, have long been among the most widely consumed foods in the human diet. Whether microorganisms are added directly to food substrates, or the growth and activity of autochthonous microorganisms colonizing food substrates is encouraged by selective conditions, the production of organic acids, ethanol and other metabolic end products enhance the safety, shelf-life, sensory and functional properties of foods. Whereas some fermented foods may be produced by communities dominated by only a few taxa of limited phylogenetic diversity, others are produced through the concerted action of diverse microbial communities. In this Review, we describe the ecological interactions shaping microbial community structure and function across various categories of fermented foods by providing specific examples. We also describe how the manufacture, quality and sustainability of even traditional fermented foods can be improved by contemporary technologies. Finally, we briefly discuss current research on the ecological impact of microorganisms found in fermented food on the human gut.
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Affiliation(s)
- Jennifer M Auchtung
- Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska, Lincoln, NE, USA.
| | - Heather E Hallen-Adams
- Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska, Lincoln, NE, USA
| | - Robert Hutkins
- Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska, Lincoln, NE, USA.
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4
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Kuc N, Feldman A, Small I, Cynamon J, Gohari A. Balloon assisted gastrostomy tube placement. Abdom Radiol (NY) 2025:10.1007/s00261-025-04962-4. [PMID: 40304751 DOI: 10.1007/s00261-025-04962-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/10/2025] [Accepted: 04/17/2025] [Indexed: 05/02/2025]
Abstract
PURPOSE To compare the safety and efficacy of balloon-assisted gastrostomy (BAG) placement to the conventional serial dilation technique. METHODS This study is an IRB-approved retrospective review of all percutaneous gastrostomy tubes placed by an interventional radiology department at a single institution between 2012 and 2021. There were 476 patients identified (average age 63, 44% female): 385 in the serial dilation group and 91 in the balloon assisted gastrostomy (BAG) group. Patient demographic, procedure, and radiological data were reviewed in the medical record to determine procedure success, procedure/fluoroscopy time, and tube failures. Gastrostomy tube failure was defined as tube leak, clogging, or dislodgement. Adverse events were classified as per Society of Interventional Radiology guidelines. Statistical analysis was performed using Fisher's exact test, student's t-test, and Mann-Whitney U-test as appropriate. RESULTS Gastrostomy tubes were successfully placed in 97.7% (377/385) of patients undergoing the serial dilation technique and 100% (91/91) of patients undergoing the BAG placement technique. BAG tube placement was associated with a 2.5 min decrease (47%) in average fluoroscopy time (p = 0.0002, CI: 3.76 to 1.20). Total procedure time was reduced by an average of 17.2 min (22%) (p = 0.0006, CI: 26.9 to 7.4). BAG was also associated with an 11% reduction in all cause gastrostomy tube failure (p = 0.0399). There were no statistically significant differences in the adverse event rates or median days to tube failure. Material costs were $178.32 higher in the BAG group. CONCLUSION BAG catheter placement can be performed safely and effectively, and is associated with reduced fluoroscopy time, procedure time, and overall failure rate compared to the serial dilation technique.
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Affiliation(s)
- Norbert Kuc
- Montefiore Medical Center, The Bronx, USA.
- Albert Einstein College of Medicine, The Bronx, USA.
| | - Ariel Feldman
- Albert Einstein College of Medicine, The Bronx, USA
- Columbia University Irving Medical Center, New York, USA
| | - Ilan Small
- St. John's Riverside Hospital, Yonkers, USA
| | - Jacob Cynamon
- Montefiore Medical Center, The Bronx, USA
- Albert Einstein College of Medicine, The Bronx, USA
| | - Arash Gohari
- Montefiore Medical Center, The Bronx, USA
- Albert Einstein College of Medicine, The Bronx, USA
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Akpoghelie PO, Edo GI, Mafe AN, Isoje EF, Igbuku UA, Ali ABM, Yousif E, Owheruo JO, Oberhiri Oberhiri S, Essaghah AEA, Ahmed DS, Umar H, Alamiery AA. Food, Health, and Environmental Impact of Lactic Acid Bacteria: The Superbacteria for Posterity. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10546-x. [PMID: 40289239 DOI: 10.1007/s12602-025-10546-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2025] [Indexed: 04/30/2025]
Abstract
Lactic acid bacteria (LAB) are Gram-positive cocci or rods that do not produce spores or respire. Their primary function is to ferment carbohydrates and produce lactic acid. The two primary forms of LAB that are currently recognized are homofermentative and heterofermentative. This review discusses the evolutionary diversity and the biochemical and biophysical conditions required by LAB for their metabolism. Next, it concentrates on the applications of these bacteria in gut health, cancer prevention, and overall well-being and food systems. There are numerous uses for LAB, including the food and dairy sectors, as probiotics to improve human and animal gut-health, as anti-carcinogenic agents, and in food safety as biopreservatives, pathogen inhibitors, and reducers of anti-nutrients in foods. The group included many genera, including Aerococcus, Carnobacterium, Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Streptococcus, Tetragenococcus, Vagococcus, and Weissella. Numerous species of Lactobacillus and Bifidobacterium genera as well as other microbes have been suggested as probiotic strains, or live microorganisms added to meals to improve health. LAB can colonize the intestine and take part in the host's physiological processes. This review briefly highlights the role of these bacteria in food safety and security as well as aspects of regulation and consumer acceptance. Finally, the recent innovations in LAB fermentations and the limitations and challenges of the applications of LAB in the food industry are discussed. Notwithstanding recent developments, the study of LAB and their functional components is still an emerging topic of study that has not yet realized its full potential.
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Affiliation(s)
- Patrick Othuke Akpoghelie
- Department of Food Science and Technology, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Great Iruoghene Edo
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria.
- Department of Chemistry, College of Sciences, Al-Nahrain University, Baghdad, Iraq.
| | - Alice Njolke Mafe
- Department of Biological Sciences, Faculty of Science, Taraba State University Jalingo, Taraba State, Jalingo, Nigeria
| | - Endurance Fegor Isoje
- Faculty of Science, Department of Science Laboratory Technology (Biochemistry Option), Delta State University of Science and Technology, Ozoro, Nigeria
| | - Ufuoma Augustina Igbuku
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Ali B M Ali
- Department of Air Conditioning Engineering, College of Engineering, Warith Al-Anbiyaa University, Karbala, Iraq
| | - Emad Yousif
- Department of Chemistry, College of Sciences, Al-Nahrain University, Baghdad, Iraq
| | - Joseph Oghenewogaga Owheruo
- Department of Food Science and Technology, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | | | - Arthur Efeoghene Athan Essaghah
- Faculty of Environmental Sciences, Department of Urban and Regional Planning, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Dina S Ahmed
- Department of Chemical Industries, Institute of Technology-Baghdad, Middle Technical University, Baghdad, Iraq
| | - Huzaifa Umar
- Operational Research Centre in Healthcare, Near East University, Nicosia, Cyprus
| | - Ahmed A Alamiery
- AUIQ, Al-Ayen Scientific Research Center, Al-Ayen Iraqi University, P.O. Box: 64004, An Nasiriyah, Thi Qar, Iraq
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Zhou C, Bisseling TM, van der Post RS, Boleij A. The influence of Helicobacter pylori, proton pump inhibitor, and obesity on the gastric microbiome in relation to gastric cancer development. Comput Struct Biotechnol J 2024; 23:186-198. [PMID: 38075398 PMCID: PMC10704269 DOI: 10.1016/j.csbj.2023.11.053] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 11/27/2023] [Accepted: 11/27/2023] [Indexed: 05/11/2025] Open
Abstract
Helicobacter pylori infection is still the main risk factor for the development of gastric cancer (GC). We explore the scientific evidence for the role of the gastric microbiome beyond Helicobacter pylori (H. pylori) in gastric carcinogenesis. The composition of the gastric microbiome in healthy individuals, in presence and absence of H. pylori infection, in proton pump inhibitor (PPI)-users, obese individuals, and GC patients was investigated. Possible mechanisms for microbial involvement, limitations of available research and options for future studies are provided. A common finding amongst studies was increased levels of Streptococcus, Prevotella, Neisseria, and Actinomyces in healthy individuals or those with H. pylori-negative gastritis. In PPI-users the risk for GC increases with the treatment duration, and the gastric microbiome shifts, with the most consistent increase in the genus Streptococcus. Similarly, in obese individuals, Streptococcus was the most abundant genus, with an increased risk for cardia GC. The genera Streptococcus, Lactobacillus and Prevotella were found to be more prominent in GC patients in multiple studies. Potential mechanisms of non-H. pylori microbiota contributing to GC are linked to lipopolysaccharide production, contribution to inflammatory pathways, and the formation of N-nitroso compounds and reactive oxygen species. In conclusion, the knowledge of the gastric microbiome in GC is mainly descriptive and based on sequencing of gastric mucosal samples. For a better mechanistic understanding of microbes in GC development, longitudinal cohorts including precancerous lesions, different regions in the stomach, and subtypes of GC, and gastric organoid models for diffuse and intestinal type GC should be employed.
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Affiliation(s)
- Chengliang Zhou
- Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, P.O. box 9101, 6500 HB Nijmegen, the Netherlands
| | - Tanya M. Bisseling
- Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Gastroenterology and Hepatology, P.O. box 9101, 6500 HB Nijmegen, the Netherlands
| | - Rachel S. van der Post
- Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, P.O. box 9101, 6500 HB Nijmegen, the Netherlands
| | - Annemarie Boleij
- Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, P.O. box 9101, 6500 HB Nijmegen, the Netherlands
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Wang SN, Yun T, Zhu CY, Li P, Ge DF, Li SL, Wang YK. Immune cell changes in Helicobacter pylori infection-induced glandular epithelial cell damage of the gastric mucosa. Ann Med 2024; 56:2425072. [PMID: 39512155 PMCID: PMC11552272 DOI: 10.1080/07853890.2024.2425072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 09/13/2024] [Accepted: 10/25/2024] [Indexed: 11/15/2024] Open
Abstract
OBJECTIVE The purpose of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes. METHODS We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori-infected gastric mucosal specimens. RESULTS Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression. CONCLUSION For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.
