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Chen LR, Zhou SS, Yang JX, Liu XQ. Effect of hypoxia on the mucus system and intragastric microecology in the gastrointestinal tract. Microb Pathog 2025; 205:107615. [PMID: 40355054 DOI: 10.1016/j.micpath.2025.107615] [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: 10/08/2024] [Revised: 04/03/2025] [Accepted: 04/17/2025] [Indexed: 05/14/2025]
Abstract
Digestive diseases have a high incidence worldwide, with various geographic, age, and gender factors influencing the occurrence and development of the diseases. The main etiologic factors involve genetics, environment, lifestyle, and dietary habits. In a low-oxygen environment, however, the body's tissue cells activate hypoxia-inducible factor (HIF), which produces different inflammatory mediators. Hypoxia impacts health at the molecular level by modulating cellular stress responses, metabolic pathways, and immune functions. It also alters gene expression and cellular behavior, thereby affecting gastrointestinal function. Under normal physiological conditions, the gastrointestinal mucus system serves as a crucial protective barrier, defending against mechanical injury, pathogenic invasion, and exposure to harmful chemicals. The integrity and functionality of this barrier are dependent on the synthesis and regulation of mucins and mucus, which are influenced by multiple factors. Additionally, the composition and diversity of the gastric microbiota are shaped by factors such as Helicobacter pylori infection, diet, and lifestyle. A balanced gastric microbiota supports gastrointestinal health and fortifies the mucus barrier. However, hypoxia can disrupt this equilibrium, leading to inflammation, alterations in the mucus layer, and destabilization of the gastric microbiota. Understanding the interplay between hypoxia, the mucus system, and the gastric microbiota is essential for identifying novel therapeutic strategies. Future research should elucidate the mechanisms through which hypoxia influences these systems and develop interventions to mitigate its adverse effects on gastrointestinal health. We examined the impact of hypoxia on the gastrointestinal mucus system and gastric microbiota, highlighting its implications for human health and potential therapeutic approaches.
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Affiliation(s)
- Li Rong Chen
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
| | - Si Si Zhou
- Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China; Department of Gastroenterology, Qinghai Provincial People's Hospital, Xining, 810001, PR China; Qinghai Provincial Clinical Medical Research Center for Digestive Diseases, Xining, 810001, PR China.
| | - Ji Xiang Yang
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
| | - Xiao Qian Liu
- Qinghai University, Xining, 810001, PR China; Affiliated People's Hospital of Qinghai University, Xining, 810001, PR China
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2
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Wizenty J, Sigal M. Helicobacter pylori, microbiota and gastric cancer - principles of microorganism-driven carcinogenesis. Nat Rev Gastroenterol Hepatol 2025; 22:296-313. [PMID: 40011753 DOI: 10.1038/s41575-025-01042-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2025] [Indexed: 02/28/2025]
Abstract
The demonstration that Helicobacter pylori is a pathogenic bacterium with marked carcinogenic potential has paved the way for new preventive approaches for gastric cancer. Although decades of research have uncovered complex interactions of H. pylori with epithelial cells, current insights have refined our view on H. pylori-associated carcinogenesis. Specifically, the cell-type-specific effects on gastric stem and progenitor cells deep in gastric glands provide a new view on the ability of the bacteria to colonize long-term, manipulate host responses and promote gastric pathology. Furthermore, new, large-scale epidemiological data have shed light on factors that determine why only a subset of carriers progress to gastric cancer. Currently, technological advances have brought yet another revelation: H. pylori is far from the only microorganism able to colonize the stomach. Instead, the stomach is colonized by a diverse gastric microbiota, and there is emerging evidence for the occurrence and pathological effect of dysbiosis resulting from an aberrant interplay between H. pylori and the gastric mucosa. With the weight of this evidence mounting, here we consider how the lessons learned from H. pylori research inform and synergize with this emerging field to bring a more comprehensive understanding of the role of microbes in gastric carcinogenesis.
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Affiliation(s)
- Jonas Wizenty
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy and BIH Charité Clinician Scientist Program, Berlin, Germany
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
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3
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Wu J, Zhang J, Jin L, Wei X, Liu Y. Analysis of garlic intake on atrophic gastritis risk in different infectious states of Helicobacter pylori in a case-control study. Sci Rep 2025; 15:8481. [PMID: 40074793 PMCID: PMC11904234 DOI: 10.1038/s41598-025-92376-z] [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: 08/17/2024] [Accepted: 02/27/2025] [Indexed: 03/14/2025] Open
Abstract
In this case-control study, the main risk factors for atrophic gastritis (AG) were comprehensively analyzed in a real-world environment to identify potential risk factors associated with garlic intake and its effects on AG. Design Upper gastrointestinal endoscopy and pathological examination were performed as part of a gastric cancer screening and health check-up program. The detailed characteristics of both the case group and healthy control group were recorded and analyzed. All participants were fasted for at least 4 h and a urea breath test13C-UBT) was performed in all participants at rest. Both univariate and multivariate logistic regression analyses were performed and presented as the odds ratio (OR) and 95% confidential interval (CI), with additional subgroup analysis stratified by infectious state based on the presence, eradication or absence of H. pylori. Setting Gansu Province in China. Participants 10,035 people from Gansu Province in China were included. Among 7,058 participants, 4,712 (66.8%) had AG. Garlic intake was a significant risk factor for AG in participants currently (infected state) or previously (eradicated state) infected with H. pylori (OR = 1.39, 95% CI: 1.06-1.83; OR = 1.16, 95% CI = 1.01-1.32). Garlic intake was not significantly associated with AG in participants without H. pylori' s infection (OR = 1.14, 95% CI: 0.88-1.46). The association between garlic intake and AG differed by H. pylori infectious state. People in the infected or eradicated states are at a higher risk for AG associated with garlic intake. Diet may regulate the pathogenic role of H. pylori and intestinal flora.
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Affiliation(s)
- Jianjun Wu
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Leve, Lanzhou, 730000, Gansu Province, China
- Institute of Preventive Medicine of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
| | - Jia Zhang
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Leve, Lanzhou, 730000, Gansu Province, China
- Institute of Preventive Medicine of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
| | - Lan Jin
- School of Medicine, Yale University, New Haven, CT, USA
| | - Xingmin Wei
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Leve, Lanzhou, 730000, Gansu Province, China
- Institute of Preventive Medicine of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China
| | - Yuqin Liu
- Cancer Epidemiology Laboratory of Gansu Cancer Hospital, Lanzhou, 730000, Gansu Province, China.
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Ye Y, Bin B, Chen P, Chen J, Meng A, Yu L, Yang F, Cui H. Advances in the study of the role of gastric microbiota in the progression of gastric cancer. Microb Pathog 2025; 199:107240. [PMID: 39708981 DOI: 10.1016/j.micpath.2024.107240] [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: 07/10/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 12/23/2024]
Abstract
Gastric cancer (GC) is a common malignant tumor and the third most common cancer in China in terms of mortality. Stomach microorganisms play complex roles in the development of GC. The carcinogenic mechanism of Helicobacter pylori has been elucidated, and there is much evidence that other microorganisms in the gastric mucosa are also heavily involved in the disease progression of this cancer. However, their carcinogenic mechanisms have not yet been fully elucidated. The microbial compositions associated with the normal stomach, precancerous lesions, and GC are distinctly different and have a complex evolutionary mechanism. The dysregulation of gastric microbiota may play a key role in the oncogenic process from precancerous lesions to malignant gastric tumors. In this review, we explore the potential translational and clinical implications of intragastric microbes in the diagnosis, prognosis, and treatment of GC. Finally, we summarize the research dilemmas and solutions concerning intragastric microbes, emphasizing that they should be at the forefront of strategies for GC prevention and treatment.
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Affiliation(s)
- Yu Ye
- Inner Mongolia Medical University, No 60, Xi Lin Guo Le South Road, Hohhot, 010020, Inner Mongolia Autonomous Region, PR China
| | - Ba Bin
- Department of Oncology, Ordos Hospital of Traditional Chinese Medicine, No 5, Yongning Street, Kangbashi District, Ordos City, Inner Mongolia Autonomous Region, PR China
| | - Pengfei Chen
- The Affiliated Hospital of Inner Mongolia Medical University, PR China
| | - Jing Chen
- Medical Department of Ordos College of Applied Technology, PR China
| | - Aruna Meng
- Inner Mongolia Medical University, No 60, Xi Lin Guo Le South Road, Hohhot, 010020, Inner Mongolia Autonomous Region, PR China
| | - Lei Yu
- Department of Pharmacy, Traditional Chinese Medicine Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia Autonomous Region, 010020, PR China
| | - Fan Yang
- Inner Mongolia Autonomous Region Blood Central, PR China.
| | - Hongwei Cui
- Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, No 42, Zhao Wu Da Road, Hohhot, 010020, Inner Mongolia Autonomous Region, PR China.
