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Ghuriani V, Wassan JT, Tripathi P, Chauhan A. XGB-BIF: An XGBoost-Driven Biomarker Identification Framework for Detecting Cancer Using Human Genomic Data. Int J Mol Sci 2025; 26:5590. [PMID: 40565055 DOI: 10.3390/ijms26125590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2025] [Revised: 06/03/2025] [Accepted: 06/05/2025] [Indexed: 06/28/2025] Open
Abstract
The human genome has a profound impact on human health and disease detection. Carcinoma (cancer) is one of the prominent diseases that majorly affect human health and requires the development of different treatment strategies and targeted therapies based on effective disease detection. Therefore, our research aims to identify biomarkers associated with distinct cancer types (gastric, lung, and breast) using machine learning. In the current study, we have analyzed the human genomic data of gastric cancer, breast cancer, and lung cancer patients using XGB-BIF (i.e., XGBoost-Driven Biomarker Identification Framework for detecting cancer). The proposed framework utilizes feature selection via XGBoost (eXtreme Gradient Boosting), which captures feature interactions efficiently and takes care of the non-linear effects in the genomic data. The research progressed by training XGBoost on the full dataset, ranking the features based on the Gain measure (importance), followed by the classification phase, which employed support vector machines (SVM), logistic regression (LR), and random forest (RF) models for classifying cancer-diseased and non-diseased states. To ensure interpretability and transparency, we also applied SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME), enabling the identification of high-impact biomarkers contributing to risk stratification. Biomarker significance is discussed primarily via pathway enrichment and by studying survival analysis (Kaplan-Meier curves, Cox regression) for identified biomarkers to strengthen translational value. Our models achieved high predictive performance, with an accuracy of more than 90%, to classify and link genomic data into diseased (cancer) and non-diseased states. Furthermore, we evaluated the models using Cohen's Kappa statistic, which confirmed strong agreement between predicted and actual risk categories, with Kappa scores ranging from 0.80 to 0.99. Our proposed framework also achieved strong predictions on the METABRIC dataset during external validation, attaining an AUC-ROC of 93%, accuracy of 0.79%, and Kappa of 74%. Through extensive experimentation, XGB-BIF identified the top biomarker genes for different cancer datasets (gastric, lung, and breast). CBX2, CLDN1, SDC2, PGF, FOXS1, ADAMTS18, POLR1B, and PYCR3 were identified as important biomarkers to identify diseased and non-diseased states of gastric cancer; CAVIN2, ADAMTS5, SCARA5, CD300LG, and GIPC2 were identified as important biomarkers for breast cancer; and CLDN18, MYBL2, ASPA, AQP4, FOLR1, and SLC39A8 were identified as important biomarkers for lung cancer. XGB-BIF could be utilized for identifying biomarkers of different cancer types using genetic data, which can further help clinicians in developing targeted therapies for cancer patients.
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Affiliation(s)
- Veena Ghuriani
- Maitreyi College, University of Delhi, New Delhi 110021, India
| | | | - Priyal Tripathi
- Maitreyi College, University of Delhi, New Delhi 110021, India
| | - Anshika Chauhan
- Maitreyi College, University of Delhi, New Delhi 110021, India
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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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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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Zhang X, Li Q, Xia S, He Y, Liu Y, Yang J, Xiao X. Proton Pump Inhibitors and Oral-Gut Microbiota: From Mechanism to Clinical Significance. Biomedicines 2024; 12:2271. [PMID: 39457584 PMCID: PMC11504961 DOI: 10.3390/biomedicines12102271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 09/13/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
Proton pump inhibitors (PPIs) are some of the most commonly prescribed drugs worldwide, but there are increasing concerns about digestive complications linked to PPIs. Next-generation sequencing studies have suggested that PPIs can significantly affect the composition of the gut microbiota, which in turn may substantially contribute to the development of these complications. Recently, emerging evidence has suggested that the translocation of oral microbes into the gut may be the primary mechanism underlying the alterations in the gut microbiota induced by PPIs in the presence of gastric acid suppression and impaired oral-gut barrier function. Moreover, the significance of oral-gut microbial translocation in health and disease conditions has gained increasing recognition. Consequently, it is imperative to enhance our understanding of the functions of the oral-gut microbiota axis in digestive disorders associated with PPI therapies. This review aims to summarize current research findings and further elucidate the contribution of the oral-gut microbiota to the pathogenesis of PPI-related digestive diseases. We aim to provide a theoretical foundation for future therapeutic and preventive strategies targeting PPI-related digestive complications through modulation of the oral-gut microbiota.
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Affiliation(s)
- Xian Zhang
- Department of Pathology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Qing Li
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
| | - Siyuan Xia
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
| | - Yan He
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
| | - Yuqiang Liu
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
| | - Jinlin Yang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
| | - Xue Xiao
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; (Q.L.); (S.X.); (Y.L.); (J.Y.)
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Parveen S, Alqahtani AS, Aljabri MY, Dawood T, Khan SS, Gupta B, Vempalli S, Hassan AAHAA, Elamin NMH. Exploring the Interplay: Oral–Gut Microbiome Connection and the Impact of Diet and Nutrition. EUROPEAN JOURNAL OF GENERAL DENTISTRY 2024; 13:165-176. [DOI: 10.1055/s-0044-1786154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
AbstractThe intricate interplay between the oral and intestinal microbiota holds increasing fascination within the context of health and nutrition. Serving as the gateway to the gastrointestinal tract, the oral microbiota hosts a diverse array of microbial species that significantly influence well-being or contribute to various diseases. Dysbiosis in the oral microbiota has been linked to conditions such as dental caries, periodontal diseases, and systemic disorders, including diabetes, cardiovascular disease, obesity, rheumatoid arthritis, Alzheimer's disease, and colorectal cancer. This review aims to comprehend the nuanced relationship between oral and intestinal microbiotas, exploring the pivotal role of diet in developing strategies for wellness promotion and disease prevention. Drawing insights from a myriad of studies encompassing both animals and humans, we examine the implications of microbial dysbiosis and its impact on health. A bibliographic search of 78 scientific articles was conducted across PubMed Central, Web of Science, Scopus, Google Scholar, and the Saudi digital library from January 2000 to August 2023. Following a rigorous screening process, the full texts of selected articles were critically reviewed to extract relevant information. Articles not meeting the inclusion criteria—specifically focused on oral–intestinal microbiota interaction and diet and nutrition—were meticulously excluded. Diet emerges as a key player in influencing both oral and intestinal microbiotas. Various dietary components, such as fiber, prebiotics, probiotics, and bioactive compounds, have demonstrated significant effects on the diversity and function of microorganisms in these ecosystems. Conversely, diets high in processed foods, added sugars, and saturated fats correlate with dysbiosis and an elevated risk of oral and gastrointestinal diseases. Understanding the intricacies of this interaction is paramount for the development of innovative approaches fostering a balanced oral–gut microbiota axis and improving overall human health. The implications extend to preventive and therapeutic interventions, emphasizing the practical importance of unraveling these complexities for public health and clinical practice. This comprehensive review delves into the intricate relationship between gut and oral microbiota, shedding light on their roles in various diseases, particularly focusing on oral diseases. Key findings are summarized, and implications for future research and clinical practice are discussed. In conclusion, the review underscores the urgent need for special attention to key microbiota in developing targeted interventions for promoting oral and gut health.
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Affiliation(s)
- Sameena Parveen
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Ahmed Shaher Alqahtani
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Mohammed Y. Aljabri
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Tazeen Dawood
- Department of Preventive Dental Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Samar Saeed Khan
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Bharti Gupta
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Swetha Vempalli
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
| | | | - Nahid Mahmoud Hassan Elamin
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia
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Lee H, Yang X, Jin PR, Won KJ, Kim CH, Jeong H. The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity. Drug Metab Dispos 2024; 52:754-764. [PMID: 38302428 PMCID: PMC11257691 DOI: 10.1124/dmd.123.001541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/11/2024] [Accepted: 01/29/2024] [Indexed: 02/03/2024] Open
Abstract
The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is a major organ exposed to gut microbial metabolites, and it serves as the nexus for maintaining healthy interactions between the gut microbiota and the host. At the same time, the liver is the primary target of potentially harmful gut microbial metabolites. In this review, we provide an up-to-date list of gut microbial metabolites that have been identified to either increase or decrease host susceptibility to acetaminophen (APAP)-induced liver injury. The signaling pathways and molecular factors involved in the progression of APAP-induced hepatotoxicity are well-established, and we propose that the mouse model of APAP-induced hepatotoxicity serves as a model system for uncovering gut microbial metabolites with previously unknown functions. Furthermore, we envision that gut microbial metabolites identified to alter APAP-induced hepatotoxicity likely have broader implications in other liver diseases. SIGNIFICANCE STATEMENT: This review provides an overview of the role of the gut microbiota in modulating the host susceptibility to acetaminophen (APAP)-induced liver injury. It focuses on the roles of gut bacterial small molecule metabolites as mediators of the interaction between the gut microbiota and the liver. It also illustrates the utility of APAP-induced liver injury as a model to identify gut microbial metabolites with biological function.
