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Hetta HF, Ahmed R, Ramadan YN, Fathy H, Khorshid M, Mabrouk MM, Hashem M. Gut virome: New key players in the pathogenesis of inflammatory bowel disease. World J Methodol 2025; 15:92592. [DOI: 10.5662/wjm.v15.i2.92592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 11/27/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the intestine. While the mechanism underlying the pathogenesis of IBD is not fully understood, it is believed that a complex combination of host immunological response, environmental exposure, particularly the gut microbiota, and genetic susceptibility represents the major determinants. The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans. The gut virome varies greatly among individuals and is influenced by factors including lifestyle, diet, health and disease conditions, geography, and urbanization. The majority of research has focused on the significance of gut bacteria in the progression of IBD, although viral populations represent an important component of the microbiome. We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
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Affiliation(s)
- Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
- Division of Microbiology, Immunology and Biotechnology, Faculty of pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Rehab Ahmed
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Yasmin N Ramadan
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Hayam Fathy
- Department of Internal Medicine, Division Hepatogastroenterology, Assiut University, Assiut 71515, Egypt
| | - Mohammed Khorshid
- Department of Clinical Research, Egyptian Developers of Gastroenterology and Endoscopy Foundation, Cairo 11936, Egypt
| | - Mohamed M Mabrouk
- Department of Internal Medicine, Faculty of Medicine. Tanta University, Tanta 31527, Egypt
| | - Mai Hashem
- Department of Tropical Medicine, Gastroenterology and Hepatology, Assiut University Hospital, Assiut 71515, Egypt
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2
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Xu Y, Xie R, Weng Y, Fang Y, Tao S, Zhang H, Chen H, Han A, Jiang Q, Liang W. Role and mechanism of gut microbiota-host interactions in the pathogenesis of Crohn's disease. Int J Colorectal Dis 2025; 40:130. [PMID: 40437310 PMCID: PMC12119691 DOI: 10.1007/s00384-025-04917-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/08/2025] [Indexed: 06/01/2025]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic, nonspecific inflammatory bowel disease with a poor prognosis. Despite its increasing incidence, curing CD remains challenging due to its complex etiology and unclear pathogenesis. METHODS A comprehensive PubMed and Web of Science search was conducted using the keywords Crohn's disease, gut microbiota, dysbiosis, pathogenesis and treatment, focusing on studies published between 2014 and 2024. RESULTS Recent studies have demonstrated a close relationship between gut microbiota dysbiosis and the development of CD. Although many dysbioses associated with CD have not yet been proven to be causal or consequential, it has been observed that the gut microbiota in CD patients exhibits reduced diversity, a decrease in beneficial bacteria, and an increase in pathogenic bacteria. These changes may lead to decreased intestinal barrier function, abnormal immune responses, and enhanced inflammatory reactions, which are related to the disease's activity, phenotype, drug treatment efficacy, and postoperative therapeutic outcomes. Therefore, further exploration of the microbiota-host interactions and the pathogenesis of CD, the identification of biomarkers, and the development of targeted strategies for modulating the gut microbiota could offer new avenues for the prevention and treatment of CD. CONCLUSIONS This review highlights the pivotal role of gut microbiota dysbiosis in driving CD pathogenesis and its progression, while underscoring its potential as a therapeutic target through dietary modulation, microbial interventions, and integrative strategies to improve clinical management and prognostic outcomes.
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Affiliation(s)
- Yao Xu
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China
- Health Science Center, Ningbo University, Ningbo, China
| | - Runxiang Xie
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yuqing Weng
- Health Science Center, Ningbo University, Ningbo, China
| | - Yewei Fang
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Shuan Tao
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - He Zhang
- Laboratory Medical School, Bengbu Medical University, Bengbu, China
| | - Huimin Chen
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Axiang Han
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Qi Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
| | - Wei Liang
- Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China.
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3
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Xiao Y, Yue X, Zhang X, Yang Y, Zhang Y, Sun L. The role of bacteriophage in inflammatory bowel disease and its therapeutic potential. Crit Rev Microbiol 2025:1-15. [PMID: 40219702 DOI: 10.1080/1040841x.2025.2492154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 03/25/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.