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He Y, Gao S, Jiang L, Yang J. Changes in gut microbiota after gastric cancer surgery: a prospective longitudinal study. Front Oncol 2025; 14:1533816. [PMID: 39911821 PMCID: PMC11794085 DOI: 10.3389/fonc.2024.1533816] [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: 11/25/2024] [Accepted: 12/27/2024] [Indexed: 02/07/2025] Open
Abstract
Background This study was designed to characterize gut microbiota changes of the patients with gastric cancer before and after the gastrectomy during their hospital staying periods. Methods 16S ribosomal RNA (rRNA) gene sequencing was used to evaluate differences in gut microbiota among patients with gastric cancer before and after the gastrectomy by comparing gut microbiota α diversity, β diversity, and structure composition at different taxonomic levels. Results A total of 120 fecal specimens were collected from 60 patients. There was no significant difference in Chao1 index, Shannon index, and Simpson index before and after gastrectomy (all P > 0.05). At the phylum level, the gut microbiota in the gastrectomy group showed less abundance of Bacteroidota, Synergistota, and Verrucomicrobiota but with higher abundance of Campylobacter, Actinobacteria, and Bacillota. At the genus level, the gut microbiota in the gastrectomy group showed less abundance of flora Bacteroides, Faecalibacterium, Blautia, and Lachnospiraceae nk4a136 group but with higher abundance of Campylobacter, Porphyromona, Finegordia, Dialist, Anaerococcus, and Corynebacterium. Conclusions There was no significant change in the diversity of intestinal flora before and after surgery. However, significant changes in the structure of intestinal flora before and after surgery were occurred.
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Affiliation(s)
| | | | | | - Jie Yang
- Colorectal Cancer Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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Al-Matouq J, Al-Ghafli H, Alibrahim NN, Alsaffar N, Radwan Z, Ali MD. Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues. Cancers (Basel) 2025; 17:226. [PMID: 39858007 PMCID: PMC11763844 DOI: 10.3390/cancers17020226] [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: 11/25/2024] [Revised: 12/23/2024] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.
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Affiliation(s)
- Jenan Al-Matouq
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Hawra Al-Ghafli
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Noura N. Alibrahim
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Nida Alsaffar
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Zaheda Radwan
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Mohammad Daud Ali
- Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia;
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Giddings HJ, Teodósio A, Jones J, McMurray JL, Hunter K, Alame R, Gardiner I, Abdawn Z, Butterworth W, Henderson IR, Cole JA, Shannon‐Lowe CD, Rossiter‐Pearson AE. The Gastric Microbiota Invade the Lamina Propria in Helicobacter pylori-Associated Gastritis and Precancer. Helicobacter 2025; 30:e70016. [PMID: 40011208 PMCID: PMC11865006 DOI: 10.1111/hel.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 01/21/2025] [Accepted: 01/28/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Stomach cancer is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori is the main risk factor for gastric adenocarcinoma (GAC), yet the precise mechanism underpinning this association remains controversial. Gastric intestinal metaplasia (GIM) represents the precancerous stage and follows H. pylori-associated chronic gastritis (CG). Sequencing studies have revealed fewer H. pylori and more non-H. pylori bacteria in GAC. However, the spatial organization of the gastric microbiota in health and disease is unknown. MATERIALS AND METHODS Here, we have combined RNA in situ hybridization and immunohistochemistry to detect H. pylori, non-H. pylori bacteria, and host cell markers (E-cadherin, Mucins 5AC and 2) on tissue sections from patients with CG (n = 15) and GIM (n = 17). RESULTS Quantitative analysis of whole slide scans revealed significant correlations of H. pylori and other bacteria in CG and GIM. In contrast to sequencing studies, significantly fewer non-H. pylori bacteria were detected in H. pylori-negative patients. Importantly, whilst H. pylori exclusively colonized the gastric glands, non-H. pylori bacteria invaded the lamina propria in 6/9 CG and 8/10 GIM H. pylori-positive patients. A rapid and cost-effective modified Gram stain was used to confirm these findings and enabled detection of non-H. pylori bacteria in GIM samples. CONCLUSIONS The invasion of the gastric lamina propria by non-H. pylori bacteria during H. pylori-associated CG and GIM represents an overlooked phenomenon in cancer progression. Further work must determine the mechanisms underlying the synergistic roles of H. pylori and other bacteria in carcinogenesis. This observation should redirect attempts to prevent, diagnose, and treat GAC.
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Affiliation(s)
- Harriet J. Giddings
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Ana Teodósio
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Jordanne Jones
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Jack L. McMurray
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
- Rheumatology Research GroupUniversity of BirminghamBirminghamUK
| | - Kelly Hunter
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Riad Alame
- Queen Elizabeth HospitalUniversity Hospital Birmingham NHS Foundation TrustBirminghamUK
| | - Isaac Gardiner
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Zainab Abdawn
- Queen Elizabeth HospitalUniversity Hospital Birmingham NHS Foundation TrustBirminghamUK
| | - William Butterworth
- Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Ian R. Henderson
- Institute for Molecular BiosciencesUniversity of QueenslandBrisbaneAustralia
| | - Jeffrey A. Cole
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
| | - Claire D. Shannon‐Lowe
- Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Amanda E. Rossiter‐Pearson
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
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Doranga S, Krogfelt KA, Cohen PS, Conway T. Nutrition of Escherichia coli within the intestinal microbiome. EcoSal Plus 2024; 12:eesp00062023. [PMID: 38417452 PMCID: PMC11636361 DOI: 10.1128/ecosalplus.esp-0006-2023] [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: 05/31/2023] [Accepted: 11/03/2023] [Indexed: 03/01/2024]
Abstract
In this chapter, we update our 2004 review of "The Life of Commensal Escherichia coli in the Mammalian Intestine" (https://doi.org/10.1128/ecosalplus.8.3.1.2), with a change of title that reflects the current focus on "Nutrition of E. coli within the Intestinal Microbiome." The earlier part of the previous two decades saw incremental improvements in understanding the carbon and energy sources that E. coli and Salmonella use to support intestinal colonization. Along with these investigations of electron donors came a better understanding of the electron acceptors that support the respiration of these facultative anaerobes in the gastrointestinal tract. Hundreds of recent papers add to what was known about the nutrition of commensal and pathogenic enteric bacteria. The fact that each biotype or pathotype grows on a different subset of the available nutrients suggested a mechanism for succession of commensal colonizers and invasion by enteric pathogens. Competition for nutrients in the intestine has also come to be recognized as one basis for colonization resistance, in which colonized strain(s) prevent colonization by a challenger. In the past decade, detailed investigations of fiber- and mucin-degrading anaerobes added greatly to our understanding of how complex polysaccharides support the hundreds of intestinal microbiome species. It is now clear that facultative anaerobes, which usually cannot degrade complex polysaccharides, live in symbiosis with the anaerobic degraders. This concept led to the "restaurant hypothesis," which emphasizes that facultative bacteria, such as E. coli, colonize the intestine as members of mixed biofilms and obtain the sugars they need for growth locally through cross-feeding from polysaccharide-degrading anaerobes. Each restaurant represents an intestinal niche. Competition for those niches determines whether or not invaders are able to overcome colonization resistance and become established. Topics centered on the nutritional basis of intestinal colonization and gastrointestinal health are explored here in detail.
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Affiliation(s)
- Sudhir Doranga
- Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Karen A. Krogfelt
- Department of Science and Environment, Pandemix Center Roskilde University, Roskilde, Denmark
| | - Paul S. Cohen
- Department of Cell and Molecular Biology, University of Rhode Island, Kingston, Rhode Island, USA
| | - Tyrrell Conway
- Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, Oklahoma, USA
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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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10
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Park YS, Ahn K, Yun K, Jeong J, Baek KW, Park DJ, Han K, Ahn YJ. Effect of Helicobacter pylori on sleeve gastrectomy and gastric microbiome differences in patients with obesity and diabetes. Int J Obes (Lond) 2024; 48:1664-1672. [PMID: 39179750 PMCID: PMC11502492 DOI: 10.1038/s41366-024-01611-6] [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: 03/25/2024] [Revised: 07/29/2024] [Accepted: 08/08/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND Obesity and diabetes mellitus (DM) have become public health concerns worldwide. Both conditions have severe consequences and are associated with significant medical costs and productivity loss. Additionally, Helicobacter pylori infection may be a risk factor for the development of these conditions. However, whether eradicating H. pylori infection directly causes weight loss or improves insulin sensitivity is unknown. METHODS In this study, we confirmed the effect of sleeve gastrectomy according to the state of the gastric microbiota in 40 patients with obesity, DM, and H. pylori infection. Patients with obesity were divided into four groups: non-DM without H. pylori infection (ND), non-DM with H. pylori infection (ND-HP), DM, and DM with H. pylori infection (DM-HP) using 16S V3-V4 sequencing. RESULTS In the DM group, ALT, hemoglobin, HbA1c, blood glucose, and HSI significantly decreased, whereas high-density lipoprotein significantly increased. However, in the H. pylori-positive group, no significant difference was observed. The diversity of gastric microbiota decreased in the order of the ND > DM > ND-HP > DM-HP groups. We also conducted a correlation analysis between the preoperative microbes and clinical data. In the ND-HP group, most of the top 20 gastric microbiota were negatively correlated with glucose metabolism. However, H. pylori infection was positively correlated with pre-insulin levels. CONCLUSION Therefore, these findings indicate that patients with obesity and diabetes clearly benefit from surgery, but H. pylori infection may also affect clinical improvement.
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Affiliation(s)
- Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kung Ahn
- HuNbiome Co., Ltd, R&D Center, Gasan Digital 1-ro, Geumcheon-gu, Seoul, Korea
| | - Kyeongeui Yun
- HuNbiome Co., Ltd, R&D Center, Gasan Digital 1-ro, Geumcheon-gu, Seoul, Korea
| | - Jinuk Jeong
- Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, 31116, Korea
| | - Kyung-Wan Baek
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Kyudong Han
- Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, 31116, Korea.
- Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, 31116, Korea.
- Department of Bioconvergence Engineering, Dankook University, Yongin, 1491, Republic of Korea.
| | - Yong Ju Ahn
- HuNbiome Co., Ltd, R&D Center, Gasan Digital 1-ro, Geumcheon-gu, Seoul, Korea.
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11
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Wu M, Tian C, Zou Z, Jin M, Liu H. Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review. Cancers (Basel) 2024; 16:3547. [PMID: 39456641 PMCID: PMC11506470 DOI: 10.3390/cancers16203547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.
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Affiliation(s)
- Mengjiao Wu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (M.W.); (Z.Z.)
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chenjun Tian
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China;
| | - Zhenwei Zou
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (M.W.); (Z.Z.)
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- The Eighth Hospital of Wuhan, Wuhan 430012, China
| | - Min Jin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (M.W.); (Z.Z.)
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Hongli Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (M.W.); (Z.Z.)
- Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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12
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Kolahi Sadeghi L, Vahidian F, Eterafi M, Safarzadeh E. Gastrointestinal cancer resistance to treatment: the role of microbiota. Infect Agent Cancer 2024; 19:50. [PMID: 39369252 PMCID: PMC11453072 DOI: 10.1186/s13027-024-00605-3] [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: 06/15/2024] [Accepted: 08/20/2024] [Indexed: 10/07/2024] Open
Abstract
The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy.
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Affiliation(s)
- Leila Kolahi Sadeghi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Fatemeh Vahidian
- Faculty of Medicine, Laval University, Quebec, Canada
- Centre de Recherche de I'Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Quebec, Canada
| | - Majid Eterafi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Students' Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
- Department of Microbiology, Parasitology, and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
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13
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Ye ZN, Eslick GD, Huang SG, He XX. Faecal microbiota transplantation for eradicating Helicobacter pylori infection: clinical practice and theoretical postulation. EGASTROENTEROLOGY 2024; 2:e100099. [PMID: 39944265 PMCID: PMC11770466 DOI: 10.1136/egastro-2024-100099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 12/03/2024] [Indexed: 01/11/2025]
Abstract
The sustained increase in antibiotic resistance leads to a declining trend in the eradication rate of Helicobacter pylori (H. pylori) infection with antibiotic-based eradication regimens. Administration of a single probiotic shows limited efficacy in eradicating H. pylori infection. This review indicates that faecal microbiota transplantation (FMT), a novel therapeutic approach, either as a monotherapy or adjunctive therapy, exhibits beneficial effects in terms of the eradication of H. pylori infection and the prevention of adverse events. The role of FMT in H. pylori eradication may be associated directly or indirectly with some therapeutic constituents within the faecal suspension, including bacteria, viruses, antimicrobial peptides and metabolites. In addition, variations in donor selection, faecal suspension preparation and delivery methods are believed to be the main factors determining the effectiveness of FMT for the treatment of H. pylori infection. Future research should refine the operational procedures of FMT to achieve optimal efficacy for H. pylori infection and explore the mechanisms by which FMT acts against H. pylori.
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Affiliation(s)
- Zhi-Ning Ye
- The Affiliated Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, China
| | - Guy D Eslick
- The Australian Paediatric Surveillance Unit, The University of Sydney, The Children's Hospital, Sydney, New South Wale, Australia
| | - Shao-Gang Huang
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xing-Xiang He
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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14
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Bricca L, Porcari S, Savarino E, Rugge M. Microbiota in gastrointestinal malignancies. Best Pract Res Clin Gastroenterol 2024; 72:101953. [PMID: 39645287 DOI: 10.1016/j.bpg.2024.101953] [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: 08/02/2024] [Revised: 10/05/2024] [Accepted: 10/09/2024] [Indexed: 12/09/2024]
Abstract
This manuscript provides an overview of the microbiota profile associated with precancerous lesions in the esophagus, stomach, and large bowel. The critical review of the available data reveals significant variability in the methods used for microbiota profiling. This variability may affect the reliable identification of specific biological links between histologically profiled neoplastic diseases and the microbiota population. Overall, this critical review reveals significant links between microbiota communities and the different lesions within the spectrum of the oncogenetic cascade in various epidemiological contexts and anatomical districts.
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Affiliation(s)
- Ludovica Bricca
- Department of Surgical Oncological and Gastroenterological Science (DiSCOG), Gastroenterology Unit, University of Padova, Padova, Italy
| | - Serena Porcari
- Department of Medical and Surgical Sciences, University Cattolica del Sacro Cuore - IRCCS Policlinico A. Gemelli, Roma, Italy
| | - Edoardo Savarino
- Department of Surgical Oncological and Gastroenterological Science (DiSCOG), Gastroenterology Unit, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy.
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15
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Tohumcu E, Kaitsas F, Bricca L, Ruggeri A, Gasbarrini A, Cammarota G, Ianiro G. Helicobacter pylori and the Human Gastrointestinal Microbiota: A Multifaceted Relationship. Antibiotics (Basel) 2024; 13:584. [PMID: 39061266 PMCID: PMC11274338 DOI: 10.3390/antibiotics13070584] [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: 05/17/2024] [Revised: 06/17/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Helicobacter pylori is a type of Gram-negative bacteria belonging to the Proteobacteria phylum which is known to cause gastrointestinal disorders such as gastritis and gastric ulcers. Its treatment is based on current eradication regimens, which are composed of combinations of antibiotics such as clarithromycin, metronidazole, levofloxacin and amoxicillin, often combined with a proton pump inhibitor (PPI). With the development of sequencing technologies, it has been demonstrated that not only does the colonization of the gastric and gut environment by H. pylori cause microbial changes, but also the treatment regimens used for its eradication have a significant altering effect on both the gastric and gut microbiota. Here, we review current knowledge on microbiota modulations of current therapies in both environments. We also summarize future perspectives regarding H. pylori infection, the integration of probiotics into therapy and what challenges are being faced on a global basis when we talk about eradication.
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Affiliation(s)
- Ege Tohumcu
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Kaitsas
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Ludovica Bricca
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), Padua Univeristy, 35123 Padova, Italy;
| | - Alessandro Ruggeri
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
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16
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Mager LF, Krause T, McCoy KD. Interaction of microbiota, mucosal malignancies, and immunotherapy-Mechanistic insights. Mucosal Immunol 2024; 17:402-415. [PMID: 38521413 DOI: 10.1016/j.mucimm.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/09/2024] [Accepted: 03/17/2024] [Indexed: 03/25/2024]
Abstract
The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria. Here we aim to comprehensively summarize the current knowledge of microbiome-host immunity interactions and cancer therapy in various mucosal tissues to find commonalities and thus identify potential functionally relevant bacterial taxa. Moreover, we also review recent studies identifying specific bacteria and mechanisms through which the microbiome modulates cancer development and therapy efficacy.
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Affiliation(s)
- Lukas F Mager
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Internal Medicine I, Faculty of Medicine, University of Tübingen, Germany; M3 Research Center for Malignom, Metabolome and Microbiome, Faculty of Medicine University Tübingen, Germany
| | - Tim Krause
- Department of Internal Medicine I, Faculty of Medicine, University of Tübingen, Germany; M3 Research Center for Malignom, Metabolome and Microbiome, Faculty of Medicine University Tübingen, Germany
| | - Kathy D McCoy
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
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17
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Sgamato C, Rocco A, Compare D, Priadko K, Romano M, Nardone G. Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer. Antibiotics (Basel) 2024; 13:484. [PMID: 38927151 PMCID: PMC11201017 DOI: 10.3390/antibiotics13060484] [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: 04/26/2024] [Revised: 05/20/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients' treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.
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Affiliation(s)
- Costantino Sgamato
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Alba Rocco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Debora Compare
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
| | - Kateryna Priadko
- Hepatogastroenterology Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (K.P.); (M.R.)
| | - Marco Romano
- Hepatogastroenterology Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (K.P.); (M.R.)
| | - Gerardo Nardone
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy; (C.S.); (D.C.); (G.N.)
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18
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Santacroce L, Topi S, Bottalico L, Charitos IA, Jirillo E. Current Knowledge about Gastric Microbiota with Special Emphasis on Helicobacter pylori-Related Gastric Conditions. Curr Issues Mol Biol 2024; 46:4991-5009. [PMID: 38785567 PMCID: PMC11119845 DOI: 10.3390/cimb46050299] [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: 03/31/2024] [Revised: 05/06/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024] Open
Abstract
The gastric milieu, because of its very low acidic pH, is very harsh for bacterial growth. The discovery of Helicobacter pylori (H.p.) has opened a new avenue for studies on the gastric microbiota, thus indicating that the stomach is not a sterile environment. Nowadays, new technologies of bacterial identification have demonstrated the existence of other microorganisms in the gastric habitat, which play an important role in health and disease. This bacterium possesses an arsenal of compounds which enable its survival but, at the same time, damage the gastric mucosa. Toxins, such as cytotoxin-associated gene A, vacuolar cytotoxin A, lipopolysaccharides, and adhesins, determine an inflammatory status of the gastric mucosa which may become chronic, ultimately leading to a gastric carcinoma. In the initial stage, H.p. persistence alters the gastric microbiota with a condition of dysbiosis, predisposing to inflammation. Probiotics and prebiotics exhibit beneficial effects on H.p. infection, and, among them, anti-inflammatory, antioxidant, and antibacterial activities are the major ones. Moreover, the association of probiotics with prebiotics (synbiotics) to conventional anti-H.p. therapy contributes to a more efficacious eradication of the bacterium. Also, polyphenols, largely present in the vegetal kingdom, have been demonstrated to alleviate H.p.-dependent pathologies, even including the inhibition of tumorigenesis. The gastric microbiota composition in health and disease is described. Then, cellular and molecular mechanisms of H.p.-mediated damage are clarified. Finally, the use of probiotics, prebiotics, and polyphenols in experimental models and in patients infected with H.p. is discussed.