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Affiliation(s)
- Hyunwoo Lee
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
| | - Xiaotong Yang
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
| | - Pei-Ru Jin
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
| | - Kyoung-Jae Won
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
| | - Chang H Kim
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
| | - Hyunyoung Jeong
- Department of Industrial and Molecular Pharmaceutics (H.L., X.Y., P.-R.J., K.-J.W., H.J.), Department of Pharmacy Practice (H.J.), and College of Pharmacy, and Department of Comparative Pathobiology, College of Veterinary Medicine (H.L.), Purdue University, West Lafayette, Indiana and Department of Pathology and Mary H. Weiser Food Allergy Center and Rogel Center for Cancer Research, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.)
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Huang X, Zhang DY, Li D, Lv Y, Chen S, Bai F. Human gastric microbiota analysis of refractory H. pylori infection. Sci Rep 2024; 14:15619. [PMID: 38972876 PMCID: PMC11228035 DOI: 10.1038/s41598-024-66339-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 07/01/2024] [Indexed: 07/09/2024] Open
Abstract
H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection.
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Affiliation(s)
- Xianfeng Huang
- Graduate School, Hainan Medical University, Haikou, 571199, China
| | - Da-Ya Zhang
- Graduate School, Hainan Medical University, Haikou, 571199, China
| | - Da Li
- Graduate School, Hainan Medical University, Haikou, 571199, China
| | - Yanting Lv
- Graduate School, Hainan Medical University, Haikou, 571199, China
| | - Shiju Chen
- Graduate School, Hainan Medical University, Haikou, 571199, China
| | - Feihu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, #368, Longhua District, Haikou, 570216, Hainan Province, China.
- The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, 570216, China.
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Peng C, Xu X, Ouyang Y, Li Y, Lu N, Zhu Y, He C. Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer. Helicobacter 2024; 29:e13117. [PMID: 39086007 DOI: 10.1111/hel.13117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/26/2024] [Accepted: 07/17/2024] [Indexed: 08/02/2024]
Abstract
BACKGROUND Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.
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Affiliation(s)
- Chao Peng
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yaobin Ouyang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yu Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nonghua Lu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Cong He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Huang Y, Kang Z, He Y, Qiu Y, Song Y, Liu W. Association between gut microbiota and common overlapping gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study. Front Microbiol 2024; 15:1343564. [PMID: 38855762 PMCID: PMC11157101 DOI: 10.3389/fmicb.2024.1343564] [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: 11/23/2023] [Accepted: 04/29/2024] [Indexed: 06/11/2024] Open
Abstract
Background The main functional gastrointestinal disorders (FGIDs) include functional dyspepsia (FD) and irritable bowel syndrome (IBS), which often present overlapping symptoms with gastroesophageal reflux disease (GERD), posing a challenge for clinical diagnosis and treatment. The gut microbiota is closely associated with FGIDs and GERD, although the causal relationship has not been fully elucidated. Therefore, we aimed to investigate the potential causal relationship using bidirectional two-sample Mendelian randomization (MR) analysis. Materials and methods The genetic data of the 211 gut microbiota were obtained from the MiBioGen consortium (N = 14,306, from phylum to genus level) and species level of gut microbiota were acquired from the Dutch Microbiome Project (N = 7,738). For FD and IBS, we utilized the FinnGen consortium, whereas, for GERD data analysis, we obtained the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was used as the primary method to calculate causal effect values. Sensitivity analyses were also performed to confirm the robustness of the primary findings of the MR analyses. Moreover, a reverse MR analysis was conducted to assess the likelihood of reverse causality. Results Combining the results of the preliminary and sensitivity analyses, we identified that 8 gut microbial taxa were associated with FD. Genus Lachnospiraceae NK4A136 group (p = 3.63 × 10-3) and genus Terrisporobacter (p = 1.13 × 10-3) were strongly associated with FD. At the same time, we found that 8 gut microbial taxa were associated with IBS. Family Prevotellaceae (p = 2.44 × 10-3) and species Clostridium leptum (p = 7.68 × 10-3) display a robust correlation with IBS. In addition, 5 gut microbial taxa were associated with GERD using the IVW approach. In the reverse MR analysis, 2 gut microbial taxa were found to be associated with FD, 5 gut microbial taxa were found to be associated with IBS, and 21 gut microbial taxa were found to be associated with GERD. Conclusion The study reveals the potential causal effects of specific microbial taxa on FD, IBS, and GERD and may offer novel insights into the diagnosis and treatment of these conditions.
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Affiliation(s)
- Yuhan Huang
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhen Kang
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yuhan He
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yi Qiu
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yuhui Song
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Weiai Liu
- The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- The Second Clinical College of Hunan University of Chinese Medicine, Changsha, Hunan, China
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Wang Y, Jia Y, Liu X, Yang K, Lin Y, Shao Q, Ling J. Effect of Chaihu-Shugan-San on functional dyspepsia and gut microbiota: A randomized, double-blind, placebo-controlled trial. JOURNAL OF ETHNOPHARMACOLOGY 2024; 322:117659. [PMID: 38151181 DOI: 10.1016/j.jep.2023.117659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 11/20/2023] [Accepted: 12/23/2023] [Indexed: 12/29/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chaihu-Shugan-San (CSS) is a classic traditional Chinese medicine (TCM) formula from the Ming Dynasty "Jingyue's Complete Works". In China, it is prevalent for the treatment of a wide range of ailments, with a particular emphasis on functional gastrointestinal disorders (FGIDs). Clinical evidence suggests that CSS has been found to be a highly effective therapeutic approach for the treatment of Functional Dyspepsia (FD), however, there is a limited amount of high-quality clinical evidence, particularly randomized, double-blind, placebo-controlled trials to support this claim. AIM OF THE STUDY To evaluate the therapeutic efficacy of Chaihu-Shugan-San (CSS) for treating functional dyspepsia (FD) by comparing it to placebos, as well as to investigate the impact of CSS on the gut microbiota in individuals diagnosed with FD. MATERIALS AND METHODS This was a randomized double-blind, placebo-controlled clinical trial implemented at Shuguang Hospital in Shanghai. Between May 2021 and December 2022, 94 participants satisfying the Rome IV diagnostic criteria for FD were enrolled. They were assigned randomly to either the CSS group or the placebo group, with an equal allocation ratio of 1:1. Patients in both groups received the intervention for four weeks. The primary outcome was the dyspepsia symptom scores evaluated by using single dyspepsia symptom scale (SDS) after four weeks of treatment. The secondary outcomes were the solid gastric empties rate measured by a barium strip method, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Functional dyspepsia Quality of life scale (FDDQL). In addition, after unblinding, 30 patients in the CSS group were randomly selected and divided into before and after treatment of the FD groups (FD1, FD2), and 30 healthy participants were selected as healthy control group (HC), and the gut microbiota was analyzed by 16S rRNA sequencing. RESULTS After four weeks of treatment, the SDS score exhibited a significant improvement in the CSS group compared to the placebo group (t = 4.882; P ＜0.001). The difference in barium strip gastric emptying rate in the CSS group showed a significant ascent compared to the control group (P < 0.01). The HAMA, HAMD, and FDDQL scores in the CSS group showed a statistically significant increase compared to the control group (all P < 0.01). The results of 16S rRNA sequencing revealed that FD patients had less diverse and abundant microbiota than the healthy people. Additionally, the application of CSS resulted in the modulation of certain bacterial populations, leading to both up-regulation and down-regulation of their quantities. CONCLUSIONS These findings suggested that CSS is more effective compared to a placebo in treating FD, relieves anxiety and depression, increases gastric emptying rate in FD patients, and that CSS also affects the bacterial community structure in FD patients. TRIAL REGISTRATION ChiCTR, ChiCTR2100045793. Registered 25 Mach 2021.
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Affiliation(s)
- Yujiao Wang
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yuebo Jia
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Xuejiao Liu
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Keming Yang
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yunzhi Lin
- Department of TCM, Shanghai Pudong New District Zhoupu Hospital, Shanghai, 201318, China.
| | - Qin Shao
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Jianghong Ling
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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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: 8] [Impact Index Per Article: 4.0] [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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12
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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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13
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Mandarino FV, Sinagra E, Barchi A, Verga MC, Brinch D, Raimondo D, Danese S. Gastroparesis: The Complex Interplay with Microbiota and the Role of Exogenous Infections in the Pathogenesis of the Disease. Microorganisms 2023; 11:1122. [PMID: 37317096 PMCID: PMC10221816 DOI: 10.3390/microorganisms11051122] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 04/23/2023] [Accepted: 04/24/2023] [Indexed: 06/16/2023] Open
Abstract
Gastroparesis (GP) is a disorder of gastric functions that is defined by objective delayed gastric emptying in the absence of mechanical obstruction. This disease is characterized by symptoms such as nausea, post-prandial fullness, and early satiety. GP significantly impacts patients' quality of life and contributes to substantial healthcare expenses for families and society. However, the epidemiological burden of GP is difficult to evaluate, mainly due its significant overlap with functional dyspepsia (FD). GP and FD represent two similar diseases. The pathophysiology of both disorders involves abnormal gastric motility, visceral hypersensitivity, and mucosal inflammation. Moreover, both conditions share similar symptoms, such as epigastric pain, bloating, and early satiety. The latest evidence reveals that dysbiosis is directly or indirectly connected to gut-brain axis alterations, which are the basis of pathogenesis in both FD and GP. Furthermore, the role of microbiota in the development of gastroparesis was demonstrated by some clinical studies, which found that the use of probiotics is correlated with improvements in the gastric emptying time (GET). Infections (with viruses, bacteria, and protozoa) represent a proven etiology for GP but have not been sufficiently considered in current clinical practice. Previous viral infections can be found in about 20% of idiopathic GP cases. Moreover, delayed gastric emptying during systemic protozoal infections represents a huge concern for compromised patients, and few data exist on the topic. This comprehensive narrative review analyzes the relationship between microorganisms and GP. We explore, on the one hand, the correlation between gut microbiota dysbiosis and GP pathogenesis, including treatment implications, and, on the other hand, the association between exogenous infections and the etiology of the disease.