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Affiliation(s)
- Su-Nan Wang
- Shenzhen Polytechnic University, Shenzhen, China
| | - Tian Yun
- Department of Pathology, The 989th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Luoyang, Henan, China
| | - Chao-Ya Zhu
- Department of Pathology, Third Affiliated Hospital of Zhengzhou University, Shenzhen, China
| | - Ping Li
- Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Dong-Feng Ge
- Department of Pathology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Shen-Lin Li
- Department of Pathology, The Fourth People’s Hospital of Longgang District, Shenzhen, Shenzhen, China
| | - Yang-Kun Wang
- Department of Pathology, The Fourth People’s Hospital of Longgang District, Shenzhen, Shenzhen, China
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Petkevicius V, Lehr K, Kupcinskas J, Link A. Fusobacterium nucleatum: Unraveling its potential role in gastric carcinogenesis. World J Gastroenterol 2024; 30:3972-3984. [PMID: 39351058 PMCID: PMC11438658 DOI: 10.3748/wjg.v30.i35.3972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/09/2024] [Accepted: 08/27/2024] [Indexed: 09/13/2024] Open
Abstract
Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.
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Affiliation(s)
- Vytenis Petkevicius
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
| | - Konrad Lehr
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
| | - Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas 50161, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
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Sokou R, Moschari E, Palioura AE, Palioura AP, Mpakosi A, Adamakidou T, Vlachou E, Theodoraki M, Iacovidou N, Tsartsalis AN. The Impact of Gestational Diabetes Mellitus (GDM) on the Development and Composition of the Neonatal Gut Microbiota: A Systematic Review. Microorganisms 2024; 12:1564. [PMID: 39203408 PMCID: PMC11356352 DOI: 10.3390/microorganisms12081564] [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: 07/01/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 09/03/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is an important health issue, as it is connected with adverse effects to the mother as well as the fetus. A factor of essence for the pathology of this disorder is the gut microbiota, which seems to have an impact on the development and course of GDM. The role of the gut microbiota on maternal reproductive health and all the changes that happen during pregnancy as well as during the neonatal period is of high interest. The correct establishment and maturation of the gut microbiota is of high importance for the development of basic biological systems. The aim of this study is to provide a systematic review of the literature on the effect of GDM on the gut microbiota of neonates, as well as possible links to morbidity and mortality of neonates born to mothers with GDM. Systematic research took place in databases including PubMed and Scopus until June 2024. Data that involved demographics, methodology, and changes to the microbiota were derived and divided based on patients with exposure to or with GDM. The research conducted on online databases revealed 316 studies, of which only 16 met all the criteria and were included in this review. Research from the studies showed great heterogeneity and varying findings at the level of changes in α and β diversity and enrichment or depletion in phylum, gene, species, and operational taxonomic units in the neonatal gut microbiota of infants born to mothers with GDM. The ways in which the microbiota of neonates and infants are altered due to GDM remain largely unclear and require further investigation. Future studies are needed to explore and clarify these mechanisms.
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Affiliation(s)
- Rozeta Sokou
- Neonatal Intensive Care Unit, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece; (E.M.); (A.E.P.); (A.-P.P.); (M.T.)
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 11528 Athens, Greece;
| | - Eirini Moschari
- Neonatal Intensive Care Unit, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece; (E.M.); (A.E.P.); (A.-P.P.); (M.T.)
| | - Alexia Eleftheria Palioura
- Neonatal Intensive Care Unit, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece; (E.M.); (A.E.P.); (A.-P.P.); (M.T.)
| | - Aikaterini-Pothiti Palioura
- Neonatal Intensive Care Unit, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece; (E.M.); (A.E.P.); (A.-P.P.); (M.T.)
| | - Alexandra Mpakosi
- Department of Microbiology, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece;
| | - Theodoula Adamakidou
- Department of Nursing, School of Health Sciences, University of West Attica, Ag. Spydironos 28, 12243 Athens, Greece; (T.A.); (E.V.)
| | - Eugenia Vlachou
- Department of Nursing, School of Health Sciences, University of West Attica, Ag. Spydironos 28, 12243 Athens, Greece; (T.A.); (E.V.)
| | - Martha Theodoraki
- Neonatal Intensive Care Unit, General Hospital of Nikea “Agios Panteleimon”, 18454 Piraeus, Greece; (E.M.); (A.E.P.); (A.-P.P.); (M.T.)
| | - Nicoletta Iacovidou
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 11528 Athens, Greece;
| | - Athanasios N. Tsartsalis
- Department of Endocrinology Diabetes and Metabolism, Naval Hospital of Athens, Dinokratous 70, 11521 Athens, Greece;
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Smith SI, Schulz C, Ugiagbe R, Ndip R, Dieye Y, Leja M, Onyekwere C, Ndububa D, Ajayi A, Jolaiya TF, Jaka H, Setshedi M, Gunturu R, Otegbayo JA, Lahbabi-Amrani N, Arigbabu AO, Kayamba V, Nashidengo PA. Helicobacter pylori Diagnosis and Treatment in Africa: The First Lagos Consensus Statement of the African Helicobacter and Microbiota Study Group. Dig Dis 2024; 42:240-256. [PMID: 38493766 DOI: 10.1159/000537878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 02/14/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.
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Affiliation(s)
- Stella I Smith
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Rose Ugiagbe
- Department of Medicine, University of Benin Teaching Hospital, Benin, Nigeria
| | - Roland Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Yakhya Dieye
- Pole of Microbiology, Institut Pasteur de Dakar, Dakar, Senegal
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Charles Onyekwere
- Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Nigeria
| | - Dennis Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - Abraham Ajayi
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | | | - Hyasinta Jaka
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Mashiko Setshedi
- Departments of Medicine, Division of Gastroenterology, University of Cape Town, Cape Town, South Africa
| | - Revathi Gunturu
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | | | - Naima Lahbabi-Amrani
- Faculty of Medicine and Pharmacy in Rabat, University Mohammed V, Rabat, Morocco
| | | | - Violet Kayamba
- Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia
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11
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Zhao H, Ma J, Tang Y, Ma X, Li J, Li H, Liu Z. Genome-wide DNA N6-methyladenosine in Aeromonas veronii and Helicobacter pylori. BMC Genomics 2024; 25:161. [PMID: 38331763 PMCID: PMC10854192 DOI: 10.1186/s12864-024-10074-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] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 02/01/2024] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND DNA N6-methyladenosine (6mA), as an important epigenetic modification, widely exists in bacterial genomes and participates in the regulation of toxicity, antibiotic resistance, and antioxidant. With the continuous development of sequencing technology, more 6mA sites have been identified in bacterial genomes, but few studies have focused on the distribution characteristics of 6mA at the whole-genome level and its association with gene expression and function. RESULTS This study conducted an in-depth analysis of the 6mA in the genomes of two pathogenic bacteria, Aeromonas veronii and Helicobacter pylori. The results showed that the 6mA was widely distributed in both strains. In A. veronii, 6mA sites were enriched at 3' end of protein-coding genes, exhibiting a certain inhibitory effect on gene expression. Genes with low 6mA density were associated with cell motility. While in H. pylori, 6mA sites were enriched at 5' end of protein-coding genes, potentially enhancing gene expression. Genes with low 6mA density were closely related to defense mechanism. CONCLUSIONS This study elucidated the distribution characteristics of 6mA in A. veronii and H. pylori, highlighting the effects of 6mA on gene expression and function. These findings provide valuable insights into the epigenetic regulation and functional characteristics of A. veronii and H. pylori.
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Affiliation(s)
- Honghao Zhao
- School of Life and Health Sciences, Hainan University, Haikou, China
| | - Jiayue Ma
- School of Life and Health Sciences, Hainan University, Haikou, China
| | - Yanqiong Tang
- School of Life and Health Sciences, Hainan University, Haikou, China
| | - Xiang Ma
- School of Life and Health Sciences, Hainan University, Haikou, China
| | - Juanjuan Li
- School of Life and Health Sciences, Hainan University, Haikou, China
| | - Hong Li
- School of Life and Health Sciences, Hainan University, Haikou, China.
| | - Zhu Liu
- School of Life and Health Sciences, Hainan University, Haikou, China.
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12
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Martin A, Jauvain M, Bergsten E, Demontant V, Lehours P, Barau C, Levy M, Rodriguez C, Sobhani I, Amiot A. Gastric microbiota in patients with gastric MALT lymphoma according to Helicobacter pylori infection. Clin Res Hepatol Gastroenterol 2024; 48:102247. [PMID: 37981222 DOI: 10.1016/j.clinre.2023.102247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/12/2023] [Accepted: 11/15/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Gastric Mucosa Associated Lymphoid Tissue lymphoma (GML) development is triggered by Helicobacter pylori (H. pylori) infection. Little is known about the impact of H. pylori infection on gastric microbiota. METHODS The gastric microbiota was retrospectively investigated using 16S rRNA gene sequencing in 32 patients with untreated GML (10 H. pylori-positive and 22 H. pylori-negative), 23 with remitted and 18 refractory GML and 35 controls. Differences in microbial diversity, bacterial composition and taxonomic repartition were assessed. RESULTS There was no change in diversity and bacterial composition between GML and control patients taking into account H. pylori status. Differential taxa analysis identified specific changes associated with H. pylori-negative GML: the abundances of Actinobacillus, Lactobacillus and Chryseobacterium were increased while the abundances of Veillonella, Atopobium, Leptotrichia, Catonella, Filifactor and Escherichia_Shigella were increased in control patients. In patients with remitted GML, the genera Haemophilus and Moraxella were significantly more abundant than in refractory patients, while Atopobium and Actinomyces were significantly more abundant in refractory patients. CONCLUSION Detailed analysis of the gastric microbiota revealed significant changes in the bacterial composition of the gastric mucosa in patients with GML that may have a role in gastric lymphomagenesis but not any new pathobionts.