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Affiliation(s)
- Luigi Santacroce
- Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari ‘Aldo Moro’, 70124 Bari, Italy;
| | - Skender Topi
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania; (S.T.)
| | - Lucrezia Bottalico
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania; (S.T.)
| | - Ioannis Alexandros Charitos
- Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, Institute of Bari, 70124 Bari, Italy;
| | - Emilio Jirillo
- Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari ‘Aldo Moro’, 70124 Bari, Italy;
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19
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Yang XT, Niu PQ, Li XF, Sun MM, Wei W, Chen YQ, Zheng JY. Differential cytokine expression in gastric tissues highlights helicobacter pylori's role in gastritis. Sci Rep 2024; 14:7683. [PMID: 38561502 PMCID: PMC10984929 DOI: 10.1038/s41598-024-58407-x] [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: 03/27/2023] [Accepted: 03/28/2024] [Indexed: 04/04/2024] Open
Abstract
Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1β, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1β, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.
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Affiliation(s)
- Xing-Tang Yang
- Department of Gastroenterology, Chongming Branch, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 66 Xiangyangdong Road, Bao Town, Chongming District, Shanghai, 202157, People's Republic of China.
- Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.
| | - Pei-Qin Niu
- Department of Gastroenterology, Chongming Branch, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 66 Xiangyangdong Road, Bao Town, Chongming District, Shanghai, 202157, People's Republic of China.
| | - Xiao-Feng Li
- Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China
| | - Ming-Ming Sun
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China
| | - Wei Wei
- Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China
| | - Yan-Qing Chen
- Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China
| | - Jia-Yi Zheng
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China
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20
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Yu YY, Wu LY, Sun X, Gu Q, Zhou QQ. Effect of Lactobacillus plantarum ZFM4 in Helicobacter pylori-infected C57BL/6 mice: prevention is better than cure. Front Cell Infect Microbiol 2024; 13:1320819. [PMID: 38235493 PMCID: PMC10791759 DOI: 10.3389/fcimb.2023.1320819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/12/2023] [Indexed: 01/19/2024] Open
Abstract
Objectives This study was performed to explore the preventive and therapeutic effects of Lactobacillus plantarum ZFM4 on H. pylori infections of the stomach tissue in C57BL/6 mice. Methods In this study, 40 specific-pathogen-free female C57BL/6 mice were randomly divided into five groups, namely, the control, ZFM4 pretreatment) ZFM4 pretreatment before H. pylori infected), model (H. pylori infected), triple therapy (H. pylori infected and treated with triple therapy), and ZFM4 treatment groups (H. pylori infected and treated with ZFM4). The preventive and therapeutic effects of Lactobacillus plantarum ZFM4 were evaluated in H. pylori-infected C57BL/6 mice by assessing gastric tissue morphology, inflammatory cytokine levels, microbial composition, and microbial diversity. Results Lactobacillus plantarum ZFM4 was able to survive in low gastric pH and play a role in preventing H. pylori infection. This was evident from a reduction in both, the gastric inflammatory response and expression of inflammatory factors caused by H. pylori infection. Lactobacillus plantarum ZFM4 could also inhibit the growth of H. pylori via its beneficial impact on the gastric microbiota. Conclusion Our findings suggest that Lactobacillus plantarum ZFM4 offers superior preventive effects against H. pylori infections when used alone. However, the therapeutic effect on established infections is weaker. Further clinical trials are needed to confirm the specific dosage, duration, and other aspects of administration.
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Affiliation(s)
- Ying-ying Yu
- Department of general practice, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Ling-yan Wu
- Department of general practice, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xue Sun
- Department of general practice, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Qing-qing Zhou
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
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21
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Gao S, Zhang Z, Sun K, Li MX, Qi YJ. Upper gastrointestinal tract microbiota with oral origin in relation to oesophageal squamous cell carcinoma. Ann Med 2023; 55:2295401. [PMID: 38151037 PMCID: PMC10763922 DOI: 10.1080/07853890.2023.2295401] [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: 07/24/2023] [Accepted: 12/12/2023] [Indexed: 12/29/2023] Open
Abstract
Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review.Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm.Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the "Oesophageal Cancer Belt". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies.Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC.
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Affiliation(s)
- Shegan Gao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Zichao Zhang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Kui Sun
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Meng-Xiang Li
- Department of Mathematics and Physics, Luoyang Institute of Science and Technology, Luoyang, China
| | - Yi-Jun Qi
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
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22
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Gomez-Ramirez U, Nolasco-Romero CG, Contreras-Rodríguez A, Zuñiga G, Mendoza-Elizalde S, Prado-Galbarro FJ, Pérez Aguilar F, Pedraza Tinoco JE, Valencia-Mayoral P, Velázquez-Guadarrama N. Dysbiosis by Eradication of Helicobacter pylori Infection Associated with Follicular Gastropathy and Pangastropathy. Microorganisms 2023; 11:2748. [PMID: 38004759 PMCID: PMC10673246 DOI: 10.3390/microorganisms11112748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/03/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
Dysbiosis plays an important role in the development of bacterial infections in the gastric mucosa, particularly Helicobacter pylori. The international guidelines for the treatment of H. pylori infections suggest standard triple therapy (STT). Nevertheless, because of the increasing resistance rates to clarithromycin, metronidazole has been widely considered in several countries. Unfortunately, the non-justified administration of antibiotics induces dysbiosis in the target organ. We characterized the gastric microbiota of patients diagnosed with follicular gastropathy and pangastropathy attributed to H. pylori infection, before and after the administration of STT with metronidazole. Dominant relative abundances of Cutibacterium were observed in pre-treatment patients, whereas H. pylori was observed at <11%, suggesting the multifactor property of the disease. The correlation of Cutibacterium acnes and H. pylori with gastric infectious diseases was also evaluated using quantitative real-time polymerase chain reaction. The dominance of C. acnes over H. pylori was observed in gastritis, gastropathies, and non-significant histological alterations. None of the microorganisms were detected in the intestinal metaplasia. Post-treatment alterations revealed an increase in the relative abundances of Staphylococcus, Pseudomonas, and Klebsiella. Non-H. pylori gastrointestinal bacteria can be associated with the initiation and development of gastric diseases, such as pathobiont C. acnes.
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Affiliation(s)
- Uriel Gomez-Ramirez
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (C.G.N.-R.); (S.M.-E.)
- Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Carolina G. Nolasco-Romero
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (C.G.N.-R.); (S.M.-E.)
- Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Araceli Contreras-Rodríguez
- Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Gerardo Zuñiga
- Laboratorio de Variación Biológica y Evolución, Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Sandra Mendoza-Elizalde
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (C.G.N.-R.); (S.M.-E.)
| | | | - Fernando Pérez Aguilar
- Servicio de Endoscopía Gastrointestinal, Hospital General Dr. Fernando Quiroz, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City 01140, Mexico;
| | | | - Pedro Valencia-Mayoral
- Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
| | - Norma Velázquez-Guadarrama
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (C.G.N.-R.); (S.M.-E.)
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23
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Chattopadhyay I, Gundamaraju R, Rajeev A. Diversification and deleterious role of microbiome in gastric cancer. Cancer Rep (Hoboken) 2023; 6:e1878. [PMID: 37530125 PMCID: PMC10644335 DOI: 10.1002/cnr2.1878] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/20/2023] [Accepted: 07/22/2023] [Indexed: 08/03/2023] Open
Abstract
Gut microbiota dictates the fate of several diseases, including cancer. Most gastric cancers (GC) belong to gastric adenocarcinomas (GAC). Helicobacter pylori colonizes the gastric epithelium and is the causative agent of 75% of all stomach malignancies globally. This bacterium has several virulence factors, including cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), and outer membrane proteins (OMPs), all of which have been linked to the development of gastric cancer. In addition, bacteria such as Escherichia coli, Streptococcus, Clostridium, Haemophilus, Veillonella, Staphylococcus, and Lactobacillus play an important role in the development of gastric cancer. Besides, lactic acid bacteria (LAB) such as Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus were found in greater abundance in GAC patients. To identify potential diagnostic and therapeutic interventions for GC, it is essential to understand the mechanistic role of H. pylori and other bacteria that contribute to gastric carcinogenesis. Furthermore, understanding bacteria-host interactions and bacteria-induced inflammatory pathways in the host is critical for developing treatment targets for gastric cancer.