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Affiliation(s)
- Francesco Vito Mandarino
- Division of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
| | - Alberto Barchi
- Division of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Maria Chiara Verga
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy
| | - Daniele Brinch
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
- Gastroenterology & Hepatology Section, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Dario Raimondo
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy
| | - Silvio Danese
- Division of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
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Zhang T, Zhang B, Ma X, Zhang J, Wei Y, Wang F, Tang X. Research trends in the field of the gut-brain interaction: Functional dyspepsia in the spotlight – An integrated bibliometric and science mapping approach. Front Neurosci 2023; 17:1109510. [PMID: 36968499 PMCID: PMC10035075 DOI: 10.3389/fnins.2023.1109510] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 02/22/2023] [Indexed: 03/10/2023] Open
Abstract
ObjectivesThis study aims to perform a bibliometric analysis of functional dyspepsia (FD), which includes visualizing bibliographic information, in order to identify prevailing study themes, topics of interest, contributing journals, countries, institutions, and authors as well as co-citation patterns.MethodsThe Web of Science™ Core Collection Database was used to retrieve all peer-reviewed scientific publications related to FD research. The validated search terms were entered into the “title” and “author keywords” fields, and the results were sorted by publication year from 2006 to 2022. There were no restrictions on language. On 12 February 2023, a manual export of the complete metadata for each original publication and review article was performed. CiteSpace was used to reveal co-authorship, publication, and co-citation patterns to find prominent authors, organizations, countries, and journals in FD research as well as to identify author keywords with strong citation bursts, which could indicate an emerging research area. VOSviewer was used to build the co-occurrence indicator (co-word) to identify the main author keywords on which previous studies focused and to induce clustered scientific landscape for two consecutive periods to identify intriguing areas for future research.ResultsA search of the database retrieved 2,957 documents. There was a wave-like pattern in the number of publications until 2017, after which there was a spike in publication volume. The USA, China, and Japan provided the majority of contributions. In terms of institution, Mayo Clin, Univ Newcastle, and Katholieke Univ Leuven were found to be the prolific institutions. Additionally, the results indicate that eastern Asian researchers contributed significantly to the global knowledge of literature that led other countries; however, Canada, the USA, Australia, England, and Germany were found to have the highest degree of betweenness centrality. Nicholas J. Talley, Jan Tack, Gerald Holtmann, Michael Camilleri, Ken Haruma, and Paul Moayyedi occupied the top positions based on productivity and centrality indicators. Six thematic clusters emerged (Helicobacter pylori infection; pathophysiological mechanisms of FD; extraintestinal co-morbidities and overlap syndromes associated with FD; herbal medicine in FD; diabetic gastroparesis; and dietary factors in FD). “Acupuncture,” “duodenal eosinophilia,” “gut microbiota,” and others were among the author keywords with rising prevalence.ConclusionIn FD research, eastern Asian countries have established themselves as major contributors with the highest publishing productivity; however, research has primarily been driven by North America, Europe, and Australia, where cooperation is generally more active and highly influential scientific results are produced. Our analysis suggests that increased investments, training of human resources, improved infrastructures, and expanded collaborations are essential to improving the quality of FD research in Asia. The emerging author keyword analysis suggests that eosinophil-mast cell axis, gut microbiota, mental disorders, and acupuncture are the key areas that attract researchers’ attention as future research boulevards. There is a highly skewed distribution of research output across Asia, with most focus on complementary and alternative medicine (CAM) coming from Chinese, Japanese, and South Korean centers. However, CAM remains an underexplored area of research in the context of FD, and it deserves greater research efforts in order to obtain quality scientific evidence. Furthermore, we propose that the research framework of CAM should not be limited to dysmotility; rather, it could be interpreted within a more holistic context that includes the brain-gut-microbiota axis, as well as novel concepts such as duodenitis, increased mucosal permeability, and infiltration and activation of eosinophils and mast cells, among others. Overall, we provided bibliometrics-based overviews of relevant literature to researchers from different backgrounds and healthcare professionals to provide an in-depth overview of major trends in FD research.
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Affiliation(s)
- Tai Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Beihua Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiangxue Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaqi Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuchen Wei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Fengyun Wang,
| | - Xudong Tang
- Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Xudong Tang,
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Wei Q, Zhang Q, Wu Y, Han S, Yin L, Zhang J, Gao Y, Shen H, Zhuang J, Chu J, Liu J, Wei Y. Analysis of bacterial diversity and community structure in gastric juice of patients with advanced gastric cancer. Discov Oncol 2023; 14:7. [PMID: 36662326 PMCID: PMC9860007 DOI: 10.1007/s12672-023-00612-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/09/2023] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The occurrence and development of gastric cancer are related to microorganisms, which can be used as potential biomarkers of gastric cancer. OBJECTIVE To screen the microbiological markers of gastric cancer from the microorganisms of gastric juice. METHODS Gastric juice samples were collected from 61 healthy people and 78 patients with gastric cancer (48 cases of early gastric cancer and 30 cases of advanced gastric cancer). The bacterial 16 S rRNA V1-V4 region of gastric juice samples was sequenced. The Shannon index, Simpson index, Ace index and Chao index were used to analyze the diversity of gastric juice samples. The RDP classifier Bayesian algorithm was used to analyze the community structure of 97% OTU representative sequences with similar levels. Linear discriminant analysis and ST-test were used to analyze the differences. Six machine learning algorithms, including the logistic regression algorithm, random forest algorithm, neural network algorithm, support vector machine algorithm, Catboost algorithm and gradient lifting tree algorithm, were used to construct risk prediction models for gastric cancer and advanced gastric cancer. RESULTS The microbiota diversity and the abundance of bacteria was different in the healthy group, early gastric cancer and advanced gastric cancer (P < 0.05). The top five abundant bacteria among the three groups were Streptococcus, Rhodococcus, Prevotella, Pseudomonas and Helicobacter. Bacterial flora such as Streptococcus, Rhodococcus and Ochrobactrum were significantly different between the healthy group and the gastric cancer group. The accuracy of the random forest prediction model is the highest (82.73% correct). The bacteria with the highest predictive value included Streptococcus, Lactobacillus and Ochrobactrum. The abundance of bacteria such as Fusobacterium, Capnocytophaga, Atopobium, Corynebacterium was high in the advanced gastric cancer group. CONCLUSION Gastric juice bacteria can be used as potential biomarkers to predict the occurrence and development of gastric cancer.
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Affiliation(s)
- Qiang Wei
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Qi Zhang
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Yinhang Wu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Shuwen Han
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, People's Republic of China
| | - Lei Yin
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Jinyu Zhang
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Yuhai Gao
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Hong Shen
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Jing Zhuang
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China
| | - Jian Chu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Jiang Liu
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China.
| | - Yunhai Wei
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Zhejiang Province, 313000, Huzhou, People's Republic of China.
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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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Koga Y. Microbiota in the stomach and application of probiotics to gastroduodenal diseases. World J Gastroenterol 2022; 28:6702-6715. [PMID: 36620346 PMCID: PMC9813937 DOI: 10.3748/wjg.v28.i47.6702] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/28/2022] [Accepted: 11/25/2022] [Indexed: 12/19/2022] Open
Abstract
The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.
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Affiliation(s)
- Yasuhiro Koga
- Japanese Society for Probiotic Science, Isehara 259-1143, Japan
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18
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Fecal Microbiota Transplantation and Other Gut Microbiota Manipulation Strategies. Microorganisms 2022; 10:microorganisms10122424. [PMID: 36557677 PMCID: PMC9781458 DOI: 10.3390/microorganisms10122424] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.
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19
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Liu D, Wang J, Xie Y. Refractory Helicobacter pylori infection and the gastric microbiota. Front Cell Infect Microbiol 2022; 12:976710. [PMID: 36237432 PMCID: PMC9552320 DOI: 10.3389/fcimb.2022.976710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/15/2022] [Indexed: 12/02/2022] Open
Abstract
Background Curing refractory Helicobacter pylori infection is difficult. In addition, there is currently no research on the gastric microbiota of refractory H. pylori infection. Methods We designed a clinical retrospective study involving 32 subjects divided into three groups: 1. nAGHp.a, treatment-naïve patients with H. pylori infection; 2. nAGHp.b, H. pylori-negative patients; and 3. EFHp.a, patients with refractory H. pylori infection. Gastric mucosal samples from the biobank of our research center were collected for 16S rRNA sequencing analysis and bacterial functions were predicted via PICRUSt. Results There were significant differences between the H. pylori- positive group and the H. pylori-negative group in species diversity, gastric microbiota structure, and bacterial function. The beneficial Lactobacillus in the H. pylori-positive group were significantly enriched compared with those in the refractory H. pylori infection group. The bacterial interaction network diagram suggested that the microbiota interactions in the refractory H. pylori infection group decreased. The gastric microbiota of the refractory H. pylori infection group was enriched in the pathways of metabolism and infectious diseases (energy metabolism, bacterial secretion system, glutathione metabolism, protein folding and associated processing, sulphur metabolism, membrane and intracellular structural molecules, lipopolysaccharide biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis, inorganic ion transport and metabolism, and metabolism of cofactors and vitamins) when compared with the H. pylori-positive group without treatment based on PICRUSt analysis. Conclusion Significant alterations occurred in the gastric microbiota when eradication of H. pylori failed multiple times. A history of eradication of multiple H. pylori infections leads to an imbalance in the gastric mucosal microbiota to a certain extent, which was mainly reflected in the inhibition of the growth of beneficial Lactobacillus in the stomach. Patients with refractory H. pylori infection may be at a higher risk of developing gastric cancer than other H. pylori-positive patients.