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Affiliation(s)
- Yuyang Xiao
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xinyu Yue
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xupeng Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yifei Yang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yibo Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Lang Sun
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
- Department of Microbiology, Xiangya School of the Basic Medical Science, Central South University, Changsha, Hunan Province, China
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4
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Mpakosi A, Sokou R, Theodoraki M, Iacovidou N, Cholevas V, Tsantes AG, Liakou AI, Drogari-Apiranthitou M, Kaliouli-Antonopoulou C. The Role of Infant and Early Childhood Gut Virome in Immunity and the Triggering of Autoimmunity-A Narrative Review. Diagnostics (Basel) 2025; 15:413. [PMID: 40002565 PMCID: PMC11854275 DOI: 10.3390/diagnostics15040413] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 02/27/2025] Open
Abstract
Background: The bacterial gut microbiome has been the subject of many studies that have provided valuable scientific conclusions. However, many different populations of microorganisms that interact with each other to maintain homeostasis coexist inside the gut. The gut virome, especially, appears to play a key role in this interactive microenvironment. Intestinal viral communities, including bacteriophages, appear to influence health and disease, although their role has not yet been fully elucidated. In addition, bacteriophages or viruses that infect bacteria regulate bacterial growth, thus shaping the composition of the gut microbiome and affecting the immune system. Infant Gut Virome: The shaping of the gut microbiome during the first years of life has a significant role in the maturation of the infant's immune system. In contrast, early dysbiosis has been associated with chronic, including metabolic and autoimmune, disorders later in life. Purpose: Although viruses have been shown to be potential triggers of autoimmune diseases, there is a gap in the literature regarding the infant gut virome in autoimmunity development. Despite the lack of evidence, this review attempts to summarize and clarify what is known so far about this timely and important topic in the hope that its findings will contribute to future research.
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Affiliation(s)
- Alexandra Mpakosi
- Department of Microbiology, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece
| | - Rozeta Sokou
- Neonatal Intensive Care Unit, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece;
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 11528 Athens, Greece;
| | - Martha Theodoraki
- Neonatal Intensive Care Unit, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece;
| | - Nicoletta Iacovidou
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 11528 Athens, Greece;
| | | | - Andreas G. Tsantes
- Department of Microbiology, Saint Savvas Oncology Hospital, 11522 Athens, Greece;
| | - Aikaterini I. Liakou
- 1st Department of Dermatology-Venereology, “Andreas Sygros” Hospital, Medical School, National and Kapodistrian University of Athens, 16121 Athens, Greece;
| | - Maria Drogari-Apiranthitou
- Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece;
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5
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Debray R, Conover A, Koskella B. Phages indirectly maintain tomato plant pathogen defense through regulation of the commensal microbiome. ISME COMMUNICATIONS 2025; 5:ycaf065. [PMID: 40356878 PMCID: PMC12066413 DOI: 10.1093/ismeco/ycaf065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Revised: 04/14/2025] [Accepted: 04/14/2025] [Indexed: 05/15/2025]
Abstract
As parasites of bacteria, phages can regulate microbiome diversity and composition and may therefore affect susceptibility to pathogens and disease. Many infectious diseases are associated with altered bacteriophage communities, but observational studies alone do not allow us to determine when altered phage community composition is a contributor to disease risk, a response to infection, or simply an indicator of dysbiosis. To address this question directly, we used size-selective filtration to deplete plant-associated microbial communities of phages, then challenged plants with the bacterial pathogen Pseudomonas syringae. Plants with phage-depleted microbiomes were more susceptible to infection, an effect that could not be explained by direct effects of the phage communities on either P. syringae or the plant host. Moreover, the presence of phages was most impactful when the phage communities were isolated from neighboring field locations rather than from the same host plant as the bacteria, possibly suggesting that moderate rates of lysis maintain a community structure that is most resistant to pathogen invasion. Overall, our results support the idea that phage communities contribute to plant defenses by modulating the microbiome.
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Affiliation(s)
- Reena Debray
- Department of Primate Behavior and Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
- Department of Integrative Biology, University of California, Berkeley, 94720 Berkeley, CA, United States
| | - Asa Conover
- Department of Integrative Biology, University of California, Berkeley, 94720 Berkeley, CA, United States
| | - Britt Koskella
- Department of Integrative Biology, University of California, Berkeley, 94720 Berkeley, CA, United States
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6
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Caruso R, Lo BC, Chen GY, Núñez G. Host-pathobiont interactions in Crohn's disease. Nat Rev Gastroenterol Hepatol 2024:10.1038/s41575-024-00997-y. [PMID: 39448837 DOI: 10.1038/s41575-024-00997-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/23/2024] [Indexed: 10/26/2024]
Abstract
The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.