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Affiliation(s)
| | - Rohit Gundamaraju
- ER stress and Mucosal Immunology TeamSchool of Health Sciences, University of TasmaniaLauncestonTasmaniaAustralia
| | - Ashwin Rajeev
- Department of BiotechnologyCentral University of Tamil NaduThiruvarurIndia
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24
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Sharma P, Phatak SM, Warikoo P, Mathur A, Mahant S, Das K, Das R. Crosstalk between Helicobacter pylori and gastrointestinal microbiota in various gastroduodenal diseases-A systematic review. 3 Biotech 2023; 13:303. [PMID: 37588796 PMCID: PMC10425313 DOI: 10.1007/s13205-023-03734-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 07/21/2023] [Indexed: 08/18/2023] Open
Abstract
Gastroduodenal diseases have prevailed for a long time and more so due to dominance of gut bacteria Helicobacter pylori in most of the cases. But habitation by other gut microbiota in gastroduodenal diseases and the relationship between Helicobacter pylori and gastrointestinal microbiota in different gastroduodenal diseases is somewhat being unravelled in the current times. For this systematic review, we did a literature search of various gastroduodenal diseases and the effect on gut microbiota pertaining to it. A search of the online bibliographic databases PUBMED and PUBMED CENTRAL was carried out to identify articles published between 1977 and May 2022. The analysis of these selected studies highlighted the inhabitation of other gut microbiota such as Fusobacteria, Bacteroidetes, Streptococcaceae, Prevotellaceae, Fusobacteriaceae, and many others. Interplay between these microbiota and H. pylori have also been noted which suggested that gastroduodenal diseases and gut microbiota are intertwined by a symbiotic association regardless of the H. pylori status. The relationship between the gut microbiota and many gastroduodenal diseases, such as gastritis, gastric cancer, lymphomas, and ulcers, demonstrates the dysbiosis of the gut microbiota in both the presence and absence of H. pylori. The evolving ways for eliminating H. pylori are provided along with inhibiting qualities of other species on H. pylori. Most significant member of our gut system is Helicobacter pylori which has been associated with numerous diseases like gastric cancer, gastritis, duodenal ulcer.
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Affiliation(s)
- Prateek Sharma
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
| | - Shravani M. Phatak
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
| | - Prisha Warikoo
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
| | - Akshita Mathur
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
| | - Shweta Mahant
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
| | - Kunal Das
- Department of Gastroenterology, Yashoda Super Speciality Hospital, Kaushambi, Ghaziabad, Uttar Pradesh India
| | - Rajashree Das
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, U.P. India
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25
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Huang H, Zhong W, Wang X, Yang Y, Wu T, Chen R, Liu Y, He F, Li J. The role of gastric microecological dysbiosis in gastric carcinogenesis. Front Microbiol 2023; 14:1218395. [PMID: 37583514 PMCID: PMC10423824 DOI: 10.3389/fmicb.2023.1218395] [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: 05/07/2023] [Accepted: 07/10/2023] [Indexed: 08/17/2023] Open
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and reducing its mortality has become an urgent public health issue. Gastric microecological dysbiosis (including bacteria, fungi, viruses, acid suppressants, antibiotics, and surgery) can lead to gastric immune dysfunction or result in a decrease in dominant bacteria and an increase in the number and virulence of pathogenic microorganisms, which in turn promotes development of GC. This review analyzes the relationship between gastric microecological dysbiosis and GC, elucidates dynamic alterations of the microbiota in Correa's cascade, and identifies certain specific microorganisms as potential biomarkers of GC to aid in early screening and diagnosis. In addition, this paper presents the potential of gastric microbiota transplantation as a therapeutic target for gastric cancer, providing a new direction for future research in this field.
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Affiliation(s)
- Hui Huang
- Chengdu Medical College, Chengdu, Sichuan, China
| | - Wei Zhong
- Chengdu Medical College, Chengdu, Sichuan, China
| | | | - Ying Yang
- Chengdu Medical College, Chengdu, Sichuan, China
| | - Tianmu Wu
- Chengdu Medical College, Chengdu, Sichuan, China
| | - Runyang Chen
- Chengdu Medical College, Chengdu, Sichuan, China
| | - Yanling Liu
- Chengdu Medical College, Chengdu, Sichuan, China
| | - Feng He
- Chengdu Medical College, Chengdu, Sichuan, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Jun Li
- Chengdu Medical College, Chengdu, Sichuan, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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26
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Xi J, Li Y, Zhang H, Bai Z. Dynamic variations of the gastric microbiota: Key therapeutic points in the reversal of Correa's cascade. Int J Cancer 2023; 152:1069-1084. [PMID: 36029278 DOI: 10.1002/ijc.34264] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 08/10/2022] [Accepted: 08/15/2022] [Indexed: 01/21/2023]
Abstract
Correa's cascade is a dynamic process in the development of intestinal-type gastric cancer (GC), and its pathological features, gastric microbiota and interactions between microorganisms and their hosts vary at different developmental stages. The characteristics of cells, tissues and gastric microbiota before or after key therapeutic points are critical for monitoring malignant transformation and early tumour reversal. This review summarises the pathological features of gastric mucosa, characteristics of gastric microbiota, specific microbial markers, microbe-microbe interactions and microbe-host interactions at different stages in Correa's cascade. The markers related to each Correa's cascade point were analysed in detail. We attempted to identify key therapeutic points for early cancer reversal and provide a novel approach to reduce the incidence of GC and improve precise treatment.
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Affiliation(s)
- Jiahui Xi
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, Lanzhou, China
| | - Yonghong Li
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumour, Gansu Provincial Hospital, Lanzhou, China
| | - Hui Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhongtian Bai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, Lanzhou, China.,General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
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27
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Yang J, Xu J, Ling Z, Zhou X, Si Y, Liu X, Ji F. Prognostic effects of the gastric mucosal microbiota in gastric cancer. Cancer Sci 2023; 114:1075-1085. [PMID: 36403134 PMCID: PMC9986079 DOI: 10.1111/cas.15661] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/22/2022] [Accepted: 11/13/2022] [Indexed: 11/21/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.
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Affiliation(s)
- Jinpu Yang
- Department of Gastroenterology, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
| | - Jiaren Xu
- Department of Gastrointestinal Surgery, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
| | - Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of MedicineZhejiang UniversityZhejiangHangzhouChina
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
| | - Yongqiang Si
- Department of Gastrointestinal Surgery, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
| | - Xiaosun Liu
- Department of Gastrointestinal Surgery, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina
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28
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Nikitina D, Lehr K, Vilchez-Vargas R, Jonaitis LV, Urba M, Kupcinskas J, Skieceviciene J, Link A. Comparison of genomic and transcriptional microbiome analysis in gastric cancer patients and healthy individuals. World J Gastroenterol 2023; 29:1202-1218. [PMID: 36926663 PMCID: PMC10011954 DOI: 10.3748/wjg.v29.i7.1202] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/19/2022] [Accepted: 12/21/2022] [Indexed: 02/21/2023] Open
Abstract
BACKGROUND Helicobacter pylori and the stomach microbiome play a crucial role in gastric carcinogenesis, and detailed characterization of the microbiome is necessary for a better understanding of the pathophysiology of the disease. There are two common modalities for microbiome analysis: DNA (16S rRNA gene) and RNA (16S rRNA transcript) sequencing. The implications from the use of one or another sequencing approach on the characterization and comparability of the mucosal microbiome in gastric cancer (GC) are poorly studied. AIM To characterize the microbiota of GC using 16S rRNA gene and its transcript and determine difference in the bacterial composition. METHODS In this study, 316 DNA and RNA samples extracted from 105 individual stomach biopsies were included. The study cohort consisted of 29 healthy control individuals and 76 patients with GC. Gastric tissue biopsy samples were collected from damaged mucosa and healthy mucosa at least 5 cm from the tumor tissue. From the controls, healthy stomach mucosa biopsies were collected. From all biopsies RNA and DNA were extracted. RNA was reverse transcribed into cDNA. V1-V2 region of bacterial 16S rRNA gene from all samples were amplified and sequenced on an Illumina MiSeq platform. Bray-Curtis algorithm was used to construct sample-similarity matrices abundances of taxonomic ranks in each sample type. For significant differences between groups permutational multivariate analysis of variance and Mann-Whitney test followed by false-discovery rate test were used. RESULTS Microbial analysis revealed that only a portion of phylotypes (18%-30%) overlapped between microbial profiles obtained from DNA and RNA samples. Detailed analysis revealed differences between GC and controls depending on the chosen modality, identifying 17 genera at the DNA level and 27 genera at the RNA level. Ten of those bacteria were found to be different from the control group at both levels. The key taxa showed congruent results in various tests used; however, differences in 7 bacteria taxa were found uniquely only at the DNA level, and 17 uniquely only at the RNA level. Furthermore, RNA sequencing was more sensitive for detecting differences in bacterial richness, as well as differences in the relative abundance of Reyranella and Sediminibacterium according to the type of GC. In each study group (control, tumor, and tumor adjacent) were found differences between DNA and RNA bacterial profiles. CONCLUSION Comprehensive microbial study provides evidence for the effect of choice of sequencing modality on the microbiota profile, as well as on the identified differences between case and control.