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Affiliation(s)
- Dongsheng Liu
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jinyun Wang
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yong Xie
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Yong Xie,
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20
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Black CJ, Paine PA, Agrawal A, Aziz I, Eugenicos MP, Houghton LA, Hungin P, Overshott R, Vasant DH, Rudd S, Winning RC, Corsetti M, Ford AC. British Society of Gastroenterology guidelines on the management of functional dyspepsia. Gut 2022; 71:1697-1723. [PMID: 35798375 PMCID: PMC9380508 DOI: 10.1136/gutjnl-2022-327737] [Citation(s) in RCA: 84] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/21/2022] [Indexed: 01/30/2023]
Abstract
Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research.
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Affiliation(s)
- Christopher J Black
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Peter A Paine
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
- Gastroenterology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Anurag Agrawal
- Doncaster and Bassetlaw Hospitals NHS Trust, Doncaster, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Maria P Eugenicos
- Department of Gastroenterology, University of Edinburgh, Edinburgh, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Pali Hungin
- Primary Care and General Practice, University of Newcastle, Newcastle, UK
| | - Ross Overshott
- Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
| | - Dipesh H Vasant
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
- Neurogastroenterology Unit, Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - Sheryl Rudd
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Richard C Winning
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
- University of Nottingham and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Alexander C Ford
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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21
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Chen B, Yang C, Dragomir MP, Chi D, Chen W, Horst D, Calin GA, Li Q. Association of proton pump inhibitor use with survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Ther Adv Med Oncol 2022; 14:17588359221111703. [PMID: 35860836 PMCID: PMC9290095 DOI: 10.1177/17588359221111703] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 06/15/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies. Results: A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17–1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation. Conclusions: PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.
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Affiliation(s)
- Baoqing Chen
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chen Yang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mihnea P Dragomir
- Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Dongmei Chi
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wenyan Chen
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - David Horst
- Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - George A Calin
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Qiaoqiao Li
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou 510060, China
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22
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Hari S, Burns GL, Hoedt EC, Keely S, Talley NJ. Eosinophils, Hypoxia-Inducible Factors, and Barrier Dysfunction in Functional Dyspepsia. FRONTIERS IN ALLERGY 2022; 3:851482. [PMID: 35769556 PMCID: PMC9234913 DOI: 10.3389/falgy.2022.851482] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 05/13/2022] [Indexed: 11/13/2022] Open
Abstract
Functional dyspepsia (FD) is a highly prevalent disorder of gut-brain interaction (DGBI), previously known as a functional gastrointestinal disorder. Characterized by early satiety, postprandial fullness, and/or epigastric pain or burning, diagnosis depends on positive symptomatology and exclusion of obvious structural diseases. A subtle inflammatory phenotype has been identified in FD patients, involving an increase in duodenal mucosal eosinophils, and imbalances in the duodenal gut microbiota. A dysregulated epithelial barrier has also been well described in FD and is thought to be a contributing factor to the low-grade duodenal inflammation observed, however the mechanisms underpinning this are poorly understood. One possible explanation is that alterations in the microbiota and increased immune cells can result in the activation of cellular stress response pathways to perpetuate epithelial barrier dysregulation. One such cellular response pathway involves the stabilization of hypoxia-inducible factors (HIF). HIF, a transcriptional protein involved in the cellular recognition and adaptation to hypoxia, has been identified as a critical component of various pathologies, from cancer to inflammatory bowel disease (IBD). While the contribution of HIF to subtle inflammation, such as that seen in FD, is unknown, HIF has been shown to have roles in regulating the inflammatory response, particularly the recruitment of eosinophils, as well as maintaining epithelial barrier structure and function. As such, we aim to review our present understanding of the involvement of eosinophils, barrier dysfunction, and the changes to the gut microbiota including the potential pathways and mechanisms of HIF in FD. A combination of PubMed searches using the Mesh terms functional dyspepsia, functional gastrointestinal disorders, disorders of gut-brain interaction, duodenal eosinophilia, barrier dysfunction, gut microbiota, gut dysbiosis, low-grade duodenal inflammation, hypoxia-inducible factors (or HIF), and/or intestinal inflammation were undertaken in the writing of this narrative review to ensure relevant literature was included. Given the findings from various sources of literature, we propose a novel hypothesis involving a potential role for HIF in the pathophysiological mechanisms underlying FD.
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Affiliation(s)
- Suraj Hari
- Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Grace L. Burns
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Newcastle, NSW, Australia
| | - Emily C. Hoedt
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Newcastle, NSW, Australia
| | - Simon Keely
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Newcastle, NSW, Australia
| | - Nicholas J. Talley
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- School of Medicine and Public Health, College of Health, Medicine and Wellbeing, The University of Newcastle, Newcastle, NSW, Australia
- *Correspondence: Nicholas J. Talley
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23
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Liatsos C, Papaefthymiou A, Kyriakos N, Galanopoulos M, Doulberis M, Giakoumis M, Petridou E, Mavrogiannis C, Rokkas T, Kountouras J. Helicobacter pylori, gastric microbiota and gastric cancer relationship: Unrolling the tangle. World J Gastrointest Oncol 2022; 14:959-972. [PMID: 35646287 PMCID: PMC9124990 DOI: 10.4251/wjgo.v14.i5.959] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/12/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
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Affiliation(s)
- Christos Liatsos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Apostolis Papaefthymiou
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
- Gastroenterology, University Hospital of Larissa, Larissa 41336, Greece
| | - Nikolaos Kyriakos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michail Galanopoulos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michael Doulberis
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau 1234, Switzerland
| | - Marios Giakoumis
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Evangelia Petridou
- Department of Microbiology, “Agia Sofia” Paediatric Hospital, Goudi, Athens 11527, Greece
| | - Christos Mavrogiannis
- Gastrointestinal and Liver Unit, Faculty of Nursing, Kifissia General and Oncology Hospital, Kaliftaki, N.Kifisia 14564, Greece
| | - Theodore Rokkas
- Gastroenterological Clinic, Henry Dunant Hospital, Athens 11525, Greece
| | - Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 41336, Macedonia, Greece
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24
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Filardo S, Scalese G, Virili C, Pontone S, Di Pietro M, Covelli A, Bedetti G, Marinelli P, Bruno G, Stramazzo I, Centanni M, Sessa R, Severi C. The Potential Role of Hypochlorhydria in the Development of Duodenal Dysbiosis: A Preliminary Report. Front Cell Infect Microbiol 2022; 12:854904. [PMID: 35521214 PMCID: PMC9062108 DOI: 10.3389/fcimb.2022.854904] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 03/28/2022] [Indexed: 01/04/2023] Open
Abstract
In recent years, the role of gastric and duodenal microbiota has acquired increasing importance in the homeostasis of the host, although, to date, most evidence concern the faecal microbiota. Indeed, the gastric, and duodenal microbiota are challenging to study, due to gastric acid, bile, digestive enzymes, and rapid transit time. Specifically, the gastric acid environment may influence their bacterial composition since the acid barrier protects against orally ingested microorganisms and leads to their inactivation before reaching the intestine. The aim of this study was to assess a correlation between intragastric pH and gastric as well as intestinal microbiota of patients with histologic gastric alterations. pH was measured in the gastric juice and the bacterial composition in gastric and duodenal biopsies and faecal samples, was investigated via 16s rRNA gene sequencing. The main result is the direct correlation of duodenal microbiota biodiversity, via alpha diversity measures, with intragastric pH values. In particular, patients with hypochlorhydria showed increased duodenal microbiota biodiversity, higher intragastric pH values being prevalent in patients with chronic atrophic gastritis. Lastly, the latter was also strongly associated to the presence of oral bacteria, like Rothia mucilaginosa, Streptococcus salivarius and Granulicatella adiacens, in the duodenal microbiota. In conclusions, our results suggest a low-acid gastric environment as a contributive factor for duodenal dysbiosis, potentially leading to the development of pathological conditions of the gastrointestinal tract.