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Affiliation(s)
- Roberta Caruso
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
| | - Bernard C Lo
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Grace Y Chen
- Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Gabriel Núñez
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
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Bernardi F, Ungaro F, D’Amico F, Zilli A, Parigi TL, Massimino L, Allocca M, Danese S, Furfaro F. The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases. Int J Mol Sci 2024; 25:8301. [PMID: 39125870 PMCID: PMC11313478 DOI: 10.3390/ijms25158301] [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: 06/18/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.
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Affiliation(s)
- Francesca Bernardi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, Via Olgettina, 58, 20132 Milan, Italy
| | - Federica Ungaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Luca Massimino
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, Via Olgettina, 58, 20132 Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.B.); (F.U.); (F.D.); (A.Z.); (T.L.P.); (L.M.); (M.A.); (S.D.)
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8
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Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Front Immunol 2024; 15:1386607. [PMID: 38887284 PMCID: PMC11180809 DOI: 10.3389/fimmu.2024.1386607] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/11/2024] [Indexed: 06/20/2024] Open
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.
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Affiliation(s)
- Hayley E. Arron
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Benjamin D. Marsh
- MRCPCH Consultant Paediatric Neurodisability, Exeter, Devon, United Kingdom
| | - Douglas B. Kell
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
| | - M. Asad Khan
- Directorate of Respiratory Medicine, Manchester University Hospitals, Wythenshawe Hospital, Manchester, United Kingdom
| | - Beate R. Jaeger
- Long COVID department, Clinic St Georg, Bad Aibling, Germany
| | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
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9
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Maqsood R, Holland LA, Wu LI, Begnel ER, Adhiambo J, Owiti P, Chohan BH, Gantt S, Kinuthia J, Wamalwa D, Ojee E, Richardson BA, Slyker J, Lehman DA, Lim ES. Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants. RESEARCH SQUARE 2024:rs.3.rs-4257515. [PMID: 38699305 PMCID: PMC11065063 DOI: 10.21203/rs.3.rs-4257515/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that while the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). However, gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.
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10
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Zhang J, Huang YJ, Trapecar M, Wright C, Schneider K, Kemmitt J, Hernandez-Gordillo V, Yoon JY, Poyet M, Alm EJ, Breault DT, Trumper DL, Griffith LG. An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii. NPJ Biofilms Microbiomes 2024; 10:31. [PMID: 38553449 PMCID: PMC10980819 DOI: 10.1038/s41522-024-00501-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 03/11/2024] [Indexed: 04/02/2024] Open
Abstract
Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.
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Affiliation(s)
- Jianbo Zhang
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, Location Academic Medical Center, Amsterdam, the Netherlands.
| | - Yu-Ja Huang
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Martin Trapecar
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Charles Wright
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Kirsten Schneider
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - John Kemmitt
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Jun Young Yoon
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Department of Mechanical Engineering, Yonsei University, Seoul, South Korea
| | - Mathilde Poyet
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Institute of Experimental Medicine, University of Kiel, Kiel, Germany
| | - Eric J Alm
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - David T Breault
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - David L Trumper
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Linda G Griffith
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
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11
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Cao Z, Fan D, Sun Y, Huang Z, Li Y, Su R, Zhang F, Li Q, Yang H, Zhang F, Miao Y, Lan P, Wu X, Zuo T. The gut ileal mucosal virome is disturbed in patients with Crohn's disease and exacerbates intestinal inflammation in mice. Nat Commun 2024; 15:1638. [PMID: 38388538 PMCID: PMC10884039 DOI: 10.1038/s41467-024-45794-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 02/01/2024] [Indexed: 02/24/2024] Open
Abstract
Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.
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Affiliation(s)
- Zhirui Cao
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Dejun Fan
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Gastrointestinal Endoscopy, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Sun
- Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
- Yunnan Province Clinical Research Centre for Digestive Diseases, Kunming, Yunnan, China.
- Yunnan Geriatric Medical Centre, Kunming, Yunnan, China.
| | - Ziyu Huang
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yue Li
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Runping Su
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Feng Zhang
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qing Li
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hongju Yang
- Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Geriatric Medical Centre, Kunming, Yunnan, China
| | - Fen Zhang
- Department of Food Science and Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Yinglei Miao
- Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Centre for Digestive Diseases, Kunming, Yunnan, China
| | - Ping Lan
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaojian Wu
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China.