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Affiliation(s)
- Antoine Martin
- Department of Gastroenterology, Henri-Mondor University Hospital, Universite Paris Est Creteil, AP-HP, EA7375, 51, Avenue du Marechal de Lattre de Tassigny CRETEIL, Creteil F-94010, France
| | - Marine Jauvain
- UMR1312 Bordeaux Institute of Cancer, BRIC, Université de Bordeaux, Bordeaux 33076, France; French National Reference Center for Campylobacters and Helicobacters, Bordeaux Hospital University Center, Bordeaux, France
| | - Emma Bergsten
- Department of Gastroenterology, Henri-Mondor University Hospital, Universite Paris Est Creteil, AP-HP, EA7375, 51, Avenue du Marechal de Lattre de Tassigny CRETEIL, Creteil F-94010, France
| | - Vanessa Demontant
- Genomics Platform and Virology Unit, Henri-Mondor University Hospital, AP-HP, Institut Mondor de Recherche Biomédicale, Universite Paris Est Creteil, INSERM U955, Créteil F-94010 France
| | - Philippe Lehours
- UMR1312 Bordeaux Institute of Cancer, BRIC, Université de Bordeaux, Bordeaux 33076, France; French National Reference Center for Campylobacters and Helicobacters, Bordeaux Hospital University Center, Bordeaux, France
| | - Caroline Barau
- Plateforme de Ressources Biologique, Henri-Mondor University Hospital, AP-HP, University Paris Est Creteil, F-94010, France
| | - Michael Levy
- Department of Gastroenterology, Henri-Mondor University Hospital, Universite Paris Est Creteil, AP-HP, EA7375, 51, Avenue du Marechal de Lattre de Tassigny CRETEIL, Creteil F-94010, France
| | - Christophe Rodriguez
- Genomics Platform and Virology Unit, Henri-Mondor University Hospital, AP-HP, Institut Mondor de Recherche Biomédicale, Universite Paris Est Creteil, INSERM U955, Créteil F-94010 France
| | - Iradj Sobhani
- Department of Gastroenterology, Henri-Mondor University Hospital, Universite Paris Est Creteil, AP-HP, EA7375, 51, Avenue du Marechal de Lattre de Tassigny CRETEIL, Creteil F-94010, France
| | - Aurelien Amiot
- Department of Gastroenterology, Henri-Mondor University Hospital, Universite Paris Est Creteil, AP-HP, EA7375, 51, Avenue du Marechal de Lattre de Tassigny CRETEIL, Creteil F-94010, France.
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13
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Xu B, Kong J, Lin Y, Tang Z, Liu J, Chen Z, Zeng W, Bai Y, Fan H. Anti- Helicobacter pylori activity and gastroprotective effects of human stomach-derived Lactobacillus paragasseri strain LPG-9. Food Funct 2023; 14:10882-10895. [PMID: 37987614 DOI: 10.1039/d3fo03562j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
The eradication of Helicobacter pylori is an urgent global issue. However, the traditional regimens have several limitations. Thus, we propose the idea of treating bacterial gastric disease with the objective of eliminating gastric pathogenic bacteria and enhancing gastroprotective effects using gastric probiotics. In this study, a total of 12 Lactobacillus strains were isolated from the gastric mucosa of healthy donors. After evaluation using a weight scoring system, Lactobacillus paragasseri strain LPG-9 was identified as the most promising probiotic for gastric disease, with the highest acid-resistance and the best adhesion characteristics. Gastric colonisation, H. pylori inhibition, anti-inflammatory, and gastric homeostasis effects of LPG-9 were confirmed in C57BL/6 mice. Finally, a safety evaluation and whole-genome sequencing were performed. Based on the results of this study, LPG-9 originates from the gastric microbiota and is a promising probiotic for gastric disease, particularly H. pylori-induced gastritis, providing a solution to this global issue.
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Affiliation(s)
- Binyan Xu
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Jingjing Kong
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
| | - Yangfan Lin
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Ziyu Tang
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
| | - Jiaxin Liu
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
| | - Zhenhui Chen
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
| | - Weiseng Zeng
- Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Yang Bai
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Hongying Fan
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Southern Medical University, Guangzhou, China.
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14
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White Z, Cabrera I, Kapustka I, Sano T. Microbiota as key factors in inflammatory bowel disease. Front Microbiol 2023; 14:1155388. [PMID: 37901813 PMCID: PMC10611514 DOI: 10.3389/fmicb.2023.1155388] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 09/07/2023] [Indexed: 10/31/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) is characterized by prolonged inflammation of the gastrointestinal tract, which is thought to occur due to dysregulation of the immune system allowing the host's cells to attack the GI tract and cause chronic inflammation. IBD can be caused by numerous factors such as genetics, gut microbiota, and environmental influences. In recent years, emphasis on commensal bacteria as a critical player in IBD has been at the forefront of new research. Each individual harbors a unique bacterial community that is influenced by diet, environment, and sanitary conditions. Importantly, it has been shown that there is a complex relationship among the microbiome, activation of the immune system, and autoimmune disorders. Studies have shown that not only does the microbiome possess pathogenic roles in the progression of IBD, but it can also play a protective role in mediating tissue damage. Therefore, to improve current IBD treatments, understanding not only the role of harmful bacteria but also the beneficial bacteria could lead to attractive new drug targets. Due to the considerable diversity of the microbiome, it has been challenging to characterize how particular microorganisms interact with the host and other microbiota. Fortunately, with the emergence of next-generation sequencing and the increased prevalence of germ-free animal models there has been significant advancement in microbiome studies. By utilizing human IBD studies and IBD mouse models focused on intraepithelial lymphocytes and innate lymphoid cells, this review will explore the multifaceted roles the microbiota plays in influencing the immune system in IBD.
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Affiliation(s)
| | | | | | - Teruyuki Sano
- Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
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15
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Abo-Amer YEE, Mohamed AA, Elhoseeny MM, Rezk SM, Abdel-Salam S, Alrohaimi AH, Abdelgeliel AS, Alzahrani SS, Jafri I, Alqahtani LS, Fayad E, Fakhry M, Soliman MY. Association Between Vitamin D Receptor Polymorphism and the Response to Helicobacter Pylori Treatment. Infect Drug Resist 2023; 16:4463-4469. [PMID: 37449247 PMCID: PMC10337687 DOI: 10.2147/idr.s414186] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/10/2023] [Indexed: 07/18/2023] Open
Abstract
Background & Aims This research aimed to determine how variations in the vitamin D receptor gene affected the response of H. pylori infections to eradication therapy. Patients and Methods On 105 adult H. Pylori-positive patients, a prospective cohort study was carried out. PCR was used to genotype all patients' VDR gene polymorphisms. The patients in the study received standard triple eradication medication (clarithromycin 500 mg, amoxicillin 1000 mg, and omeprazole 20 mg) twice daily for 14 days. A stool test for H. pylori Ag was conducted 4 weeks following the end of treatment. Results In our study, the usual triple therapy's H. pylori eradication rate was 75.2%. The successful eradication of H. pylori and VDR rs 2228570 gene polymorphisms was more prevalent in CT gene polymorphism (64.6%) compared to non-responders (19.2%), while treatment failure was more prevalent in CC gene polymorphism (73.1% in non-responders compared to responders 24.1%), which is statistically significant. In regards to the eradication of H. pylori and VDR rs7975232 gene polymorphisms, the success of eradication was more prevalent in AC gene polymorphism (54.4%) vs non-responders (30.4%), while all patients (14) with gene AA (17.7%) are responders to standard treatment, while the failure of treatment was more prevalent in CC gene polymorphism (69.2% in non-responder vs 27.8% in responders) which is statistically significant. Our findings demonstrated a strong correlation between patients' responses to H. pylori treatment and polymorphisms in the VDR gene (ApaI and TaqI) (P 0.05). Conclusion As far as we are aware, this is the first study to identify a potential link between the FokI and Apal VDR polymorphism and treatment response in H pylori-positive patients. To evaluate the findings, more research with larger number of patients and different population is required.
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Affiliation(s)
| | - Amal Ahmed Mohamed
- National Hepatology & Tropical Medicine Research Institute, Department of Biochemistry, Cairo, Egypt
| | | | - Samar M Rezk
- Department of Clinical Nutrition, Mahalla Hepatology Teaching Hospital, El-Mahalla El-Kubra, Elgharbia, Egypt
| | - Sherief Abdel-Salam
- Department of Tropical Medicine, Hepatology & Gastroenterology Unit, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Abdulmohsen H Alrohaimi
- Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia
| | - Asmaa Sayed Abdelgeliel
- Department of Botany & Microbiology, Faculty of Science, South Valley University, Qena, 83523, Egypt
| | - Seham Saeed Alzahrani
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Ibrahim Jafri
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Leena S Alqahtani
- Department of Biochemistry, College of Science, University of Jeddah, Jeddah, 23445, Saudi Arabia
| | - Eman Fayad
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed Fakhry
- Department of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Asyut, Egypt
| | - Moataz Yousry Soliman
- Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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16
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Liu S, Deng Z, Zhu J, Ma Z, Tuo B, Li T, Liu X. Gastric immune homeostasis imbalance: An important factor in the development of gastric mucosal diseases. Biomed Pharmacother 2023; 161:114338. [PMID: 36905807 DOI: 10.1016/j.biopha.2023.114338] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/18/2023] [Accepted: 01/27/2023] [Indexed: 03/11/2023] Open
Abstract
The gastric mucosal immune system is a unique immune organ independent of systemic immunity that not only maintains nutrient absorption but also plays a role in resisting the external environment. Gastric mucosal immune disorder leads to a series of gastric mucosal diseases, including autoimmune gastritis (AIG)-related diseases, Helicobacter pylori (H. pylori)-induced diseases, and various types of gastric cancer (GC). Therefore, understanding the role of gastric mucosal immune homeostasis in gastric mucosal protection and the relationship between mucosal immunity and gastric mucosal diseases is very important. This review focuses on the protective effect of gastric mucosal immune homeostasis on the gastric mucosa, as well as multiple gastric mucosal diseases caused by gastric immune disorders. We hope to offer new prospects for the prevention and treatment of gastric mucosal diseases.
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Affiliation(s)
- Shuhui Liu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Zilin Deng
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Jiaxing Zhu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Zhiyuan Ma
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Taolang Li
- Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Xuemei Liu
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.
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17
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Malfertheiner P, Camargo MC, El-Omar E, Liou JM, Peek R, Schulz C, Smith SI, Suerbaum S. Helicobacter pylori infection. Nat Rev Dis Primers 2023; 9:19. [PMID: 37081005 PMCID: PMC11558793 DOI: 10.1038/s41572-023-00431-8] [Citation(s) in RCA: 338] [Impact Index Per Article: 169.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/17/2023] [Indexed: 04/22/2023]
Abstract
Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
- Medical Department Klinik of Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke Universität, Magdeburg, Germany.