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Affiliation(s)
- Simone Filardo
- Department of Public Health and Infectious Diseases, University of Rome “Sapienza”, Rome, Italy
- *Correspondence: Simone Filardo,
| | - Giulia Scalese
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
| | - Camilla Virili
- Department of Medico-surgical Sciences and Biotechnologies, University of Rome “Sapienza”, Latina, Italy
| | - Stefano Pontone
- Department of Surgical Sciences, University of Rome “Sapienza”, Rome, Italy
| | - Marisa Di Pietro
- Department of Public Health and Infectious Diseases, University of Rome “Sapienza”, Rome, Italy
| | - Antonio Covelli
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
| | - Giorgio Bedetti
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
| | - Paride Marinelli
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
| | - Giovanni Bruno
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
| | - Ilaria Stramazzo
- Department of Medico-surgical Sciences and Biotechnologies, University of Rome “Sapienza”, Latina, Italy
| | - Marco Centanni
- Department of Medico-surgical Sciences and Biotechnologies, University of Rome “Sapienza”, Latina, Italy
- Endocrine Unit, Azienda Unità Sanitaria Locale (AUSL) Latina, Latina, Italy
| | - Rosa Sessa
- Department of Public Health and Infectious Diseases, University of Rome “Sapienza”, Rome, Italy
| | - Carola Severi
- Department of Translational and Precision Medicine, University of Rome “Sapienza”, Rome, Italy
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25
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Kim SH. [Duodenal Microbiome and Its Clinical Implications in Functional Dyspepsia]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2022; 79:91-98. [PMID: 35342166 DOI: 10.4166/kjg.2022.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/04/2022] [Accepted: 03/15/2022] [Indexed: 11/03/2022]
Abstract
Functional dyspepsia is one of the most common functional gastrointestinal disorders with chronic bothersome epigastric pain or postprandial fullness without a definite organic cause. Despite its high clinical burden, the treatment modalities for modulating impaired motor dysfunction and visceral hypersensitivity have been unsatisfactory. Recently, studies demonstrating low-grade inflammation and dysbiosis of the duodenal mucosa as potential triggers of the disease have attracted attention. Observations, such as an increase in the proportion of oral commensal bacteria in the duodenal mucosa, such as Streptococcus species, highlight the importance of bacterial ecology in developing symptoms of functional dyspepsia. In the near future, anti-inflammatory drugs and probiotics that modulate the host-microbiome interaction are expected to emerge to treat functional dyspepsia.
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Affiliation(s)
- Sang Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
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26
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Wauters L, Tito RY, Ceulemans M, Lambaerts M, Accarie A, Rymenans L, Verspecht C, Toth J, Mols R, Augustijns P, Tack J, Vanuytsel T, Raes J. Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia. Int J Mol Sci 2021; 22:ijms222413609. [PMID: 34948413 PMCID: PMC8708077 DOI: 10.3390/ijms222413609] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022] Open
Abstract
Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.
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Affiliation(s)
- Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Raúl Y. Tito
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Matthias Ceulemans
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Maarten Lambaerts
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Alison Accarie
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Leen Rymenans
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Chloë Verspecht
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Joran Toth
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Raf Mols
- Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium; (R.M.); (P.A.)
| | - Patrick Augustijns
- Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium; (R.M.); (P.A.)
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
- Correspondence: (T.V.); (J.R.)
| | - Jeroen Raes
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
- Correspondence: (T.V.); (J.R.)
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Abstract
Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (n = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. β-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered β-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. IMPORTANCE The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.
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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: 15] [Impact Index Per Article: 3.8] [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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Fabbri C, Coluccio C, Binda C, Fugazza A, Anderloni A, Tarantino I. Lumen-apposing metal stents: How far are we from standardization? An Italian survey. Endosc Ultrasound 2021; 11:59-67. [PMID: 34677143 PMCID: PMC8887041 DOI: 10.4103/eus-d-21-00015] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
Abstract
Background and Objectives: EUS-guided transluminal drainage has increasingly developed, especially after the era of lumen-apposing metal stent (LAMS): a fully covered, barbell-shaped, metal stent with anti-migratory properties allowing direct therapeutic interventions through a wide and short channel. The aim of this survey is to investigate the current management of patients undergoing LAMS placement nationwide. Materials and Methods: Forty-eight questions were submitted to Italian centers about expertise, peri- and intra-procedural aspects, budget/refund, and future perspectives. Statistical analyzer was SPSS®. Results: Thirty-six centers completed the survey. Indications for LAMS positioning are pancreatic fluid collection drainage (PFCD, 97.2%), biliary drainage (BD, 80.5%), gallbladder drainage (GBD, 75%), and gastroentero-anastomosis (GEA, 19.4%). A total of 77.7% of the endoscopists perform only on-label procedures and 22.2% both on-label and off-label. 38.8% attended a training preliminary course, 27.7% were just supported by an expert, 22.2% had both the opportunities, and 8.3% none of them. Management of antiplatelets and sedation protocol is very heterogeneous. Only 50% involves a multidisciplinary meeting and 30.5% has a specialized clinic for follow-up. Acid suppression is usually continued after PFCD. The type and timing of postprocedural imaging varies widely. 8.3% of the endoscopists work without fluoroscopy. Refund for LAMS is mostly not guaranteed. Main future growing indications appear to be BD, GBD, and GEA (69.4%, 55.5%, and 55.5%, respectively). Conclusions: This is the first survey assessing the state of the art on LAMS almost 10 years after their advent. There are currently wide variations in practice nationwide, which demonstrates a pressing need to define technical, qualitative, and peri-procedural requirements to carry out this procedure, toward a standardization.
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Affiliation(s)
- Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì Cesena Hospitals, AUSL Romagna, Italy
| | - Chiara Coluccio
- Gastroenterology and Digestive Endoscopy Unit, Forlì Cesena Hospitals, AUSL Romagna, Italy
| | - Cecilia Binda
- Gastroenterology and Digestive Endoscopy Unit, Forlì Cesena Hospitals, AUSL Romagna, Italy
| | - Alessandro Fugazza
- Digestive Endoscopy Unit, Humanitas Clinical and Research Center-IRCCS, via Manzoni, Rozzano (MI), Italy
| | - Andrea Anderloni
- Digestive Endoscopy Unit, Humanitas Clinical and Research Center-IRCCS, via Manzoni, Rozzano (MI), Italy
| | - Ilaria Tarantino
- Department of Diagnostic and Therapeutic Services, Endoscopy Service, IRCCS-ISMETT, Palermo, Italy
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30
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Mao LQ, Zhou YL, Wang SS, Chen L, Hu Y, Yu LM, Xu JM, Lyu B. Impact of Helicobacter pylori eradication on the gastric microbiome. Gut Pathog 2021; 13:60. [PMID: 34645495 PMCID: PMC8513236 DOI: 10.1186/s13099-021-00460-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 10/07/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Helicobacter pylori (Hp) eradication has been used for many years. Yet, the impact of this eradication on the normal gastric microflora is not well understood. In this study, we explored the effect of eradication on the stomach microbial community and its recovery after successful Hp eradication. METHODS Among the 89 included patients, 23, 17, 40, and 9 were included in the Hp-negative, Hp-positive, successful eradication, and failed eradication groups, respectively. Four subgroups were further determined according to disease status (Hp-negative chronic gastritis [N-CG], Hp-negative atrophic gastritis [N-AG], successful-eradication chronic gastritis [SE-CG], and atrophic gastritis with successful eradication [SE-AG]). During the endoscopic examination, one piece of gastric mucosa tissue was obtained from the lesser curvature side of the gastric antrum and gastric corpus, respectively. In addition, 16S rDNA gene sequencing was used to analyze the gastric mucosal microbiome. RESULTS In the Hp-negative group, the gastric microbiota was dominated by five phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. After successfully eradicating Hp, the bacterial flora in the stomach recovered to a considerable extent. In the failed eradication group, the flora was similar to the flora in Hp-positive subjects based on the alpha and beta diversities. Among the groups, Curvibacter and Acinetobacter were enriched in the presence of Hp (i.e., failed eradication and Hp-positive groups), suggesting that these two genera could be used as biomarkers in the symbiotic flora in the presence of Hp. SE-CG was characterized by an increase in Firmicutes taxa and a decrease in Proteobacteria taxa compared with N-CG. SE-AG was characterized by a decrease in Firmicutes relative to N-AG. Finally, no differences were found in the pairwise comparisons of nitrate and nitrite reductase functions of the microflora among the four subgroups. CONCLUSIONS After Hp infection, the diversity and relative abundance of gastric microflora were significantly decreased. Yet, gastric microbiota could be partially restored to the Hp-negative status after eradication. Still, this effect was incomplete and might contribute to the long-term risks.
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Affiliation(s)
- Li-Qi Mao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Gastroenterology, The First People's Hospital of Huzhou, The First Affiliated Hospital of Huzhou Teachers College, Huzhou, China
| | - Yan-Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuang-Shuang Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, China
| | - Lin Chen
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yue Hu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Lei-Min Yu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Gastroenterology, Guangxing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Jing-Ming Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Lyu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
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Gomez-Ramirez U, Valencia-Mayoral P, Mendoza-Elizalde S, Murillo-Eliosa JR, Solórzano Santos F, Contreras-Rodríguez A, Zúñiga G, Aguilar-Rodea P, Jiménez-Rojas VL, Vigueras Galindo JC, Salazar-García M, Velázquez-Guadarrama N. Role of Helicobacter pylori and Other Environmental Factors in the Development of Gastric Dysbiosis. Pathogens 2021; 10:1203. [PMID: 34578235 PMCID: PMC8467233 DOI: 10.3390/pathogens10091203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/26/2021] [Accepted: 09/08/2021] [Indexed: 11/17/2022] Open
Abstract
Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities.