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Tao Zuo
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China.
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Centre for Faecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
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12
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Grygorcewicz B, Gliźniewicz M, Jabłońska J, Augustyniak A, Olszewska P, Wojciuk B, Miłek D, Serwin N, Czajkowski A, Cecerska-Heryć E, Rakoczy R, Cymbaluk-Płoska A. Bacteriophage-based approach for treatment of urinary tract infections: a quick outlook. APMIS 2024; 132:81-93. [PMID: 38031200 DOI: 10.1111/apm.13362] [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: 06/29/2023] [Accepted: 11/08/2023] [Indexed: 12/01/2023]
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections affecting millions worldwide. The increasing emergence of antibiotic-resistant bacteria has become a serious concern in managing UTIs. Therefore, there is a growing interest in using bacteriophages as an alternative or adjunct therapy for UTIs. Bacteriophages are viruses that infect and kill bacteria, making them a promising tool for treating UTIs caused by antibiotic-resistant bacteria. This article provides a quick outlook on using bacteriophages to treat UTIs. We summarize the current understanding of the biology of bacteriophages, the challenges associated with developing phage-based therapies, and the promising results of several case reports and clinical trials. We also highlight the potential of phage therapy as a valuable tool in the fight against antibiotic-resistant UTIs. This quick outlook on a bacteriophage-based approach for treating UTIs offers a timely and informative summary of the current research in this field.
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Affiliation(s)
- Bartłomiej Grygorcewicz
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
- Department of Chemical and Process Engineering, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Szczecin, Poland
| | - Marta Gliźniewicz
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Joanna Jabłońska
- Department of Chemical and Process Engineering, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Szczecin, Poland
| | - Adrian Augustyniak
- Department of Chemical and Process Engineering, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Szczecin, Poland
- Chair of Building Materials and Construction Chemistry, Technische Universität Berlin, Germany, Berlin, Germany
- Institute of Biology, University of Szczecin, Szczecin, Poland
| | - Patrycja Olszewska
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Bartosz Wojciuk
- Department of Immunology Diagnostics, Chair of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Dominika Miłek
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Natalia Serwin
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Artur Czajkowski
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Elżbieta Cecerska-Heryć
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
- Department of Chemical and Process Engineering, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Szczecin, Poland
| | - Rafał Rakoczy
- Department of Chemical and Process Engineering, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Szczecin, Poland
| | - Aneta Cymbaluk-Płoska
- Department of Reconstructive Surgery and Gynecological Oncology, Pomeranian Medical University in Szczecin, Szczecin, Poland
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13
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Kim SH, Keum B, Kwak S, Byun J, Shin JM, Kim TH. Therapeutic Applications of Extracellular Vesicles in Inflammatory Bowel Disease. Int J Mol Sci 2024; 25:745. [PMID: 38255819 PMCID: PMC10815267 DOI: 10.3390/ijms25020745] [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: 11/29/2023] [Revised: 12/28/2023] [Accepted: 01/02/2024] [Indexed: 01/24/2024] Open
Abstract
The treatment landscape for inflammatory bowel disease (IBD) has undergone substantial advancements with the introduction of biologics. However, a considerable number of patients either show an immediate lack of response or lose responsiveness over time, necessitating the development of innovative and effective treatment approaches. Extracellular vesicles (EVs) are small lipid bilayer-enclosed structures that facilitate cell-to-cell molecular transfer and are integral to the pathogenesis of IBD. They play pivotal roles in maintaining the integrity of the intestinal epithelial barrier and the expulsion of cellular metabolites. The potential use of EVs as drug carriers or therapeutic agents has opened up a plethora of clinical applications. This review investigates the creation and content of EVs, their role in IBD development, and advances in their isolation and analytical techniques. Furthermore, the therapeutic promise they hold for IBD is explored, along with the latest research on their roles as IBD drug delivery systems.
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Affiliation(s)
- Sang Hyun Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (S.H.K.)