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Affiliation(s)
- Darja Nikitina
- Institute for Digestive Research, 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
| | - Ramiro Vilchez-Vargas
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
| | | | - Mindaugas Urba
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
| | - Juozas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
| | - Jurgita Skieceviciene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
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29
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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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30
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Wroblewski LE, Peek RM. Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development. Curr Top Microbiol Immunol 2023; 444:25-52. [PMID: 38231214 PMCID: PMC10924282 DOI: 10.1007/978-3-031-47331-9_2] [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] [Indexed: 01/18/2024]
Abstract
The human pathogen Helicobacter pylori is the strongest known risk factor for gastric disease and cancer, and gastric cancer remains a leading cause of cancer-related death across the globe. Carcinogenic mechanisms associated with H. pylori are multifactorial and are driven by bacterial virulence constituents, host immune responses, environmental factors such as iron and salt, and the microbiota. Infection with strains that harbor the cytotoxin-associated genes (cag) pathogenicity island, which encodes a type IV secretion system (T4SS) confer increased risk for developing more severe gastric diseases. Other important H. pylori virulence factors that augment disease progression include vacuolating cytotoxin A (VacA), specifically type s1m1 vacA alleles, serine protease HtrA, and the outer-membrane adhesins HopQ, BabA, SabA and OipA. Additional risk factors for gastric cancer include dietary factors such as diets that are high in salt or low in iron, H. pylori-induced perturbations of the gastric microbiome, host genetic polymorphisms, and infection with Epstein-Barr virus. This chapter discusses in detail host factors and how H. pylori virulence factors augment the risk of developing gastric cancer in human patients as well as how the Mongolian gerbil model has been used to define mechanisms of H. pylori-induced inflammation and cancer.
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Affiliation(s)
- Lydia E Wroblewski
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
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31
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Isaeva GS, Isaeva R. Mechanisms of microbial interactions between probiotic microorganisms
and Helicobacter pylori. CLINICAL MICROBIOLOGY AND ANTIMICROBIAL CHEMOTHERAPY 2023; 25:225-238. [DOI: 10.36488/cmac.2023.3.225-238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Infection caused by Helicobacter pylori is currently one of the most common infection in the world, but the clinical picture can vary from asymptomatic manifestations to the development of stomach cancer. In order to eradicate the pathogen various regimens of antibacterial therapy have been proposed, but recent studies indicate a decrease in efficiency of this therapy due to the increasing rate of H. pylori resistance to antibiotics, the appearance of side effects, including the development of dysbiosis. One of the perspective directions of an alternative approach to the treatment of helicobacteriosis is probiotic therapy. The usage of probiotic therapy of H. pylori infection has two main directions. The first one is associated with the usage of probiotics to reduce the frequency of undesirable effects from the gastrointestinal tract during H. pylori antimicrobial therapy and the second one is the potentiation of the eradication effect due to the antagonistic effect on H. pylori. The purpose of this review was to summarize the latest data about the mechanisms of microbial interactions between probiotic microorganisms and H. pylori. The review examines the influence of H. pylori on the gastrointestinal microbiota, interspecific interactions of microorganisms in microbial consortia, mechanisms of antagonistic action of probiotic cultures on H. pylori, as well as the analysis of experience of using probiotics in the treatment of helicobacteriosis. At the same time, there will be many unresolved questions about the choice of the specific composition of the probiotic cocktail, dosage, duration of therapy, mechanisms of antimicrobial action of probiotics, as well as possible negative sides of this therapy, which requires further research.
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Affiliation(s)
- Guzel Sh. Isaeva
- Kazan Research Institute of Epidemiology and Microbiology, Kazan State Medical University (Kazan, Russia)
| | - R.A. Isaeva
- Kazan Research Institute of Epidemiology and Microbiology, Kazan State Medical University (Kazan, Russia)
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32
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Xu Z, Xiao L, Wang S, Cheng Y, Wu J, Meng Y, Bao K, Zhang J, Cheng C. Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid. Front Microbiol 2023; 14:1160821. [PMID: 37206332 PMCID: PMC10188980 DOI: 10.3389/fmicb.2023.1160821] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/17/2023] [Indexed: 05/21/2023] Open
Abstract
Objective Bile reflux plays a key role in the development of gastric intestinal metaplasia (GIM), an independent risk factor of gastric cancer. Here, we aimed to explore the biological mechanism of GIM induced by bile reflux in a rat model. Methods Rats were treated with 2% sodium salicylate and allowed to freely drink 20 mmol/L sodium deoxycholate for 12 weeks, and GIM was confirmed by histopathological analysis. Gastric microbiota was profiled according to the 16S rDNA V3-V4 region, gastric transcriptome was sequenced, and serum bile acids (BAs) were analyzed by targeted metabolomics. Spearman's correlation analysis was used in constructing the network among gastric microbiota, serum BAs, and gene profiles. Real-time polymerase chain reaction (RT-PCR) measured the expression levels of nine genes in the gastric transcriptome. Results In the stomach, deoxycholic acid (DCA) decreased the microbial diversity but promoted the abundances of several bacterial genera, such as Limosilactobacillus, Burkholderia-Caballeronia-Paraburkholderia, and Rikenellaceae RC9 gut group. Gastric transcriptome showed that the genes enriched in gastric acid secretion were significantly downregulated, whereas the genes enriched in fat digestion and absorption were obviously upregulated in GIM rats. The GIM rats had four promoted serum BAs, namely cholic acid (CA), DCA, taurocholic acid, and taurodeoxycholic acid. Further correlation analysis showed that the Rikenellaceae RC9 gut group was significantly positively correlated with DCA and RGD1311575 (capping protein-inhibiting regulator of actin dynamics), and RGD1311575 was positively correlated with Fabp1 (fatty acid-binding protein, liver), a key gene involved in fat digestion and absorption. Finally, the upregulated expression of Dgat1 (diacylglycerol acyltransferase 1) and Fabp1 related to fat digestion and absorption was identified by RT-PCR and IHC. Conclusion DCA-induced GIM enhanced gastric fat digestion and absorption function and impaired gastric acid secretion function. The DCA-Rikenellaceae RC9 gut group-RGD1311575/Fabp1 axis might play a key role in the mechanism of bile reflux-related GIM.
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Affiliation(s)
- Zijing Xu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ling Xiao
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shuaishuai Wang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yuqin Cheng
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jianping Wu
- Laboratory Animal Center, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yufen Meng
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Kaifan Bao
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Junfeng Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- *Correspondence: Junfeng Zhang
| | - Chun Cheng
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Chun Cheng
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Mendes-Rocha M, Pereira-Marques J, Ferreira RM, Figueiredo C. Gastric Cancer: The Microbiome Beyond Helicobacter pylori. Curr Top Microbiol Immunol 2023; 444:157-184. [PMID: 38231218 DOI: 10.1007/978-3-031-47331-9_6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Gastric cancer remains an important global health burden. Helicobacter pylori is the major etiological factor in gastric cancer, infecting the stomach of almost half of the population worldwide. Recent progress in microbiome research offered a new perspective on the complexity of the microbial communities of the stomach. Still, the role of the microbiome of the stomach beyond H. pylori in gastric carcinogenesis is not well understood and requires deeper investigation. The gastric bacterial communities of gastric cancer patients are distinct from those of patients without cancer, but the microbial alterations that occur along the process of gastric carcinogenesis, and the mechanisms through which microorganisms influence cancer progression still need to be clarified. Except for Epstein-Barr virus, the potential significance of the virome and of the mycobiome in gastric cancer have received less attention. This chapter updates the current knowledge regarding the gastric microbiome, including bacteria, viruses, and fungi, within the context of H. pylori-mediated carcinogenesis. It also reviews the possible roles of the local gastric microbiota, as well as the microbial communities of the oral and gut ecosystems, as biomarkers for gastric cancer detection. Finally, it discusses future perspectives and acknowledges limitations in the area of microbiome research in the gastric cancer setting, to which further research efforts should be directed. These will be fundamental not only to increase our current understanding of host-microbial interactions but also to facilitate translation of the findings into innovative preventive, diagnostic, and therapeutic strategies to decrease the global burden of gastric cancer.
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Affiliation(s)
- Melissa Mendes-Rocha
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal
- Ipatimup-Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
| | - Joana Pereira-Marques
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal
- Ipatimup-Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
| | - Rui M Ferreira
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal
- Ipatimup-Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
| | - Ceu Figueiredo
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
- Ipatimup-Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
- Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
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Zhang L, Zhao M, Fu X. Gastric microbiota dysbiosis and Helicobacter pylori infection. Front Microbiol 2023; 14:1153269. [PMID: 37065152 PMCID: PMC10098173 DOI: 10.3389/fmicb.2023.1153269] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 03/14/2023] [Indexed: 04/18/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is one of the most common causes of gastric disease. The persistent increase in antibiotic resistance worldwide has made H. pylori eradication challenging for clinicians. The stomach is unsterile and characterized by a unique niche. Communication among microorganisms in the stomach results in diverse microbial fitness, population dynamics, and functional capacities, which may be positive, negative, or neutral. Here, we review gastric microecology, its imbalance, and gastric diseases. Moreover, we summarize the relationship between H. pylori and gastric microecology, including non-H. pylori bacteria, fungi, and viruses and the possibility of facilitating H. pylori eradication by gastric microecology modulation, including probiotics, prebiotics, postbiotics, synbiotics, and microbiota transplantation.