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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.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
- Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Pedro Valencia-Mayoral
- Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (P.V.-M.); (J.R.M.-E.)
| | - Sandra Mendoza-Elizalde
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
| | - Juan Rafael Murillo-Eliosa
- Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (P.V.-M.); (J.R.M.-E.)
| | - Fortino Solórzano Santos
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
| | - Araceli Contreras-Rodríguez
- Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Gerardo Zúñiga
- Laboratorio de Variación Biológica y Evolución, Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Pamela Aguilar-Rodea
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
| | - Verónica Leticia Jiménez-Rojas
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
| | - Juan Carlos Vigueras Galindo
- Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (U.G.-R.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
| | - Marcela Salazar-García
- Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis 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.); (S.M.-E.); (F.S.S.); (P.A.-R.); (V.L.J.-R.); (J.C.V.G.)
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Li ZP, Liu JX, Lu LL, Wang LL, Xu L, Guo ZH, Dong QJ. Overgrowth of Lactobacillus in gastric cancer. World J Gastrointest Oncol 2021; 13:1099-1108. [PMID: 34616515 PMCID: PMC8465450 DOI: 10.4251/wjgo.v13.i9.1099] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/30/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.
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Affiliation(s)
- Zhi-Peng Li
- Department of Gastroenterology and Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Ju-Xin Liu
- Clinical Laboratories, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China
| | - Lin-Lin Lu
- Department of Gastroenterology and Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Li-Li Wang
- Department of Gastroenterology and Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Lin Xu
- Department of Gastroenterology and Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Zong-Hao Guo
- Department of Clinical Medicine, Jining Medical University, Jining 272000, Shandong Province, China
| | - Quan-Jiang Dong
- Department of Gastroenterology and Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
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Zanza C, Romenskaya T, Thangathurai D, Ojetti V, Saviano A, Abenavoli L, Robba C, Cammarota G, Franceschi F, Piccioni A, Longhitano Y. Microbiome in Critical illness: An Unconventional and Unknown Ally. Curr Med Chem 2021; 29:3179-3188. [PMID: 34525908 DOI: 10.2174/0929867328666210915115056] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 08/10/2021] [Accepted: 08/15/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during the hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of variuos medications or alterations in the intestinal wall which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, liberation of free radicals. OBJECTIVE This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review were reviewed the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically. In addition, we considered it necessary to review the literature to report the current best treatment strategies to prevent the infection spread which can bring systemic infections in patients admitted to ICU. MATERIAL AND METHODS This review has been written to answer at three main questions: what are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases on a day-to-day basis? What are the main dysbiosis' systemic abnormalities? What are the modern strategies that are used in the ICU patients to prevent the infection spread? Using the combination of following keywords: microbiota and ICU, ICU and gut, microbiota and critical illness, microbiota and critical care, microbiota and sepsis, microbiota and infection, gastrointestinal immunity,in the Cochrane Controlled Trials Register, the Cochrane Library, medline and pubmed, google scholar, ovid/wiley. Finally, we reviewed and selected 72 articles. We also consulted the site ClinicalTrials.com to find out studies that are recently conducted or ongoing. RESULTS The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or by stimulating lymphocytes T helper-2 produces anti-inflammatory cytokines. But these defenses can be altered following a hospitalization in ICU and lead to serious complications such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), Systemic infection and multiple organ failure (MOF), but also in the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients. CONCLUSION The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frailty in intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU associated complications. By using the resources, we have available, such as probiotics, symbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.
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Affiliation(s)
- Christian Zanza
- Department of Emergency Medicine Division, Policlinico Gemelli/IRCCS- University of Catholic of Sacred Heart, Rome. Italy
| | - Tatsiana Romenskaya
- Department of Anesthesia and Critical Care Medicine - AON St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria. Italy
| | - Duraiyah Thangathurai
- Department of Anesthesiology - Keck Medical School of University of Southern California, Los Angeles. United States
| | - Veronica Ojetti
- Department of Emergency Medicine Division, Policlinico Gemelli/IRCCS- University of Catholic of Sacred Heart, Rome. Italy
| | - Angela Saviano
- Department of Emergency Medicine Division, Policlinico Gemelli/IRCCS- University of Catholic of Sacred Heart, Rome. Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University "Magna Graecia", Catanzaro. Italy
| | - Chiara Robba
- Department of Surgical Sciences and Diagnostic Integrated, University of Genoa. Italy
| | - Gianmaria Cammarota
- Department of Medicine and Surgery, Section of Anaesthesia, Analgesia, and Intensive Care, University of Perugia, Perugia. Italy
| | - Francesco Franceschi
- Department of Emergency Medicine Division, Policlinico Gemelli/IRCCS- University of Catholic of Sacred Heart, Rome. Italy
| | - Andrea Piccioni
- Department of Emergency Medicine Division, Policlinico Gemelli/IRCCS- University of Catholic of Sacred Heart, Rome. Italy
| | - Yaroslava Longhitano
- Foundation of "Ospedale Alba-Bra" and Department of Emergency Medicine, Anesthesia and Critical Care Medicine, Michele and Pietro Ferrero Hospital, Verduno. Italy
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Lee KJ. The Usefulness of Symptom-based Subtypes of Functional Dyspepsia for Predicting Underlying Pathophysiologic Mechanisms and Choosing Appropriate Therapeutic Agents. J Neurogastroenterol Motil 2021; 27:326-336. [PMID: 34210898 PMCID: PMC8266502 DOI: 10.5056/jnm21042] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/01/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Functional dyspepsia (FD) is considered to be a heterogeneous disorder with different pathophysiological mechanisms or pathogenetic factors. In addition to traditional mechanisms, novel concepts regarding pathophysiologic mechanisms of FD have been proposed. Candidates of therapeutic agents based on novel concepts have also been suggested. FD is a symptom complex and currently diagnosed by symptom-based Rome criteria. In the Rome criteria, symptom-based subtypes of FD including postprandial distress syndrome and epigastric pain syndrome are recommended to be used, based on the assumption that each subtype is more homogenous in terms of underlying pathophysiologic mechanisms than FD as a whole. In this review, the usefulness of symptombased subtypes of FD for predicting underlying pathophysiologic mechanisms and choosing appropriate therapeutic agents was evaluated. Although several classic pathophysiologic mechanisms are suggested to be associated with individual dyspeptic symptoms, symptom-based subtypes of FD are not specific for a certain pathogenetic factor or pathophysiologic mechanism, and may be frequently associated with multiple pathophysiologic abnormalities. Novel concepts on the pathophysiology of FD show complex interactions between pathophysiologic mechanisms and pathogenetic factors, and prediction of underlying mechanisms of individual patients simply by the symptom pattern or symptom-based subtypes may not be accurate in a considerable proportion of cases. Therefore, subtyping by the Rome criteria appears to have limited value to guide therapeutic strategy, suggesting that the addition of objective parameters or subclassification reflecting physiologic or pathologic tests may be necessary for the targeted therapeutic approaches, particularly when therapeutic agents targeting novel mechanisms are available.
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Affiliation(s)
- Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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35
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Profiling the Gastrointestinal Microbiota. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2021; 2283:83-92. [PMID: 33765312 DOI: 10.1007/978-1-0716-1302-3_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
In this chapter, we provide a methodological description of the process to perform gastrointestinal (GIT) microbiota profiling on human stool samples. The process includes: (i) collection of feces, (ii) isolation of DNA from fecal community bacteria, (iii) selection of both 16S rDNA sequencing target and next-generation sequencing platform, and (iv) analysis and interpretation of sequence data. The process culminates into a comprehensive report on the GIT microbiota composition and structure that may translate into clinically actionable results.
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Jagdish BR, Kilgore WR. The Relationship Between Functional Dyspepsia, PPI Therapy, and the Gastric Microbiome. Kans J Med 2021; 14:136-140. [PMID: 34084274 PMCID: PMC8158412 DOI: 10.17161/kjm.vol1414831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 02/17/2021] [Indexed: 12/28/2022] Open
Affiliation(s)
- Balaji R Jagdish
- Kansas City University of Medicine and Biosciences, Kansas City, MO
| | - William R Kilgore
- Ascension Via Christi, Wichita, KS.,Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
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37
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Durán C, Ciucci S, Palladini A, Ijaz UZ, Zippo AG, Sterbini FP, Masucci L, Cammarota G, Ianiro G, Spuul P, Schroeder M, Grill SW, Parsons BN, Pritchard DM, Posteraro B, Sanguinetti M, Gasbarrini G, Gasbarrini A, Cannistraci CV. Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome. Nat Commun 2021; 12:1926. [PMID: 33771992 PMCID: PMC7997970 DOI: 10.1038/s41467-021-22135-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 02/24/2021] [Indexed: 12/11/2022] Open
Abstract
The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.
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Affiliation(s)
- Claudio Durán
- Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Center for Systems Biology Dresden (CSBD), Cluster of Excellence Physics of Life (PoL), Department of Physics, Technische Universität Dresden, Dresden, Germany
| | - Sara Ciucci
- Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Center for Systems Biology Dresden (CSBD), Cluster of Excellence Physics of Life (PoL), Department of Physics, Technische Universität Dresden, Dresden, Germany
| | - Alessandra Palladini
- Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Center for Systems Biology Dresden (CSBD), Cluster of Excellence Physics of Life (PoL), Department of Physics, Technische Universität Dresden, Dresden, Germany
- Paul Langerhans Institute Dresden, Helmholtz Zentrum Munchen, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Umer Z Ijaz
- Department of Infrastructure and Environment University of Glasgow, School of Engineering, Glasgow, UK
| | - Antonio G Zippo
- Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan, Italy
| | | | - Luca Masucci
- Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Internal Medicine and Gastroenterology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Internal Medicine and Gastroenterology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Pirjo Spuul
- Department of Chemistry and Biotechnology, Division of Gene Technology, Tallinn University of Technology, Tallinn, 12618, Estonia
| | - Michael Schroeder
- Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany
| | - Stephan W Grill
- Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Bryony N Parsons
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - D Mark Pritchard
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
- Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Brunella Posteraro
- Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Giovanni Gasbarrini
- Internal Medicine and Gastroenterology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carlo Vittorio Cannistraci
- Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Center for Systems Biology Dresden (CSBD), Cluster of Excellence Physics of Life (PoL), Department of Physics, Technische Universität Dresden, Dresden, Germany.