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Emad El-Omar
- Microbiome Research Centre, St George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Richard Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Stella I Smith
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria
| | - Sebastian Suerbaum
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany
- National Reference Center for Helicobacter pylori, Munich, Germany
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18
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Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev 2023; 123:31-72. [PMID: 36317983 PMCID: PMC9837825 DOI: 10.1021/acs.chemrev.2c00431] [Citation(s) in RCA: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Indexed: 01/12/2023]
Abstract
The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.
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Affiliation(s)
- Nikhil Aggarwal
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Shohei Kitano
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Ginette Ru Ying Puah
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - Sandra Kittelmann
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - In Young Hwang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Singapore
Institute of Technology, Singapore 138683, Singapore
| | - Matthew Wook Chang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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19
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Sun Y, Wen M, Liu Y, Wang Y, Jing P, Gu Z, Jiang T, Wang W. The human microbiome: A promising target for lung cancer treatment. Front Immunol 2023; 14:1091165. [PMID: 36817461 PMCID: PMC9936316 DOI: 10.3389/fimmu.2023.1091165] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 01/16/2023] [Indexed: 01/31/2023] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.
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Affiliation(s)
- Ying Sun
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Miaomiao Wen
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Yue Liu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Yu Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Pengyu Jing
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Zhongping Gu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Tao Jiang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Wenchen Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, China
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20
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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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21
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Somiah T, Gebremariam HG, Zuo F, Smirnova K, Jonsson AB. Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines. Sci Rep 2022; 12:20064. [PMID: 36414643 PMCID: PMC9681763 DOI: 10.1038/s41598-022-24311-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/14/2022] [Indexed: 11/24/2022] Open
Abstract
Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors that facilitate adhesion of the bacterium, which is a crucial step in colonization. Lactate utilization has been reported to play a key role in the pathogenicity of different bacterial species. However, this is poorly understood in H. pylori. In this study, we investigated the effect of lactate on H. pylori adhesin gene expression and the regulation of host inflammatory cytokines. We show that the bacterial adhesins SabA and LabA were downregulated at the transcriptional level during incubation of H. pylori with lactate. Downregulation of sabA required the involvement of the two-component system ArsRS, while labA was regulated via the CheA/CheY system, indicating differences in the regulation of these genes in response to lactate. The levels of the proinflammatory cytokines TNF and IL-6 in H. pylori-stimulated macrophages were reduced when lactate was present. Interestingly, glucose did not prevent the secretion of these cytokines. Taken together, our data suggest that lactate affects H. pylori adhesin gene expression and the host response upon infection.
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Affiliation(s)
- Tanvi Somiah
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Hanna G. Gebremariam
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Fanglei Zuo
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Ksenija Smirnova
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Ann-Beth Jonsson
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
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22
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Bodmer M, Itano A, McInnes I. Harnessing the small intestinal axis to resolve systemic inflammation. Front Immunol 2022; 13:1060607. [PMID: 36458009 PMCID: PMC9706197 DOI: 10.3389/fimmu.2022.1060607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 11/01/2022] [Indexed: 08/10/2023] Open
Abstract
This Perspective presents the potential of the Small Intestinal Axis, a sub-division of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining systemic homeostasis without compromising immunity to pathogens. This is achieved through anatomical structures and signaling pathways that link the tolerogenic potential of the proximal small intestine to systemic immunity. Non-live preparations of microbes isolated from human small intestinal mucosa, and the extracellular vesicles (EVs) which they shed, can resolve systemic inflammation without systemic exposure after oral delivery. The mechanism involves primary interactions with pattern recognition receptors followed by trafficking of immune cells through mesenteric lymph nodes. This generates in the periphery a population of circulating CD4+ T cells which have regulatory function but an atypical FoxP3- phenotype. There is no modification of the resident gut microbiome. Discoveries using this novel approach of targeting mucosal microbial elements to the tolerogenic proximal regions of the small intestine are revealing some of the mysteries of the relationship between the gut and immune system.
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Affiliation(s)
- Mark Bodmer
- Research and Development, Evelo Biosciences, Cambridge, MA, United States
| | - Andrea Itano
- Research and Development, Evelo Biosciences, Cambridge, MA, United States
| | - Iain McInnes
- College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
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23
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Host Cell Antimicrobial Responses against Helicobacter pylori Infection: From Biological Aspects to Therapeutic Strategies. Int J Mol Sci 2022; 23:ijms231810941. [PMID: 36142852 PMCID: PMC9504325 DOI: 10.3390/ijms231810941] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/13/2022] [Accepted: 09/16/2022] [Indexed: 02/07/2023] Open
Abstract
The colonization of Helicobacter pylori (H. pylori) in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including amoxicillin, clarithromycin, furazolidone, levofloxacin, metronidazole, and tetracycline, are commonly used and considered the major treatment regimens for H. pylori eradication, which is, however, becoming less effective by the increasing prevalence of H pylori resistance. Thus, it is urgent to understand the molecular mechanisms of H. pylori pathogenesis and develop alternative therapeutic strategies. In this review, we focus on the virulence factors for H. pylori colonization and survival within host gastric mucosa and the host antimicrobial responses against H. pylori infection. Moreover, we describe the current treatments for H. pylori eradication and provide some insights into new therapeutic strategies for H. pylori infection.
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24
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Aziz S, Rasheed F, Akhter TS, Zahra R, König S. Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer. Molecules 2022; 27:molecules27175410. [PMID: 36080177 PMCID: PMC9458002 DOI: 10.3390/molecules27175410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/12/2022] [Accepted: 08/20/2022] [Indexed: 11/24/2022] Open
Abstract
(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.
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Affiliation(s)
- Shahid Aziz
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad 44000, Pakistan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
- IZKF Core Unit Proteomics, University of Münster, 48149 Münster, Germany
- Correspondence: or
| | - Faisal Rasheed
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad 44000, Pakistan
| | - Tayyab Saeed Akhter
- The Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi 46300, Pakistan
| | - Rabaab Zahra
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Simone König
- IZKF Core Unit Proteomics, University of Münster, 48149 Münster, Germany
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25
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Fakharian F, Asgari B, Nabavi-Rad A, Sadeghi A, Soleimani N, Yadegar A, Zali MR. The interplay between Helicobacter pylori and the gut microbiota: An emerging driver influencing the immune system homeostasis and gastric carcinogenesis. Front Cell Infect Microbiol 2022; 12:953718. [PMID: 36046747 PMCID: PMC9423097 DOI: 10.3389/fcimb.2022.953718] [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] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023] Open
Abstract
The human gut microbiota are critical for preserving the health status because they are required for digestion and nutrient acquisition, the development of the immune system, and energy metabolism. The gut microbial composition is greatly influenced by the colonization of the recalcitrant pathogen Helicobacter pylori (H. pylori) and the conventional antibiotic regimens that follow. H. pylori is considered to be the main microorganism in gastric carcinogenesis, and it appears to be required for the early stages of the process. However, a non-H. pylori microbiota profile is also suggested, primarily in the later stages of tumorigenesis. On the other hand, specific groups of gut microbes may produce beneficial byproducts such as short-chain fatty acids (acetate, butyrate, and propionate) that can modulate inflammation and tumorigenesis pathways. In this review, we aim to present how H. pylori influences the population of the gut microbiota to modify the host immunity and trigger the development of gastric carcinogenesis. We will also highlight the effect of the gut microbiota on immunotherapeutic approaches such as immune checkpoint blockade in cancer treatment to present a perspective for further development of innovative therapeutic paradigms to prevent the progression of H. pylori-induced stomach cancer.
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Affiliation(s)
- Farzaneh Fakharian
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnoush Asgari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Soleimani
- Department of Microbiology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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26
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Taillieu E, Chiers K, Amorim I, Gärtner F, Maes D, Van Steenkiste C, Haesebrouck F. Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health. Vet Res 2022; 53:42. [PMID: 35692057 PMCID: PMC9190127 DOI: 10.1186/s13567-022-01059-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/10/2022] [Indexed: 12/14/2022] Open
Abstract
This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric "non-Helicobacter (H.) pylori Helicobacter species" (NHPH) are less well-known than the human adapted H. pylori. Helicobacter suis has been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of the pars oesophagea of the porcine stomach. The stomach of dogs and cats can be colonized by several Helicobacter species but their pathogenic significance for these animals is probably low. Helicobacter suis as well as several canine and feline gastric Helicobacter species may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, for H. suis, also consumption of contaminated pork. It has been described that standard H. pylori eradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcine H. suis strains are intrinsically less susceptible to aminopenicillins than non-human primate H. suis strains and other gastric Helicobacter species. Virulence factors of H. suis and the canine and feline gastric Helicobacter species include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors in H. pylori. It can be concluded that besides H. pylori, gastric Helicobacter species associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.
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Affiliation(s)
- Emily Taillieu
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
| | - Koen Chiers
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Irina Amorim
- Instituto de Investigação E Inovação Em Saúde (i3S), Universidade Do Porto, Porto, Portugal.,Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal.,School of Medicine and Biomedical Sciences, Porto University, Porto, Portugal
| | - Fátima Gärtner
- Instituto de Investigação E Inovação Em Saúde (i3S), Universidade Do Porto, Porto, Portugal.,Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal
| | - Dominiek Maes
- Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Christophe Van Steenkiste
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp University, Edegem, Belgium.,Department of Gastroenterology and Hepatology, General Hospital Maria Middelares, Ghent, Belgium
| | - Freddy Haesebrouck
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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27
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Son M, Park IS, Kim S, Ma HW, Kim JH, Kim TI, Kim WH, Han J, Kim SW, Cheon JH. Novel Potassium-Competitive Acid Blocker, Tegoprazan, Protects Against Colitis by Improving Gut Barrier Function. Front Immunol 2022; 13:870817. [PMID: 35693794 PMCID: PMC9174989 DOI: 10.3389/fimmu.2022.870817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 04/27/2022] [Indexed: 11/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder characterized by prolonged inflammation of the gastrointestinal tract. IBD can result from gut barrier dysfunction, altered gut microbiota, and abnormal intestinal immunity induced by environmental factors in genetically susceptible individuals. Proton pump inhibitors (PPIs) such as rabeprazole are frequently employed for gastric acid inhibition. However, long-term PPI administration can alter the intestinal microbiome composition, possibly worsening IBD severity. The present study revealed that tegoprazan, a potassium-competitive acid blocker, significantly improved colitis in mice and enhanced the intestinal epithelial barrier function. Tegoprazan alleviated gut microbiota dysbiosis and enhanced the growth of Bacteroides vulgatus. In turn, B. vulgatus alleviated intestinal inflammation by inhibiting epithelial adhesion of pathogenic bacteria. Unlike rabeprazole, tegoprazan did not induce gut dysbiosis. Our findings provide novel insights into the potential role of tegoprazan as an intestinal protectant for IBD and as a therapeutic agent for gastric acid-related diseases.