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Affiliation(s)
- Ling Zhang
- Department of Gastroenterology, Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Ming Zhao
- Department of Gastroenterology, Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Xiangsheng Fu
- Department of Gastroenterology, Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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35
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Wang M, Lou E, Xue Z. The role of bile acid in intestinal metaplasia. Front Physiol 2023; 14:1115250. [PMID: 36891144 PMCID: PMC9986488 DOI: 10.3389/fphys.2023.1115250] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 02/10/2023] [Indexed: 02/22/2023] Open
Abstract
A precancerous lesion of gastric cancer (GC), intestinal metaplasia (IM) is a pathological transformation of non-intestinal epithelium into an intestinal-like mucosa. It greatly raises the risk of developing the intestinal type of GC, which is frequently observed in the stomach and esophagus. It is understood that esophageal adenocarcinoma's precursor lesion, chronic gastroesophageal reflux disease (GERD), is what causes Barrett's esophagus (BE), an acquired condition. Recently, Bile acids (BAs), which are one of the compositions of gastric and duodenal contents, have been confirmed that it led to the occurrence and development of BE and gastric intestinal metaplasia (GIM). The objective of the current review is to discuss the mechanism of IM induced by bile acids. This review serves as a foundation for further research aimed at improving the way BE and GIM are currently managed.
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Affiliation(s)
- Menglei Wang
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
| | - Enzhe Lou
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
| | - Zengfu Xue
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
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Ramai D, Salati M, Pomati G, Amoroso C, Facciorusso A, Botticelli A, Ghidini M. Antibiotics, the microbiome and gastrointestinal cancers: A causal interference? Curr Opin Pharmacol 2022; 67:102315. [PMID: 36351361 DOI: 10.1016/j.coph.2022.102315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/03/2022] [Accepted: 10/08/2022] [Indexed: 11/07/2022]
Abstract
Our understanding of the gut microbiota has significantly evolved over the last two decades. Advances in the analysis of the gut microbiome continues to reveal complex microbial communities and discoveries about their role in health and diseases, including cancer development, are continuously growing. In addition, research has demonstrated that the use of antibiotics can modulate the gut microbiota composition negatively and influence cancer treatment outcomes, suggesting that antibiotics should be avoided if possible. In this article, we review the role of the gut microbiota in the formation of GI cancers. We show that specific bacterial populations can positively or negatively affect cancer formation with specific attention given to gastric and colorectal cancer. We also review the role of microbial-targeted therapies on cancer treatment outcomes.
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Affiliation(s)
- Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah Health, Salt Lake City, UT, USA
| | - Massimiliano Salati
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy
| | - Giulia Pomati
- Department of Molecular Medicine, Sapienza University of Rome, Italy
| | - Chiara Amoroso
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Andrea Botticelli
- Department of Radiological, Oncological, Pathological Department, La Sapienza, University of Rome, Policlinico Umberto I, Rome, Italy
| | - Michele Ghidini
- Division of Medical Oncology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
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Zi M, Zhang Y, Hu C, Zhang S, Chen J, Yuan L, Cheng X. A literature review on the potential clinical implications of streptococci in gastric cancer. Front Microbiol 2022; 13:1010465. [PMID: 36386672 PMCID: PMC9643750 DOI: 10.3389/fmicb.2022.1010465] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 10/03/2022] [Indexed: 10/29/2023] Open
Abstract
Streptococcus is widely found in nature and the human body, and most species are not pathogenic. In recent years, studies have found that Streptococcus is associated with gastric cancer. Streptococcus was found to be enriched in the oral cavity, stomach and intestine of gastric cancer patients and found to be increased in gastric cancer tissues, suggesting that Streptococcus may be the pathogenic bacteria underlying gastric cancer. This review discusses the discovery of Streptococcus, the relationship between Streptococcus and gastric cancer, and the possible carcinogenic mechanism of Streptococcus and summarizes the progress of the research on the role of Streptococcus in gastric cancer to provide new ideas for the early detection, diagnosis and treatment of gastric cancer.
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Affiliation(s)
- Mengli Zi
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Yanqiang Zhang
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Can Hu
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Shengjie Zhang
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jinxia Chen
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Li Yuan
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xiangdong Cheng
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
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Comparison of the gastric microbiome in Billroth I and Roux-en-Y reconstructions after distal gastrectomy. Sci Rep 2022; 12:10594. [PMID: 35732881 PMCID: PMC9217802 DOI: 10.1038/s41598-022-14886-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 06/14/2022] [Indexed: 11/25/2022] Open
Abstract
The changes in gastric microbiota following reconstruction after gastrectomy have not been reported. This study aimed to compare the gastric microbiota following Billroth I and Roux-en-Y reconstructions after distal gastrectomy. We enrolled 71 gastrectomized patients with gastric cancer; 31 and 40 underwent Billroth I and Roux-en-Y reconstructions, respectively. During upper gastrointestinal endoscopy, gastric fluid was collected immediately before and 6 months after distal gastrectomy. Deoxyribonucleic acid isolated from each sample was evaluated using 16S ribosomal ribonucleic acid metagenomic analysis. Analysis revealed that the gastric microbiota’s species richness (expressed as the alpha diversity) was significantly lower after than before distal gastrectomy (operational taxonomic units, p = 0.001; Shannon index, p = 0.03). The interindividual diversity (beta diversity) was significantly different before and after distal gastrectomy (unweighted UniFrac distances, p = 0.04; weighted UniFrac distances, p = 0.001; Bray–Curtis, p = 0.001). Alpha and beta diversity were not significantly different between Billroth I and Roux-en-Y reconstructions (observed operational taxonomic units, p = 0.58; Shannon index, p = 0.95; unweighted UniFrac distances, p = 0.65; weighted UniFrac distances, p = 0.67; Bray–Curtis, p = 0.63). Our study demonstrated significant differences in gastric microbiota diversity, composition, and community before and after distal gastrectomy but no difference between Billroth I and Roux-en-Y reconstruction after distal gastrectomy.
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Inflammation and Gastric Cancer. Diseases 2022; 10:diseases10030035. [PMID: 35892729 PMCID: PMC9326573 DOI: 10.3390/diseases10030035] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/16/2022] [Accepted: 06/19/2022] [Indexed: 11/17/2022] Open
Abstract
Gastric cancer remains a major killer globally, although its incidence has declined over the past century. It is the fifth most common cancer and the third most common reason for cancer-related deaths worldwide. Gastric cancer is the outcome of a complex interaction between environmental, host genetic, and microbial factors. There is significant evidence supporting the association between chronic inflammation and the onset of cancer. This association is particularly robust for gastrointestinal cancers in which microbial pathogens are responsible for the chronic inflammation that can be a triggering factor for the onset of those cancers. Helicobacter pylori is the most prominent example since it is the most widespread infection, affecting nearly half of the world’s population. It is well-known to be responsible for inducing chronic gastric inflammation progressing to atrophy, metaplasia, dysplasia, and eventually, gastric cancer. This review provides an overview of the association of the factors playing a role in chronic inflammation; the bacterial characteristics which are responsible for the colonization, persistence in the stomach, and triggering of inflammation; the microbiome involved in the chronic inflammation process; and the host factors that have a role in determining whether gastritis progresses to gastric cancer. Understanding these interconnections may improve our ability to prevent gastric cancer development and enhance our understanding of existing cases.
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40
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Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis. Oncogene 2022; 41:3599-3610. [PMID: 35680985 PMCID: PMC9270228 DOI: 10.1038/s41388-022-02377-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/27/2022] [Accepted: 06/01/2022] [Indexed: 12/17/2022]
Abstract
The consistency of the associations between gastric mucosal microbiome and gastric cancer across studies remained unexamined. We aimed to identify universal microbial signatures in gastric carcinogenesis through a meta-analysis of gastric microbiome from multiple studies. Compositional and ecological profiles of gastric microbes across stages of gastric carcinogenesis were significantly altered. Meta-analysis revealed that opportunistic pathobionts Fusobacterium, Parvimonas, Veillonella, Prevotella and Peptostreptococcus were enriched in GC, while commensals Bifidobacterium, Bacillus and Blautia were depleted in comparison to SG. The co-occurring correlation strengths of GC-enriched bacteria were increased along disease progression while those of GC-depleted bacteria were decreased. Eight bacterial taxa, including Veillonella, Dialister, Granulicatella, Herbaspirillum, Comamonas, Chryseobacterium, Shewanella and Helicobacter, were newly identified by this study as universal biomarkers for robustly discriminating GC from SG, with an area under the curve (AUC) of 0.85. Moreover, H. pylori-positive samples exhibited reduced microbial diversity, altered microbiota community and weaker interactions among gastric microbes. Our meta-analysis demonstrated comprehensive and generalizable gastric mucosa microbial features associated with histological stages of gastric carcinogenesis, including GC associated bacteria, diagnostic biomarkers, bacterial network alteration and H. pylori influence.
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41
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Chen Y, Zhiliang L, Jiaqu C, Xiaoqiong L, Shaoyi Z, Chunlian M, Yinmei Y, Bo Y, Di Z, Hongliang T, Ning L, Qiyi C, Huanlong Q. Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook. Front Med (Lausanne) 2022; 9:830004. [PMID: 35665355 PMCID: PMC9158325 DOI: 10.3389/fmed.2022.830004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 04/11/2022] [Indexed: 11/13/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.
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Affiliation(s)
- Ye Chen
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Lin Zhiliang
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Cui Jiaqu
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Lv Xiaoqiong
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Zhang Shaoyi
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Ma Chunlian
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Yan Yinmei
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Yang Bo
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Zhao Di
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Tian Hongliang
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Li Ning
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Chen Qiyi
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
| | - Qin Huanlong
- Department of Colorectal Disease Specialty, Clinical Research Center for Digestive Diseases, The Tenth People's Hospital, Tongji University, Shanghai, China
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Yang J, Liu X, Cheng Y, Zhang J, Ji F, Ling Z. Roles of Plasmacytoid Dendritic Cells in Gastric Cancer. Front Oncol 2022; 12:818314. [PMID: 35311157 PMCID: PMC8927765 DOI: 10.3389/fonc.2022.818314] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/15/2022] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies.