- Center for Complex Network Intelligence (CCNI) at Tsinghua Laboratory of Brain and Intelligence (THBI), Department of Biomedical Engineering, Tsinghua University, Beijing, China.
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Wu J, Zhou X, Dou Z, Wu T, Liu R, Sui W, Zhang M. Different Molecular Weight Black Garlic Melanoidins Alleviate High Fat Diet Induced Circadian Intestinal Microbes Dysbiosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:3069-3081. [PMID: 33661003 DOI: 10.1021/acs.jafc.0c07723] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The purpose of this study is to explore the effects of different molecular weight black garlic melanoidins (MLDs) on high fat diet (HFD) induced dysrhythmia of intestinal microorganisms. The results showed that a HFD disturbed the periodic fluctuation of the gut microbiome and that oral gavage of low molecular weight melanoidin (LMM) or high molecular weight melanoidin (HMM) reversed these cyclical variations in part, which resulted in an increase in the number of bacteria producing short-chain fatty acids (SCFAs) and a decrease in the oscillation of inflammation-related bacteria within a specific time period over the course of 1 day. Moreover, structural analysis showed different structure characterizations of LMM and HMM, which are related to the differences in flora oscillation. Therefore, the data showed that LMM and HMM relieve the circadian rhythm disorder of intestinal microbiota induced by a HFD in mice, which supported the further study of MLDs as a new dietary assistant strategy to improve chronic diseases.
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Affiliation(s)
- Jianfu Wu
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Xiaodan Zhou
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Zishan Dou
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Tao Wu
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Rui Liu
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Wenjie Sui
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
| | - Min Zhang
- State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China
- Tianjin Agricultural University, Tianjin 300384, PR China
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Barra WF, Sarquis DP, Khayat AS, Khayat BCM, Demachki S, Anaissi AKM, Ishak G, Santos NPC, Dos Santos SEB, Burbano RR, Moreira FC, de Assumpção PP. Gastric Cancer Microbiome. Pathobiology 2021; 88:156-169. [PMID: 33588422 DOI: 10.1159/000512833] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 11/04/2020] [Indexed: 12/24/2022] Open
Abstract
Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the "top 6" genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.
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Affiliation(s)
| | | | - André Salim Khayat
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.,Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil
| | | | - Samia Demachki
- Unidade Laboratorial de Anatomia Patológica, Universidade Federal do Pará, Belém, Brazil
| | - Ana Karyssa Mendes Anaissi
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.,Unidade Laboratorial de Anatomia Patológica, Universidade Federal do Pará, Belém, Brazil
| | - Geraldo Ishak
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.,Serviço de Cirurgia Geral e do Aparelho Digestivo, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil
| | | | | | - Rommel Rodriguez Burbano
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.,Hospital Ophir Loyola, Belém, Brazil
| | | | - Paulo Pimentel de Assumpção
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil, .,Serviço de Cirurgia Geral e do Aparelho Digestivo, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil,
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40
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Sbeit W, Kadah A, Shahin A, Abed N, Haddad H, Jabbour A, Said Ahmad H, Pellicano R, Khoury T, Mari A. Predictors of in-hospital mortality among patients with clostridium difficile infection: a multicenter study. Minerva Med 2021; 112:124-129. [PMID: 33205642 DOI: 10.23736/s0026-4806.20.07139-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI)-associated mortality is a major global health concern. Several clinical and laboratory parameters have been linked to poor prognosis in patients with CDI. In the current study, we aimed to assess the rate of in-hospital mortality among Israeli CDI patients and to look for clinical and laboratory parameters associated to death. METHODS We performed a multicenter retrospective study enrolling all patients above 18-years old who were hospitalized for CDI or with diagnosis made during hospitalization in two regional, teaching hospitals in the north of Israel (Galilee Medical Center, Nahariya and the Nazareth Hospital, Nazareth, Israel), from January 1, 2015 until January 1, 2020. All files of eligible patients were reviewed for demographic (age, gender), medical history and laboratory tests. RESULTS Overall, we included in the study 180 patients, among them 56 died in hospital due to CDI (group A) while 124 survived (group B). The average age in groups A and B was 77.02±13 vs. 71.5±19.1, respectively. On univariate analysis, several clinical and laboratory parameters were associated with in-hospital mortality, including: advanced age, renal failure, antibiotics treatment while on treatment for CDI, need for mechanical ventilation, level of hemoglobin, white blood cells (WBC) and neutrophils count, neutrophil/lymphocyte ratio, serum level of albumin, creatinine and C reactive protein. On multivariate logistic regression analysis, only 4 parameters showed statistically significant association with in-hospital mortality, including age (odds ratio [OR]: 6.97, 95%confidence interval [CI]: 4.94-8.72, P=0.003), renal failure (OR: 3.72, 95% CI: 1.22-11.24, P=0.02), WBC count (OR: 1.09, 95% CI: 1.02-1.16, P=0.008), and lower albumin level (OR: 47.62, 95% CI: 10.31-200, P<0.0001). CONCLUSIONS In this retrospective, multicenter study, age, serum albumin level, leucocytes count, and renal failure were the main predictors of in-hospital mortality in patients with CDI. Thus, antibiotic use should be weighed carefully in elderly comorbid patients, at increased risk of mortality from CDI .Prospective multicenter randomized studies investigating the effect of albumin infusion on in-hospital death of CDI patients are needed, thus enabling us to direct monitoring and treatment accordingly.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Anas Kadah
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Amir Shahin
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Nizar Abed
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Haya Haddad
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital EMMS, Nazareth, Israel
| | - Adel Jabbour
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
- Laboratory of Medicine, The Nazareth Hospital EMMS, Nazareth, Israel
| | - Helal Said Ahmad
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
- Unit of Gastroenterology and Endoscopy, The Nazareth Hospital EMMS, Nazareth, Israel
| | | | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Amir Mari
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel -
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
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41
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Cervantes J, Michael M, Hong BY, Springer A, Guo H, Mendoza B, Zeng M, Sundin O, McCallum R. Investigation of oral, gastric, and duodenal microbiota in patients with upper gastrointestinal symptoms. J Investig Med 2020; 69:jim-2020-001642. [PMID: 33335025 DOI: 10.1136/jim-2020-001642] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2020] [Indexed: 12/13/2022]
Abstract
Disease-associated alterations of the intestinal microbiota composition, known as dysbiosis, have been well described in several functional gastrointestinal (GI) disorders. Several studies have described alterations in the gastric microbiota in functional dyspepsia, but very few have looked at the duodenum.Here, we explored the upper GI tract microbiota of inpatients with upper GI dyspeptic symptoms, and compared them to achalasia controls, as there is no indication for an esophagogastroduodenoscopy in healthy individuals.We found differences in the microbiota composition at the three sites evaluated (ie, saliva, stomach and duodenum). Changes observed in patients with dyspepsia included an increase in Veillonella in saliva, an oral shift in the composition of the gastric microbiota, and to some degree in the duodenum as well, where an important abundance of anaerobes was observed. Metabolic function prediction identified greater anaerobic metabolism in the stomach microbial community of patients with dyspepsia. Proton pump inhibitor use was not associated with any particular genus. Co-abundance analysis revealed Rothia as the main hub in the duodenum, a genus that significantly correlated with the relative abundance of Clostridium, Haemophilus, and ActinobacillusWe conclude that patients with upper GI symptoms consistent with dyspepsia have alterations in the microbiota of saliva, the stomach, and duodenum, which could contribute to symptoms of functional GI disorders.
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Affiliation(s)
- Jorge Cervantes
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Majd Michael
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Bo-Young Hong
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
| | - Aden Springer
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Hua Guo
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Burgandy Mendoza
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Mingtao Zeng
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | | | - Richard McCallum
- Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
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Plomer M, Iii Perez M, Greifenberg DM. Effect of Bacillus clausii Capsules in Reducing Adverse Effects Associated with Helicobacter pylori Eradication Therapy: A Randomized, Double-Blind, Controlled Trial. Infect Dis Ther 2020; 9:867-878. [PMID: 32897519 PMCID: PMC7680487 DOI: 10.1007/s40121-020-00333-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Antibiotic treatment can alter the gut microbiome and cause short-term gastrointestinal adverse effects (AEs). This study assessed the efficacy of lyophilized capsules containing 2 × 109 spores of Bacillus clausii (Enterogermina®; Sanofi Synthelabo) in reducing AEs associated with Helicobacter pylori eradication therapy in Italy. METHODS In this randomized, double-blind, single-center, phase IIIB study, 130 adult outpatients with H. pylori infection were assigned to receive one Enterogermina® capsule or placebo three times daily for 2 weeks (1:1). During week 1, all patients received clarithromycin 500 mg, amoxicillin 1 g, and rabeprazole 20 mg twice daily. The primary efficacy outcome was the presence of diarrhea in week 1. RESULTS A total of 130 patients were randomized. The incidence of diarrhea in week 1 was 29% in the B. clausii group and 48% in the placebo group [relative risk (RR) 0.61; 95% confidence interval (CI) 0.39-0.97; p = 0.03]. The incidence of diarrhea remained lower with B. clausii than with placebo in week 2 (RR 0.38; 95% CI 0.14-1.02; p = 0.0422). In week 1, the number of days without diarrhea was significantly higher in the B. clausii group than in the placebo group (6.25 vs. 5.86; p = 0.0304). In both groups, the number of days without diarrhea increased significantly (p < 0.0001) from week 1 to week 2. A total of three AEs occurred in two patients in the placebo group, but none were serious. CONCLUSIONS Compared with placebo, Enterogermina® reduced the incidence of, and the number of days with, diarrhea in patients receiving H. pylori eradication therapy. Enterogermina® was well tolerated.