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Affiliation(s)
- Mijeong Son
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - I Seul Park
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Soochan Kim
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyun Woo Ma
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji Hyung Kim
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Jaeyong Han
- Department of Internal Medicine, Cha Ilsan Medical Center, CHA University, Goyang, South Korea
| | - Seung Won Kim
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea
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28
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Sánchez-Alonzo K, Arellano-Arriagada L, Bernasconi H, Parra-Sepúlveda C, Campos VL, Silva-Mieres F, Sáez-Carrillo K, Smith CT, García-Cancino A. An Anaerobic Environment Drives the Harboring of Helicobacter pylori within Candida Yeast Cells. BIOLOGY 2022; 11:biology11050738. [PMID: 35625466 PMCID: PMC9139145 DOI: 10.3390/biology11050738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/07/2022] [Indexed: 11/30/2022]
Abstract
Simple Summary Helicobacter pylori is a pathogen that is associated with a number of gastric pathologies and has adapted to the gastric environment. Outside this organ, stress factors such as oxygen concentration affect the viability of this bacterium. This study aimed to determine if changes in oxygen concentration promoted the entry of H. pylori into the interior of yeast cells of the Candida genus. Co-cultures of H. pylori and Candida strains in Brucella broth plus 5% fetal bovine serum were incubated under microaerobic, anaerobic, or aerobic conditions. Bacteria-like bodies (BLBs) were detected within yeast cells (Y-BLBs) by optical microscopy, identified by molecular techniques, and their viability evaluated by SYTO-9 fluorescence. Co-cultures incubated under the three conditions showed the presence of Y-BLBs, but the highest Y-BLB percentage was present in H. pylori J99 and C. glabrata co-cultures incubated under anaerobiosis. Molecular techniques were used to identify BLBs as H. pylori and SYTO-9 fluorescence confirmed that this bacterium remained viable within yeast cells. In conclusion, although without apparent stress conditions H. pylori harbors within Candida yeast cells, its harboring increases significantly under anaerobic conditions. This endosymbiotic relationship also depends mostly on the H. pylori strain used in the co-culture. Abstract Helicobacter pylori protects itself from stressful environments by forming biofilms, changing its morphology, or invading eukaryotic cells, including yeast cells. There is little knowledge about the environmental factors that influence the endosymbiotic relationship between bacterium and yeasts. Here, we studied if oxygen availability stimulated the growth of H. pylori within Candida and if this was a bacterial- or yeast strain-dependent relationship. Four H. pylori strains and four Candida strains were co-cultured in Brucella broth plus 5% fetal bovine serum, and incubated under microaerobic, anaerobic, or aerobic conditions. Bacteria-like bodies (BLBs) within yeast cells (Y-BLBs) were detected by microscopy. H. pylori was identified by FISH and by PCR amplification of the 16S rRNA gene of H. pylori from total DNA extracted from Y-BLBs from H. pylori and Candida co-cultures. BLBs viability was confirmed by SYTO-9 fluorescence. Higher Y-BLB percentages were obtained under anaerobic conditions and using H. pylori J99 and C. glabrata combinations. Thus, the H. pylori–Candida endosymbiotic relationship is strain dependent. The FISH and PCR results identified BLBs as intracellular H. pylori. Conclusion: Stressful conditions such as an anaerobic environment significantly increased H. pylori growth within yeast cells, where it remained viable, and the bacterium–yeast endosymbiotic relationship was bacterial strain dependent with a preference for C. glabrata.
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Affiliation(s)
- Kimberly Sánchez-Alonzo
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
| | - Luciano Arellano-Arriagada
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
| | | | - Cristian Parra-Sepúlveda
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
| | - Víctor L. Campos
- Laboratory of Environmental Microbiology, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile;
| | - Fabiola Silva-Mieres
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
| | - Katia Sáez-Carrillo
- Department of Statistics, Faculty of Physical and Mathematical Sciences, Universidad de Concepcion, Concepcion 4070386, Chile;
| | - Carlos T. Smith
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
| | - Apolinaria García-Cancino
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepcion 4070386, Chile; (K.S.-A.); (L.A.-A.); (C.P.-S.); (F.S.-M.); (C.T.S.)
- Correspondence: ; Tel.: +56-41-2204144; Fax: +56-41-2245975
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Wang H, Li J, Wu G, Zhang F, Yin J, He Y. The effect of intrinsic factors and mechanisms in shaping human gut microbiota. MEDICINE IN MICROECOLOGY 2022. [DOI: 10.1016/j.medmic.2022.100054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Park JY, Seo H, Kang CS, Shin TS, Kim JW, Park JM, Kim JG, Kim YK. Dysbiotic change in gastric microbiome and its functional implication in gastric carcinogenesis. Sci Rep 2022; 12:4285. [PMID: 35277583 PMCID: PMC8917121 DOI: 10.1038/s41598-022-08288-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 02/25/2022] [Indexed: 12/17/2022] Open
Abstract
Although there is a growing interest in the role of gastric microbiome on the development of gastric cancer, the exact mechanism is largely unknown. We aimed to investigate the changes of gastric microbiome during gastric carcinogenesis, and to predict the functional potentials of the microbiome involved in the cancer development. The gastric microbiome was analyzed using gastric juice samples from 88 prospectively enrolled patients, who were classified into gastritis, gastric adenoma, or early/advanced gastric cancer group. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using next-generation sequencing method. Metagenomic biomarkers were selected using logistic regression models, based on relative abundances at genus level. We used Tax4Fun to predict possible functional pathways of gastric microbiome involved in the carcinogenesis. The microbial diversity continuously decreased in its sequential process of gastric carcinogenesis, from gastritis to gastric cancer. The microbial composition was significantly different among the four groups of each disease status, as well as between the cancer group and non-cancer group. Gastritis group was differently enriched with genera Akkermansia and Lachnospiraceae NK4A136 Group, whereas the cancer group was enriched with Lactobacillus and Veillonella. Predictive analysis of the functional capacity of the microbiome suggested enrichment or depletion of several functional pathways related to carcinogenesis in the cancer group. There are significant changes in the diversity and composition of gastric microbiome during the gastric carcinogenesis process. Gastric cancer was characterized with microbial dysbiosis, along with functional changes potentially favoring carcinogenesis.
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Affiliation(s)
- Jae Yong Park
- Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea
| | - Hochan Seo
- MD Healthcare R&D Institute, World Cup Buk-ro 56-gil, Mapo-gu, Seoul, Republic of Korea
| | - Chil-Sung Kang
- MD Healthcare R&D Institute, World Cup Buk-ro 56-gil, Mapo-gu, Seoul, Republic of Korea
| | - Tae-Seop Shin
- MD Healthcare R&D Institute, World Cup Buk-ro 56-gil, Mapo-gu, Seoul, Republic of Korea
| | - Jong Won Kim
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Joong-Min Park
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea.
| | - Yoon-Keun Kim
- MD Healthcare R&D Institute, World Cup Buk-ro 56-gil, Mapo-gu, Seoul, Republic of Korea.
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Vilchez-Vargas R, Salm F, Znalesniak EB, Haupenthal K, Schanze D, Zenker M, Link A, Hoffmann W. Profiling of the Bacterial Microbiota along the Murine Alimentary Tract. Int J Mol Sci 2022; 23:1783. [PMID: 35163705 PMCID: PMC8836272 DOI: 10.3390/ijms23031783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 12/13/2022] Open
Abstract
Here, the spatial distribution of the bacterial flora along the murine alimentary tract was evaluated using high throughput sequencing in wild-type and Tff3-deficient (Tff3KO) animals. Loss of Tff3 was linked to increased dextran sodium sulfate-induced colitis. This systematic study shows the results of 13 different regions from the esophagus to the rectum. The number of bacterial species (richness) increased from the esophagus to the rectum, from 50 to 200, respectively. Additionally, the bacterial community structure changed continuously; the highest changes were between the upper/middle and lower gastrointestinal compartments when comparing adjacent regions. Lactobacillus was the major colonizer in the upper/middle gastrointestinal tract, especially in the esophagus and stomach. From the caecum, a drastic diminution of Lactobacillus occurred, while members of Lachnospiraceae significantly increased. A significant change occurred in the bacterial community between the ascending and the transverse colon with Bacteroidetes being the major colonizers with relative constant abundance until the rectum. Interestingly, wild-type and Tff3KO animals did not show significant differences in their bacterial communities, suggesting that Tff3 is not involved in alterations of intraluminal or adhesive microbiota but is obviously important for mucosal protection, e.g., of the sensitive stem cells in the colonic crypts probably by a mucus plume.
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Affiliation(s)
- Ramiro Vilchez-Vargas
- Department of Gastroenterology, Hepatology, and Infectiology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany;
| | - Franz Salm
- Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (F.S.); (E.B.Z.); (K.H.)
| | - Eva B. Znalesniak
- Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (F.S.); (E.B.Z.); (K.H.)
| | - Katharina Haupenthal
- Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (F.S.); (E.B.Z.); (K.H.)
| | - Denny Schanze
- Institute of Human Genetics, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (D.S.); (M.Z.)
| | - Martin Zenker
- Institute of Human Genetics, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (D.S.); (M.Z.)
| | - Alexander Link
- Department of Gastroenterology, Hepatology, and Infectiology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany;
| | - Werner Hoffmann
- Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany; (F.S.); (E.B.Z.); (K.H.)
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Kaźmierczak-Siedlecka K, Daca A, Roviello G, Catalano M, Połom K. Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis-what is currently known? Gastric Cancer 2022; 25:1-10. [PMID: 34741681 PMCID: PMC8732854 DOI: 10.1007/s10120-021-01260-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 10/20/2021] [Indexed: 02/07/2023]
Abstract
Currently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.