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Affiliation(s)
- Jinpu Yang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xia Liu
- Department of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yiwen Cheng
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jingchen Zhang
- Department of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
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Gastric Non-Helicobacter pylori Urease-Positive Staphylococcus epidermidis and Streptococcus salivarius Isolated from Humans Have Contrasting Effects on H. pylori-Associated Gastric Pathology and Host Immune Responses in a Murine Model of Gastric Cancer. mSphere 2022; 7:e0077221. [PMID: 35138124 PMCID: PMC8826947 DOI: 10.1128/msphere.00772-21] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
In populations with similar prevalence of Helicobacter pylori infection, cancer risk can vary dramatically. Changes in composition or structure of bacterial communities in the stomach, either at the time of exposure or over the course of H. pylori infection, may contribute to gastric pathology. In this study, a population of 37 patients from the low-gastric-cancer-risk (LGCR) region of Tumaco, Colombia, and the high-gastric-cancer-risk (HGCR) region of Túquerres, Colombia, were recruited for gastric endoscopy. Antral biopsy specimens were processed for histology and bacterial isolation. Fifty-nine distinct species among 26 genera were isolated by aerobic, anaerobic, and microaerobic culture and confirmed by 16S rRNA analysis. Urease-positive Staphylococcus epidermidis and Streptococcus salivarius were frequently isolated from gastric biopsy specimens. We asked whether coinfection of H. pylori with urease-positive S. salivarius and/or S. epidermidis had a demonstrable effect on H. pylori-induced gastritis in the germfree (GF) INS-GAS mouse model. Coinfections with S. salivarius and/or S. epidermidis did not affect gastric H. pylori colonization. At 5 months postinfection, GF INS-GAS mice coinfected with H. pylori and S. salivarius had statistically higher pathological scores in the stomachs than mice infected with H. pylori only or H. pylori with S. epidermidis (P < 0.05). S. epidermidis coinfection with H. pylori did not significantly change stomach pathology, but levels of the proinflammatory cytokine genes Il-1β, Il-17A , and Il-22 were significantly lower than in H. pylori-monoinfected mice. This study demonstrates that non-H. pylori urease-positive bacteria may play a role in the severity of H. pylori-induced gastric cancer in humans. IMPORTANCE Chronic infection with H. pylori is the main cause of gastric cancer, which is a global health problem. In two Colombian populations with high levels of H. pylori prevalence, the regional gastric cancer rates are considerably different. Host genetic background, H. pylori biotype, environmental toxins, and dietary choices are among the known risk factors for stomach cancer. The potential role of non-H. pylori gastric microbiota in gastric carcinogenesis is being increasingly recognized. In this study, we isolated 59 bacterial species from 37 stomach biopsy samples of Colombian patients from both low-gastric-cancer-risk and high-gastric-cancer-risk regions. Urease-positive S. epidermidis and S. salivarius commonly cultured from the stomachs, along with H. pylori, were inoculated into germfree INS-GAS mice. S. salivarius coinfection with H. pylori induced significantly higher gastric pathology than in H. pylori-monoinfected mice, whereas S. epidermidis coinfection caused significantly lower H. pylori-induced proinflammatory cytokine responses than in H. pylori-monoinfected mice. This study reinforces the argument that the non-H. pylori stomach microflora play a role in the severity of H. pylori-induced gastric cancer.
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Lu Y, Liu H, Yang K, Mao Y, Meng L, Yang L, Ouyang G, Liu W. A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine. J Zhejiang Univ Sci B 2022; 23:1-18. [PMID: 35029085 DOI: 10.1631/jzus.b2100182] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.
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Affiliation(s)
- Yuting Lu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China
| | - Huayi Liu
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China.
| | - Kuo Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China
| | - Yijia Mao
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China
| | - Lingkai Meng
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China
| | - Liu Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China
| | - Guangze Ouyang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China
| | - Wenjie Liu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China
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Isaeva G, Isaeva R. Probiotics in the treatment of Helicobacter pylori infection: reality and perspective. Minerva Gastroenterol (Torino) 2022; 68:277-288. [PMID: 35001603 DOI: 10.23736/s2724-5985.21.02926-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Helicobacter pylori (H. pylori) infection is one of the most common in the world today, associated with the development of acute or chronic inflammatory diseases of the gastroduodenal tract. In order to eradicate the pathogen, various antibacterial therapy regimens have been proposed, based on the use of several chemotherapeutic drugs and a proton pump inhibitor (PPI). However, recent studies indicate a decrease in antibiotic effectiveness due to both the growth rate of H. pylori resistance and side effects, often due to the development of dysbiosis. One of the promising areas of investigation is the treatment with probiotic therapy of helicobacteriosis. The use of probiotics, in the context of H. pylori infection, has two main reasons. The first is related to the use of certain probiotics to reduce the frequency of undesirable gastrointestinal consequences during H. pylori eradication therapy. The second is associated with the antagonistic effect of individual probiotics on H. pylori and the potentiation of the eradication effect. The purpose of this review was to summarize the latest data on the use of probiotics to enhance H. pylori eradication and to restore the gastrointestinal microbiota. Many unresolved questions, about the choice of the specific composition of the probiotic cocktail, dosage, duration of therapy, mechanisms of the antimicrobial action of probiotics, as well as possible negative consequences of such therapy, remain.
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Affiliation(s)
- Guzel Isaeva
- Kazan Research Institute of Epidemiology and Microbiology, Kazan, Russian Federation - .,Microbiology Department, Kazan State Medical University, Kazan, Russian Federation -
| | - Regina Isaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
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Jin D, Huang K, Xu M, Hua H, Ye F, Yan J, Zhang G, Wang Y. Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota. Gut Microbes 2022; 14:2120744. [PMID: 36067404 PMCID: PMC9467587 DOI: 10.1080/19490976.2022.2120744] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 08/22/2022] [Accepted: 08/31/2022] [Indexed: 02/04/2023] Open
Abstract
Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.
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Affiliation(s)
- Duochen Jin
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
- First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Keting Huang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
- First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Miao Xu
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
- First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Hongjin Hua
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Feng Ye
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
| | - Jin Yan
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
| | - Guoxin Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
- First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yun Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, NanjingChina
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Miladinović-Tasić N, Nikolić K, Arizanović K. Oral cavity protozoa relevant in the practice of dentistry. ACTA STOMATOLOGICA NAISSI 2022. [DOI: 10.5937/asn2285352m] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Introduction: Oral cavity is the colonization site of most diverse microorganisms. The homeostasis of oral microbioma is affected by numerous factors. Periodontal diseases occur as a consequence of disturbed oral microbioma homeostasis, when an inflammatory reaction occurs in the periodontal tissue. The impact of parasites on periodontal pathophysiology has not been sufficiently studied, and present and future research should hopefully answer quite a few questions concerning the issue. Aim of the paper: In the light of the present knowledge of the pathogenesis, diagnosis and epidemiology of oral cavity infections caused by Entamoeba gingivalis and Trichomonas tenax, the aim of the paper was review of literature which could to point to the importance of protozoa in the practice of dentistry and to possible oral cavity manifestations of parasitic infections relevant for public health. Conclusion: Dentists have an essential role in the diagnosis of oral diseases caused by oral cavity protozoa, and protozoa relevant for public health that produce systemic infections, the pathological changes of which may manifest in the oral cavity. Their identification represents a challenge and requires multidisciplinary approach for a timely diagnosis and adequate management.
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Retnakumar R, Nath AN, Nair GB, Chattopadhyay S. Gastrointestinal microbiome in the context of Helicobacter pylori infection in stomach and gastroduodenal diseases. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 192:53-95. [DOI: 10.1016/bs.pmbts.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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49
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Yang H, Wei B, Hu B. Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer. Inflamm Res 2021; 70:1015-1026. [PMID: 34549319 DOI: 10.1007/s00011-021-01501-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/13/2021] [Accepted: 09/09/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) infects approximately half of the world's population, as one of the most common chronic infections. H. pylori infection has been widely recognized as a major risk factor for gastric cancer (GC). METHODS Eradication treatment is considered to abolish the inflammatory response and prevent progression to GC. However, only 1-3% of H. pylori-infected patients develop GC, whereas GC can occur even after eradicating H. pylori. In addition, the incidence of GC following H. pylori infection is significantly higher compared to the gross incidence induced by all causes, although eradicating H. pylori reduces the risk of developing GC. RESULTS Therefore, it is reasonable to hypothesize that H. pylori infection results in changes that persist even after its eradication. Several of these changes may not be reversible within a short time, including the status of inflammation, the dysfunction of immunity and apoptosis, mitochondrial changes, aging and gastric dysbacteriosis. CONCLUSION The present review article aimed to discuss these potential long-lasting changes induced by H. pylori infection that may follow the eradication of H. pylori and contribute to the development of GC.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China
| | - Bin Wei
- Department of Gastroenterology, The First Hospital of Xi'an City, Xi'an, 710002, Shanxi, People's Republic of China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
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50
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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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