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Affiliation(s)
- Manuel Plomer
- Consumer Healthcare, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany
| | - Marcos Iii Perez
- Consumer Healthcare, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany
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43
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Suárez-Jaramillo A, Baldeón ME, Prado B, Fornasini M, Cohen H, Flores N, Salvador I, Cargua O, Realpe J, Cárdenas PA. Duodenal microbiome in patients with or without Helicobacter pylori infection. Helicobacter 2020; 25:e12753. [PMID: 32896972 DOI: 10.1111/hel.12753] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/06/2020] [Accepted: 07/25/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection. MATERIALS AND METHODS Thirty-eight biopsies from the proximal duodenum of uninfected and 37 from H pylori-infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2. RESULTS AND CONCLUSIONS At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α-diversity was higher in H pylori-infected individuals than in non-infected ones. In terms of β-diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori-infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.
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Affiliation(s)
| | - Manuel E Baldeón
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Belén Prado
- Instituto de Microbiología, COCIBA, Universidad San Francisco de Quito, Quito, Ecuador
| | - Marco Fornasini
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Henry Cohen
- Facultad de Medicina, Universidad de la República Uruguay, Montevideo, Uruguay
| | - Nancy Flores
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Iván Salvador
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Oswaldo Cargua
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - José Realpe
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Biomédica, Universidad Tecnológica Equinoccial, Quito, Ecuador
| | - Paul A Cárdenas
- Instituto de Microbiología, COCIBA, Universidad San Francisco de Quito, Quito, Ecuador
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Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
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Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
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Kim TJ, Lee H. Clinical Significance of Changes in Gut Microbiome Associated with Use of Proton Pump Inhibitors. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2020. [DOI: 10.7704/kjhugr.2020.0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Proton pump inhibitors (PPIs) are commonly used for the treatment of gastric acid-related disorders, and are generally well tolerated. However, by reducing the secretion of gastric acid in the long term, PPI can increase the risk of inducing an imbalance in the gut microbiome composition. Moreover, gastric hypochlorhydria that is caused by PPIs favors the survival and migration of oral bacteria in the lower part of the gastrointestinal tract, with a possible induction of pro-inflammatory microenvironment. Therefore, gut dysbiosis that is associated with the use of PPI has been found to cause adverse infectious and inflammatory diseases. In this regard, adverse effects of the PPI-related gut dysbiosis have been reported in different observational studies, but their clinical relevance remains unclear. Therefore, the aim of this review was to explore the available data on the PPI-related gut dysbiosis in order to better understand its clinical significance.
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Wang Z, Gao X, Zeng R, Wu Q, Sun H, Wu W, Zhang X, Sun G, Yan B, Wu L, Ren R, Guo M, Peng L, Yang Y. Changes of the Gastric Mucosal Microbiome Associated With Histological Stages of Gastric Carcinogenesis. Front Microbiol 2020; 11:997. [PMID: 32547510 PMCID: PMC7272699 DOI: 10.3389/fmicb.2020.00997] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 04/23/2020] [Indexed: 12/22/2022] Open
Abstract
The changes of gastric microbiome across stages of neoplastic progression remain poorly understood, especially for intraepithelial neoplasia (IN) which has been recognized as a phenotypic bridge between atrophic/intestinal metaplastic lesions and invasive cancer. The gastric microbiota was investigated in 30 healthy controls (HC), 21 non-atrophic chronic gastritis (CG), 27 gastric intestinal metaplasia (IM), 25 IN, and 29 gastric cancer (GC) patients by 16S rRNA gene profiling. The bacterial diversity, and abundances of phyla Armatimonadetes, Chloroflexi, Elusimicrobia, Nitrospirae, Planctomycetes, Verrucomicrobia, and WS3 reduced progressively from CG, through IM, IN to GC. Actinobacteria, Bacteriodes, Firmicutes, Fusobacteria, SR1, and TM7 were enriched in the IN and GC. At the community level, the proportions of Gram-positive and anaerobic bacteria increased in the IN and GC compared to other histological types, whereas the aerobic and facultatively anaerobic bacteria taxa were significantly reduced in GC. Remarkable changes in the gastric microbiota functions were detected after the formation of IN. The reduced nitrite-oxidizing phylum Nitrospirae together with a decreased nitrate/nitrite reductase functions indicated nitrate accumulation during neoplastic progression. We constructed a random forest model, which had a very high accuracy (AUC > 0.95) in predicating the histological types with as low as five gastric bacterial taxa. In summary, the changing patterns of the gastric microbiota composition and function are highly indicative of stages of neoplastic progression.
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Affiliation(s)
- Zikai Wang
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xuefeng Gao
- Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China
| | - Ranran Zeng
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Qiong Wu
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Huaibo Sun
- Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China
| | - Wenming Wu
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xiaomei Zhang
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lili Wu
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Rongrong Ren
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Mingzhou Guo
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
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Tziatzios G, Gkolfakis P, Papanikolaou IS, Mathur R, Pimentel M, Giamarellos-Bourboulis EJ, Triantafyllou K. Gut Microbiota Dysbiosis in Functional Dyspepsia. Microorganisms 2020; 8:691. [PMID: 32397332 PMCID: PMC7285034 DOI: 10.3390/microorganisms8050691] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 04/28/2020] [Accepted: 05/06/2020] [Indexed: 12/12/2022] Open
Abstract
Functional dyspepsia (FD) is one of the most prevalent chronic functional gastrointestinal disorders. Several distinct pathophysiological mechanisms, including gastro duodenal motor disorders, visceral hypersensitivity, brain-gut interactions, duodenal subtle inflammation, and genetic susceptibility, have been implicated in the pathogenesis of the disease, so far. However, emerging evidence suggests that both quantitative and qualitative disturbances of the gastrointestinal microbiota may also be implicated. In this context, several studies have demonstrated differences of the commensal bacterial community between patients with FD and healthy controls, while others have shown that intestinal dysbiosis might associate with disease's symptoms severity. Elucidating these complex interactions constituting the microbiota and host crosstalk, may eventually lead to the discovery of novel, targeted therapeutic approaches that may be efficacious in treating the multiple aspects of the disorder. In this review, we summarize the data of the latest research with focus on the association between gut microbiota alterations and host regarding the pathogenesis of FD.
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Affiliation(s)
- Georgios Tziatzios
- Hepatogastroenterology Unit, Second Department of Internal Medicine—Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, 124 62 Athens, Greece; (G.T.); (I.S.P.)
| | - Paraskevas Gkolfakis
- Department of Gastroenterology Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Ioannis S. Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine—Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, 124 62 Athens, Greece; (G.T.); (I.S.P.)
| | - Ruchi Mathur
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA 90048, USA; (R.M.); (M.P.)
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA 90048, USA; (R.M.); (M.P.)
| | | | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine—Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, 124 62 Athens, Greece; (G.T.); (I.S.P.)
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Nakov R, Segal JP, Settanni CR, Bibbò S, Gasbarrini A, Cammarota G, Ianiro G. Microbiome: what intensivists should know. Minerva Anestesiol 2020; 86:777-785. [PMID: 32368882 DOI: 10.23736/s0375-9393.20.14278-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the Intensive Care Unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.
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Affiliation(s)
- Radislav Nakov
- Department of Gastroenterology, Tsaritsa Yoanna University Hospital, Medical University of Sofia, Sofia, Bulgaria
| | | | - Carlo R Settanni
- Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy -
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Mucosa microbiome of gastric lesions: Fungi and bacteria interactions. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2020; 171:195-213. [PMID: 32475522 DOI: 10.1016/bs.pmbts.2020.03.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Many components of the gastric non-Helicobacter pylori microbiota have been identified recently thanks to advances in DNA sequencing techniques. Several lines of evidence support the hypothesis that the gastric microbiome is essential for gastric disorders such as gastric cancer. Microbial interactions impact the pathophysiology of various gastric disorders. This chapter provides an overview of recent findings regarding general gastric microbial community profiling, microbial interactions in the stomach, and microbial characteristics in various gastric disorders.
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50
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Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther 2020; 51:505-526. [PMID: 31990420 DOI: 10.1111/apt.15604] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 09/03/2019] [Accepted: 11/13/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.
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Affiliation(s)
- Lukas Macke
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Leandra Koletzko
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Peter Malfertheiner
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.,Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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