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Affiliation(s)
| | - Agnieszka Daca
- Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdańsk, Poland
| | - Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - Martina Catalano
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - Karol Połom
- Department of Surgical Oncology, Medical University of Gdansk, ul. Smoluchowskiego 17, 80-214, Gdańsk, Poland
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Avalueva EB, Serkova MY, Sitkin SI. <i>Helicobacter pylori</i>. The survival strategy of a commensal symbiont in the <i>Homo sapiens</i> population. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:102-108. [DOI: 10.31146/1682-8658-ecg-193-9-102-108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Несмотря на крайне высокую степень инфицированности Helicobacter pylori в популяции Homo sapiens, подавляющее большинство инфицированных являются бессимптомными носителями. Широкое распространение инфекции H. pylori среди лиц без признаков патологии и низкая заболеваемость при хронической колонизации слизистой оболочки желудка указывают на то, что H. pylori с большей вероятностью является условно-патогенным микроорганизмом или патобионтом. Популяционная ликвидация инфекции H. pylori существенно снизила заболеваемость инфекцией H. pylori, однако появление устойчивости к противомикробным препаратам привело к их неэффективности.
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Affiliation(s)
- E. B. Avalueva
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - M. Yu. Serkova
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation; Almazov National Medical Research Centre
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Wen J, Lau HCH, Peppelenbosch M, Yu J. Gastric Microbiota beyond H. pylori: An Emerging Critical Character in Gastric Carcinogenesis. Biomedicines 2021; 9:1680. [PMID: 34829909 PMCID: PMC8615612 DOI: 10.3390/biomedicines9111680] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 12/27/2022] Open
Abstract
Gastric cancer (GC) is one of the global leading causes of cancer death. The association between Helicobacter pylori, which is a predominant risk factor for GC, with GC development has been well-studied. Recently, accumulating evidence has demonstrated the presence of a large population of microorganisms other than H. pylori in the human stomach. Existing sequencing studies have revealed microbial compositional and functional alterations in patients with GC and highlighted a progressive shift in the gastric microbiota in gastric carcinogenesis with marked enrichments of oral or intestinal commensals. Moreover, using a combination of gastric bacterial signatures, GC patients could be significantly distinguished from patients with gastritis. These findings, therefore, emphasize the importance of a collective microbial community in gastric carcinogenesis. Here, we provide an overview of non-H. pylori gastric microbes in gastric carcinogenesis. The molecular mechanisms of gastric microbes-related carcinogenesis and potential clinical applications of gastric microbiota as biomarkers of GC are also explored.
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Affiliation(s)
- Jun Wen
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong; (J.W.); (H.C.-H.L.)
| | - Harry Cheuk-Hay Lau
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong; (J.W.); (H.C.-H.L.)
| | - Maikel Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands;
| | - Jun Yu
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong; (J.W.); (H.C.-H.L.)
- Institute of Digestive Disease, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
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Gastric Microenvironment-A Partnership between Innate Immunity and Gastric Microbiota Tricks Helicobacter pylori. J Clin Med 2021; 10:jcm10153258. [PMID: 34362042 PMCID: PMC8347153 DOI: 10.3390/jcm10153258] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/17/2021] [Accepted: 07/21/2021] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) carcinogenicity depends on three major factors: bacterial virulence constituents, environmental factors and host's genetic susceptibility. The relationship between microenvironmental factors and H. pylori virulence factors are incontestable. H. pylori infection has a major impact on both gastric and colonic microbiota. The presence of non-H. pylori bacteria within the gastric ecosystem is particularly important since they might persistently act as an antigenic stimulus or establish a partnership with H. pylori in order to augment the subsequent inflammatory responses. The gastric ecosystem, i.e., microbiota composition in children with H. pylori infection is dominated by Streptoccocus, Neisseria, Rothia and Staphylococcus. The impairment of this ecosystem enhances growth and invasion of different pathogenic bacteria, further impairing the balance between the immune system and mucosal barrier. Moreover, altered microbiota due to H. pylori infection is involved in increasing the gastric T regulatory cells response in children. Since gastric homeostasis is defined by the partnership between commensal bacteria and host's immune system, this review is focused on how pathogen recognition through toll-like receptors (TLRs-an essential class of pathogen recognition receptors-PRRs) on the surface of macrophages and dendritic cells impact the immune response in the setting of H. pylori infection. Further studies are required for delineate precise role of bacterial community features and of immune system components.
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Casu C, Mosaico G, Natoli V, Scarano A, Lorusso F, Inchingolo F. Microbiota of the Tongue and Systemic Connections: The Examination of the Tongue as an Integrated Approach in Oral Medicine. HYGIENE 2021; 1:56-68. [DOI: 10.3390/hygiene1020006] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
The tongue is able to quickly reflect the state of health or disease of the human body. Tongue inspection is an important diagnostic approach. It is a unique method that allows to explore the pathogenesis of diseases based on the guiding principles of the holistic concept that involves the observation of changes in the lining of the tongue in order to understand the physiological functions and pathological changes of the body. It is a potential method of screening and early detection of cancer. However, the subjective inspection of the tongue has a low reliability index, and therefore computerized systems of acquisition of diagnostic bioinformation have been developed to analyze the lining of the tongue. Next-generation sequencing technology is used to determine the V2–V4 hypervariable regions of 16S rRNA to study the microbiota. A lot of neoplasms are identified only at an advanced phase, while in the early stages, many subjects remain in an asymptomatic form. On the contrary, the early diagnosis is able to increase the prognosis of cancer and improve the survival rates of subjects. Evidently, it is necessary to develop new strategies in oral medicine for the early diagnosis of diseases, and the diagnosis of the tongue as a minimally invasive method is certainly one of them.
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Affiliation(s)
- Cinzia Casu
- Department of Surgical Sciences, Oral Biotechnology Laboratory (OBL), University of Cagliari, 09126 Cagliari, Italy
| | | | - Valentino Natoli
- DDS, Private Dental Practice, 72015 Fasano, Italy
- Department of Interdisciplinary Medicine, University of Medicine Aldo Moro, 70124 Bari, Italy
| | - Antonio Scarano
- Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Felice Lorusso
- Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy
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Zhou X, Ding S, Hu R. The Related Study on the Pathogenesis of Gastrointestinal Diseases in Gastrointestinal Flora and the Risk of Gastric Ulcer Carcinogenesis. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Gastrointestinal diseases are common diseases of many kinds. The pathogenesis of gastrointestinal disease has not been fully understood. In this study with gastric mucosa specimen, among the three groups of chronic gastritis, gastric ulcer, and duodenal ulcer, there were differences
of Helicobacter pylori (H. pylori), Lactobacillus, Prevotella, Clostridium, B. fragilis, and Enterobacteriaceae. There was no significant difference in Lactobacillus among chronic gastritis, gastric ulcers, and duodenal ulcers with fecal specimens, but there was a significant
difference between these three groups and the gastric cancer group. Correlation analysis showed that six kinds of flora had a negative correlation with H. pylori, procalcitonin (PCT), tumor necrosis factor α (TNF-α), cluster of differentiation 4 (CD4+),
cluster of differentiation 8 (CD8+), immunoglobulin G (IgG), and immunoglobulin M (IgM) were different in different gastrointestinal diseases, and PCT, TNF-α and CD8+ were positively correlated with H. pylori and negatively correlated with CD4+,
IgM and IgG. Logistic regression analysis showed that age, recurrent gastric ulcer times, atrophic gastritis, and H. pylori were independent risk factors of gastric ulcer canceration. Therefore, we believe that gastrointestinal flora, especially H. pylori, plays a vital role
in the pathogenesis of gastrointestinal diseases, and H. pylori is an essential risk factor for gastric ulcer carcinogenesis.
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Affiliation(s)
- Xiaomin Zhou
- Department of Gastroenterology & Hepatology, Shanghai Jinshan District Tinglin Hospital, Shanghai 201505, PR China
| | - Songze Ding
- Department of Gastroenterology & Hepatology, Henan Provincial People’s Hospital, People’s Hospital ofZhengzhou University, Zhengzhou 450003, Henan, PR China
| | - Ruobing Hu
- Department of Gastroenterology & Hepatology, Henan Provincial People’s Hospital, People’s Hospital ofZhengzhou University, Zhengzhou 450003, Henan, PR China
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Maiti KS, Apolonski A. Monitoring the Reaction of the Body State to Antibiotic Treatment against Helicobacter pylori via Infrared Spectroscopy: A Case Study. Molecules 2021; 26:molecules26113474. [PMID: 34200454 PMCID: PMC8201021 DOI: 10.3390/molecules26113474] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 05/20/2021] [Accepted: 06/05/2021] [Indexed: 12/20/2022] Open
Abstract
The current understanding of deviations of human microbiota caused by antibiotic treatment is poor. In an attempt to improve it, a proof-of-principle spectroscopic study of the breath of one volunteer affected by a course of antibiotics for Helicobacter pylori eradication was performed. Fourier transform spectroscopy enabled searching for the absorption spectral structures sensitive to the treatment in the entire mid-infrared region. Two spectral ranges were found where the corresponding structures strongly correlated with the beginning and end of the treatment. The structures were identified as methyl ester of butyric acid and ethyl ester of pyruvic acid. Both acids generated by bacteria in the gut are involved in fundamental processes of human metabolism. Being confirmed by other studies, measurement of the methyl butyrate deviation could be a promising way for monitoring acute gastritis and anti-Helicobacter pylori antibiotic treatment.
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Affiliation(s)
- Kiran Sankar Maiti
- Max Planck Institute for Quantum Optics, Hans-Kopfermann-Strasse 1, 85748 Garching, Germany;
- Department of Experimental Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Am Coulombwall 1, 85748 Garching, Germany
| | - Alexander Apolonski
- Max Planck Institute for Quantum Optics, Hans-Kopfermann-Strasse 1, 85748 Garching, Germany;
- Department of Experimental Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Am Coulombwall 1, 85748 Garching, Germany
- Institute of Automation and Electrometry SB RAS, 630090 Novosibirsk, Russia
- Department of Physics, Novosibirsk State University, 630090 Novosibirsk, Russia
- Correspondence:
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Serrano C, Harris PR, Smith PD, Bimczok D. Interactions between H. pylori and the Gastric Microbiome: Impact on Gastric Homeostasis and Disease. CURRENT OPINION IN PHYSIOLOGY 2021; 21:57-64. [PMID: 34113748 PMCID: PMC8186273 DOI: 10.1016/j.cophys.2021.04.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Like many seemingly inhospitable environments on our planet, the highly acidic human stomach harbors a diverse bacterial microflora. The best-known member of the human gastric flora, Helicobacter pylori, causes a number of gastric diseases, including peptic ulcer disease and gastric adenocarcinoma. In the absence of Helicobacter pylori infection, the gastric microbiota displays some features similar to the oral cavity with Firmicutes the most common phylum, followed by Proteobacteria and Bacteroidetes. When present, H. pylori dominates the gastric microbiome and reduces diversity and composition of other taxa. The composition of the gastric microbiome also is altered in the setting of proton pump inhibitor therapy and gastric neoplasia. This review summarizes foundational and recent studies that have investigated the composition of the human gastric microbiome in a variety of patient groups, with a focus on potential mechanisms involved in regulation of gastric microbial community structure.
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Affiliation(s)
- Carolina Serrano
- Department of Pediatric Gastroenterology and Nutrition, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Paul R. Harris
- Department of Pediatric Gastroenterology and Nutrition, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Phillip D. Smith
- Department of Medicine, Division of Gastroenterology, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Diane Bimczok
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717
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Yarmohammadi M, Yadegar A, Ebrahimi MT, Zali MR. Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells. Probiotics Antimicrob Proteins 2021; 13:751-764. [PMID: 33206342 DOI: 10.1007/s12602-020-09721-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2020] [Indexed: 12/20/2022]
Abstract
In the present study, we aimed to investigate the modulatory effects of a potential probiotic bacterium Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-induced inflammatory response and gene expression in human gastric adenocarcinoma (AGS) cell line. The gastric epithelial cells were coinfected with a collection of H. pylori clinical strains alone or in combination with L. gasseri at a multiplicity of infection (MOI) of 1:100 for each bacterium, and incubated for different time points of 3, 6, and 12 h. IL-8 secretion from coinfected AGS cells after incubation at each time point was measured by an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-8, Bcl-2, β-catenin, integrin α5, and integrin β1 genes was determined by quantitative RT-PCR amplification of total RNA extracted from coinfected epithelial cells. L. gasseri significantly (P < 0.05 and P < 0.01) decreased the production of IL-8 in AGS cells coinfected with H. pylori strains at 6 h post-infection. We also detected that L. gasseri significantly (P < 0.05) down-regulated the gene expression level of IL-8 in H. pylori-stimulated AGS cells after 6 and 12 h of coinfection. Similarly, L. gasseri caused a significant decrease (P < 0.05) in mRNA expression of Bcl-2, β-catenin, integrin α5, and integrin β1 genes in AGS cells at 3 and 6 h after infection with H. pylori strains as compared with non-infected control cells. In conclusion, our results demonstrated that L. gasseri ameliorates H. pylori-induced inflammation and could be developed as a supplementation to the current treatment regimens administrated against H. pylori infection.
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Affiliation(s)
- Mahdieh Yarmohammadi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Tajabadi Ebrahimi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Jiang Y, Meng F, Liu Y, Zheng L, Ye S, Zhang J. Does Helicobacter pylori infection affect the structure of bacteria in the gastric mucosa and fluid in patients with chronic antral gastritis? J GEN APPL MICROBIOL 2021; 67:179-185. [PMID: 34053980 DOI: 10.2323/jgam.2020.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
This study aimed to evaluate the composition of the gastric microbiota in the gastric mucosa and gastric fluid of patients with chronic antral gastritis. Specifically, we sought to determine whether Helicobacter pylori (Hp) infection changes the bacterial community in the gastric mucosa or alters the microbiota in the gastric fluid. The bacterial community at another site in the stomach was also investigated. DNA was extracted from 160 samples collected from 40 patients with chronic antral gastritis (20 Hp-positive and 20 Hp-negative cases). Three tissue samples of the gastric mucosa (gastric angle, body, and antral mucosa) and one tube of gastric fluid were collected from every patient. A 16S rRNA amplification library was created, and high-throughput sequencing was performed. A profile of the community composition was obtained using bioinformatics methods, including cluster, taxonomy, and diversity analyses. Analysis of the gastric bacterial community revealed that the community compositions of the gastric mucosa and gastric fluid of patients without Hp are similar to but show differences from those of Hp-positive patients. The microbiota in Hp-positive patients exhibited reduced microbial diversity, and the gastric fluid of these patients contained a small proportion of Hp. The richness of Leptotrichia in mucosal samples was greater than that in gastric fluid samples from Hp-negative patients with chronic antral gastritis. Hp changes the growth of other microbiota in the mucosa and affects the microbiota in the gastric fluid of patients with chronic antral gastritis. In addition to Hp, the presence of other bacteria might be related to the development of chronic antral gastritis.
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Affiliation(s)
- Yang Jiang
- Department of Science and Education, Tongde Hospital of Zhejiang Province
| | - Fei Meng
- Department of Research service, Zhiyuan Medical Inspection Institute CO., LTD
| | - Ying Liu
- Department of Basic Sciences, Zhejiang Tongji Vocational College of Science and Technology
| | - Liyun Zheng
- Department of Research service, Zhiyuan Medical Inspection Institute CO., LTD
| | - Shufang Ye
- Department of Gastroenterology, People's Hospital of Lishui City
| | - Jianmei Zhang
- Department of Gastroenterology, People's Hospital of Lishui City
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Utembe W, Kamng'ona AW. Gut microbiota-mediated pesticide toxicity in humans: Methodological issues and challenges in the risk assessment of pesticides. CHEMOSPHERE 2021; 271:129817. [PMID: 33736210 DOI: 10.1016/j.chemosphere.2021.129817] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/20/2021] [Accepted: 01/25/2021] [Indexed: 06/12/2023]
Abstract
Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.
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Affiliation(s)
- Wells Utembe
- Toxicology Department, National Institute for Occupational Health (a division of the National Health Laboratory Service), Johannesburg, 2000, South Africa; Department of Environmental Heath, Faculty of Health Sciences, University of Johannesburg, Johannesburg, 2000, South Africa.
| | - Arox Wadson Kamng'ona
- Department of Biomedical Sciences, College of Medicine, University Of Malawi, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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Chen CC, Liou JM, Lee YC, Hong TC, El-Omar EM, Wu MS. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes 2021; 13:1-22. [PMID: 33938378 PMCID: PMC8096336 DOI: 10.1080/19490976.2021.1909459] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 03/10/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
The complex population of microbes in the human gastrointestinal (GI) tract interacts with itself and with the host, exerting a deep influence on health and disease development. The development of modern sequencing technology has enabled us to gain insight into GI microbes. Helicobacter pylori colonization significantly affects the gastric microenvironment, which in turn affects gastric microbiota and may be correlated with colonic microbiota changes. Crosstalk between H. pylori and GI commensal flora may play a role in H. pylori-related carcinogenicity and extragastric manifestations. We review current knowledge on how H. pylori shapes GI microbiota with a specific focus on its impact on the stomach and colon. We also review current evidence on colonic microbiota changes attributed to eradication therapy based on the clinical studies performed to date.
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Affiliation(s)
- Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chia Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzu-Chan Hong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Emad M El-Omar
- Microbiome Research Centre, St George & Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Chen Y, Huang J, Xu C. Lipopolysaccharide-induced DC-SIGN/TLR4 crosstalk activates NLRP3 inflammasomes via MyD88-independent signaling in gastric epithelial cells. Exp Cell Res 2020; 396:112292. [PMID: 32961144 DOI: 10.1016/j.yexcr.2020.112292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 09/03/2020] [Accepted: 09/15/2020] [Indexed: 12/28/2022]
Abstract
Abnormal pattern recognition receptor (PRR) signaling plays an important role in gastric mucosal damage caused by stomach microbiota; however, the underlying molecular mechanisms remain obscure. Here, we show that DC-SIGN, a surface phenotype marker of dendritic cells, is overexpressed in gastric epithelial cells facing LPS stimulation. NLRP3 expression in gastric epithelial cells are significantly increased and related to the degree of LPS stimulation. Furthermore, DC-SIGN could interact with TLR4, promote NLRP3 and related genes expression via MyD88-independent signaling pathway and regulate the secretion of IL-1β and IL-18 in gastric epithelial cells. The results of flow cytometry analysis show that DC-SIGN primarily mediates Th1 differentiation when co-cultured with gastric epithelial cells. These results reveal that LPS-induced DC-SIGN expression modulates NLRP3 inflammasomes formation via MyD88-independent TLR4 signaling in gastric epithelial cell, and induces a Th1-predominant host immune response,these findings may indicate a new function of DC-SIGN in non-immune cells, and elucidate the diversity role of gastric epithelial cells in mechanism of immune damage caused by microbial flora.
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Affiliation(s)
- Yufan Chen
- Department of Pediatric Neurosurgery, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Jiebin Huang
- Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Rd. II, Shanghai, 200025, China
| | - Chundi Xu
- Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Rd. II, Shanghai, 200025, China.
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Stomach microbiota, Helicobacter pylori, and group 2 innate lymphoid cells. Exp Mol Med 2020; 52:1377-1382. [PMID: 32908209 PMCID: PMC8080604 DOI: 10.1038/s12276-020-00485-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/25/2020] [Accepted: 07/06/2020] [Indexed: 12/11/2022] Open
Abstract
The stomach has been thought to host few commensal bacteria because of the existence of barriers, such as gastric acid. However, recent culture-independent, sequencing-based microbial analysis has shown that the stomach also harbors a wide diversity of microbiota. Although the stomach immune system, especially innate lymphoid cells (ILCs), has not been well elucidated, recent studies have shown that group 2 ILCs (ILC2s) are the dominant subtype in the stomach of both humans and mice. Stomach ILC2s are unique in that their existence is dependent on stomach microbiota, in sharp contrast to the lack of an impact of commensal microbiota on ILC2s in other tissues. The microbiota dependency of stomach ILC2s is partly explained by their responsiveness to interleukin (IL)-7. Stomach ILC2s express significantly higher IL-7 receptor protein levels on their surface and proliferate more in response to IL-7 stimulation in vitro than small intestinal ILC2s. Consistently, the stomach expresses much higher IL-7 protein levels than the small intestine. IL-5 secreted from stomach ILC2s promotes immunoglobulin (Ig) A production by plasma B cells. In a murine model, stomach ILC2s are important in containing Helicobacter pylori infection, especially in the early phase of infection, by promoting IgA production.
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Mohamed AA, Moussa S, Shaheen MM, Abd-Elsalam S, Ahmed R, Mostafa SM, Fouad A, Alegaily HS, Megahed SA, Abo-Amer YE. Association Between Vitamin D Receptor Gene Polymorphisms and Helicobacter Pylori Infection. THE OPEN BIOMARKERS JOURNAL 2020; 10:8-14. [DOI: 10.2174/1875318302010010008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 01/13/2020] [Accepted: 01/28/2020] [Indexed: 09/01/2023]
Abstract
Background & Aims:
Human genetic polymorphism has been reported in the susceptibility and clinical development of infection. In this regard, this study aimed to investigate the link between Vitamin D Receptor (VDR) gene polymorphism and H. pylori infection.
Materials and Methods:
This cross-sectional study was conducted on 224 adult patients with upper gastrointestinal symptoms who underwent an upper gastrointestinal endoscopy between July 2017 and May 2019 in two major university hospitals. All patients were evaluated for helicobacter pylori infection. Two gastric antral biopsy specimens were taken from each patient. One of those Biopsy specimens was evaluated for histopathology examination and the other one was immersed in a saline solution ready for genomic DNA extraction.
Results:
There were statistically significant differences between different genotypes of VDR rs7975232 polymorphism between H. pylori infected and non-infected groups (CC was higher in H. pylori negative and AC and AA were the most common in H. pylori positive group). There were statistical differences between different genotypes of VDR rs2228570 between H. pylori infected and non-infected groups (TT was higher in H. pylori negative and CT and CC were the most common in H. pylori positive group). Regarding VDR rs 7975232 gene polymorphisms; the (A) allele was significantly higher H. pylori infected, while (C) allele was significantly higher in uninfected patients. Regarding VDR rs 2228570 gene polymorphisms; the (C) allele was significantly higher H. pylori infected, while (T) allele was significantly higher in uninfected patients.
Conclusion:
There is a possible association between the FokI and Apal VDR polymorphism and H. pylori infection.
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Li BZ, Zhou HY, Guo B, Chen WJ, Tao JH, Cao NW, Chu XJ, Meng X. Dysbiosis of oral microbiota is associated with systemic lupus erythematosus. Arch Oral Biol 2020; 113:104708. [PMID: 32203722 DOI: 10.1016/j.archoralbio.2020.104708] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 02/10/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The important role of intestinal microbiota in systemic lupus erythematosus (SLE) has been recognized. Oral-gut microbiome axis is a crucial link in human health and disease, but few researches indicated the relationship between oral microorganisms and SLE. This study mainly explored the composition and changes of oral microorganisms in SLE patients with different stages, clinical manifestations and biomarkers. DESIGN Oral microbiota was detected by 16S ribosomal RNA gene sequencing from 20 SLE patients and 19 healthy controls (HCs). The evenness, diversity and composition of oral microbiota were analyzed. Moreover, receiver-operating characteristic analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. RESULTS The oral microbiota of SLE patients was imbalanced and the diversity was decreased, but no difference was found between new-onset and treated SLE patients. Families Lactobacillaceae, Veillonellaceae and Moraxellaceae were enriched in SLE patients. Families like Corynebacteriaceae, Micrococcaceae, Defluviitaleaceae, Caulobacteraceae, Phyllobacteriaceae, Methylobacteriaceae, Hyphomicrobiaceae, Sphingomonadaceae, Halomonadaceae, Pseudomonadaceae, Xanthomonadaceae, etc. were decreased in SLE patients. After multiple testing adjustment, families Sphingomonadaceae, Halomonadaceae, and Xanthomonadaceae were significantly decreased in SLE patients. And area under the curve was 0.953 (95% confidence intervals 0.890-1.000) to distinguish SLE patients from HCs. There were differences in metabolic pathways between SLE and HCs (P = 0.025). CONCLUSIONS These findings collectively support that oral microbiota dysbiosis and aberrant metabolic pathways were observed in patients with SLE. Our findings may provide suggestive evidences for the diagnosis and treatment of SLE.
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Affiliation(s)
- Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China.
| | - Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Biao Guo
- Department of Human Resource, The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China
| | - Wen-Jun Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Jin-Hui Tao
- Department of Rheumatology & Immunology, Anhui Provincial Hospital, Anhui, Hefei, China
| | - Nv-Wei Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Xiu-Jie Chu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, Anhui, China
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Rajilic-Stojanovic M, Figueiredo C, Smet A, Hansen R, Kupcinskas J, Rokkas T, Andersen L, Machado JC, Ianiro G, Gasbarrini A, Leja M, Gisbert JP, Hold GL. Systematic review: gastric microbiota in health and disease. Aliment Pharmacol Ther 2020; 51:582-602. [PMID: 32056247 DOI: 10.1111/apt.15650] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/09/2020] [Accepted: 01/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is the most infamous constituent of the gastric microbiota and its presence is the strongest risk factor for gastric cancer and other gastroduodenal diseases. Although historically the healthy stomach was considered a sterile organ, we now know it is colonised with a complex microbiota. However, its role in health and disease is not well understood. AIM To systematically explore the literature on the gastric microbiota in health and disease as well as the gut microbiota after bariatric surgery. METHODS A systematic search of online bibliographic databases MEDLINE/EMBASE was performed between 1966 and February 2019 with screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomised controlled trials, cohort studies and observational studies were included if they reported next-generation sequencing derived microbiota analysis on gastric aspirate/tissue or stool samples (bariatric surgical outcomes). RESULTS Sixty-five papers were eligible for inclusion. With the exception of H pylori-induced conditions, overarching gastric microbiota signatures of health or disease could not be determined. Gastric carcinogenesis induces a progressively altered microbiota with an enrichment of oral and intestinal taxa as well as significant changes in host gastric mucin expression. Proton pump inhibitors usage increases gastric microbiota richness. Bariatric surgery is associated with an increase in potentially pathogenic proteobacterial species in patient stool samples. CONCLUSION While H pylori remains the single most important risk factor for gastric disease, its capacity to shape the collective gastric microbiota remains to be fully elucidated. Further studies are needed to explore the intricate host/microbial and microbial/microbial interplay.
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Chouhan D, Barani Devi T, Chattopadhyay S, Dharmaseelan S, Nair GB, Devadas K, Radhakrishna Pillai M. Mycobacterium abscessus infection in the stomach of patients with various gastric symptoms. PLoS Negl Trop Dis 2019; 13:e0007799. [PMID: 31682611 PMCID: PMC6855505 DOI: 10.1371/journal.pntd.0007799] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 11/14/2019] [Accepted: 09/19/2019] [Indexed: 12/17/2022] Open
Abstract
Development of gastric diseases such as gastritis, peptic ulcer and gastric cancer is often associated with several biotic and abiotic factors. Helicobacter pylori infection is such a well-known biotic factor. However, not all H. pylori-infected individuals develop gastric diseases and not all individuals with gastric diseases are infected with H. pylori. Therefore, it is possible that other gastric bacteria may contribute to the formation and progression of gastric disease. The aim of this study was to isolate prevalent gastric bacteria under microaerobic condition and identify them by 16S rRNA gene sequence analysis. Analysis of gastric biopsies showed infection of Mycobacterium abscessus (phylum Actinobacteria) to be highly prevalent in the stomachs of subjects included. Our data show that of 129 (67 male and 62 female) patients with gastric symptoms, 96 (51 male and 45 female) showed the presence of M. abscessus in stomach tissues. Infection of M. abscessus in gastric epithelium was further confirmed by imaging with acid fast staining, immunohistochemistry and immunofluorescence. Our imaging data strongly suggested that M. abscessus is an intracellular colonizer residing inside the gastric epithelial cells rather than in macrophages. Additionally, phylogenetic analysis of the mycobacterial hsp65 gene showed that the nearest match to the M. abscessus strains isolated from our study subjects is the M. abscessus strain ATCC 19977. Surprisingly, the subjects studied, the prevalence of M. abscessus infection in stomach is even higher than the prevalence of H. pylori infection. This, to the best of our knowledge, is the first study showing the colonization of M. abscessus in human gastric mucosa among patients with various gastric symptoms. This study could provide usher in a new opportunity to understand the role of less studied gastric bacteria in the development of gastric diseases.
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Affiliation(s)
- Deepak Chouhan
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- Manipal Academy of Higher Education (MAHE), Manipal, India
| | - T. Barani Devi
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Santanu Chattopadhyay
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Sanjai Dharmaseelan
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Gopinath Balakrish Nair
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Thiruvananthapuram, India
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50
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Kreuder AJ, Lashley V, Yaeger M, Schleining JA, Plummer PJ. Histopathology and Spatial Distribution of Putative Growth Factors in Relation to Bacterial Localization of Campylobacter jejuni Within the Ovine Gallbladder. Front Vet Sci 2019; 6:226. [PMID: 31355215 PMCID: PMC6640310 DOI: 10.3389/fvets.2019.00226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 06/24/2019] [Indexed: 11/24/2022] Open
Abstract
Campylobacter jejuni is an important zoonotic pathogen that is the leading cause of both human foodborne bacterial gastroenteritis worldwide and ovine abortion in the United States. Previous studies have demonstrated that the gallbladder of ruminants is often positive on culture for Campylobacter sp., suggesting that this environment may serve as a chronic nidus of infection for maintenance of disease within populations. The objective of this study was to determine if previously identified putative growth promoting factors of C. jejuni are present within the gallbladder mucosa of sheep and to evaluate for bacterial co-localization of C. jejuni with these compounds following experimental inoculation. Direct gallbladder inoculation with C. jejuni sheep abortion (SA) clone clinical isolate IA3902 followed by immunohistochemical analysis and scanning electron microscopy allowed for identification of C. jejuni at the gallbladder mucosal surface and within the gallbladder submucosal glands. Histochemistry identified several putative Campylobacter growth promoting factors including neutral and acid mucins as well as L-fucose to be present both on the mucosal surface as well as in the gallbladder submucosal glands. In summary, following experimental inoculation of the ovine gallbladder, C. jejuni IA3902 was identified in direct contact with the gallbladder mucosal surface and deep mucosal glands in the same location as several putative growth promoting factors. This suggests the yet to be tested hypothesis that under natural conditions of infection, the gallbladder submucosal glands have the potential to provide a protected niche for chronic carriage of C. jejuni in animal hosts.
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Affiliation(s)
- Amanda J Kreuder
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.,Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Victoria Lashley
- Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Michael Yaeger
- Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Jennifer A Schleining
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Paul J Plummer
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.,Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
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