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (S.H.K.)
| | - Sooun Kwak
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Junhyoung Byun
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Jae Min Shin
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Tae Hoon Kim
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
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14
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Tun HM, Peng Y, Massimino L, Sin ZY, Parigi TL, Facoetti A, Rahman S, Danese S, Ungaro F. Gut virome in inflammatory bowel disease and beyond. Gut 2024; 73:350-360. [PMID: 37949638 PMCID: PMC10850733 DOI: 10.1136/gutjnl-2023-330001] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/24/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVE The gut virome is a dense community of viruses inhabiting the gastrointestinal tract and an integral part of the microbiota. The virome coexists with the other components of the microbiota and with the host in a dynamic equilibrium, serving as a key contributor to the maintenance of intestinal homeostasis and functions. However, this equilibrium can be interrupted in certain pathological states, including inflammatory bowel disease, causing dysbiosis that may participate in disease pathogenesis. Nevertheless, whether virome dysbiosis is a causal or bystander event requires further clarification. DESIGN This review seeks to summarise the latest advancements in the study of the gut virome, highlighting its cross-talk with the mucosal microenvironment. It explores how cutting-edge technologies may build upon current knowledge to advance research in this field. An overview of virome transplantation in diseased gastrointestinal tracts is provided along with insights into the development of innovative virome-based therapeutics to improve clinical management. RESULTS Gut virome dysbiosis, primarily driven by the expansion of Caudovirales, has been shown to impact intestinal immunity and barrier functions, influencing overall intestinal homeostasis. Although emerging innovative technologies still need further implementation, they display the unprecedented potential to better characterise virome composition and delineate its role in intestinal diseases. CONCLUSIONS The field of gut virome is progressively expanding, thanks to the advancements of sequencing technologies and bioinformatic pipelines. These have contributed to a better understanding of how virome dysbiosis is linked to intestinal disease pathogenesis and how the modulation of virome composition may help the clinical intervention to ameliorate gut disease management.
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Affiliation(s)
- Hein Min Tun
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- JC School of Public Health and Primary Care, Faculty of medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ye Peng
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- JC School of Public Health and Primary Care, Faculty of medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Luca Massimino
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy
| | - Zhen Ye Sin
- JC School of Public Health and Primary Care, Faculty of medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy
- Università Vita-Salute San Raffaele Facoltà di Medicina e Chirurgia, Milano, Italy
| | - Amanda Facoetti
- Università Vita-Salute San Raffaele Facoltà di Medicina e Chirurgia, Milano, Italy
| | | | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy
- Università Vita-Salute San Raffaele Facoltà di Medicina e Chirurgia, Milano, Italy
| | - Federica Ungaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy
- Università Vita-Salute San Raffaele Facoltà di Medicina e Chirurgia, Milano, Italy
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15
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Maqsood R, Holland LA, Wu LI, Begnel ER, Adhiambo J, Owiti P, Chohan BH, Gantt S, Kinuthia J, Wamalwa D, Ojee E, Richardson BA, Slyker J, Lehman DA, Lim ES. Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants. Gut Microbes 2024; 16:2394248. [PMID: 39185682 PMCID: PMC11352790 DOI: 10.1080/19490976.2024.2394248] [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: 02/02/2024] [Revised: 07/26/2024] [Accepted: 08/15/2024] [Indexed: 08/27/2024] Open
Abstract
Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). Gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.
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Affiliation(s)
- Rabia Maqsood
- Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
| | - LaRinda A. Holland
- Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
| | - Lily I. Wu
- Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
| | - Emily R. Begnel
- Department of Global Health, University of Washington, Seattle, WA, USA
| | - Judith Adhiambo
- Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Prestone Owiti
- Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Bhavna H. Chohan
- Department of Global Health, University of Washington, Seattle, WA, USA
- Center of Virus Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Soren Gantt
- Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Centre de Recherche du CHU St-Justine, Montreal, Québec, Canada
| | - John Kinuthia
- Department of Global Health, University of Washington, Seattle, WA, USA
- Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya
| | - Dalton Wamalwa
- Department of Global Health, University of Washington, Seattle, WA, USA
- Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Ednah Ojee
- Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Barbra A. Richardson
- Department of Global Health, University of Washington, Seattle, WA, USA
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Jennifer Slyker
- Department of Global Health, University of Washington, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Dara A. Lehman
- Department of Global Health, University of Washington, Seattle, WA, USA
- Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Efrem S. Lim
- Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
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16
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Bhagchandani T, Nikita, Verma A, Tandon R. Exploring the Human Virome: Composition, Dynamics, and Implications for Health and Disease. Curr Microbiol 2023; 81:16. [PMID: 38006423 DOI: 10.1007/s00284-023-03537-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 10/24/2023] [Indexed: 11/27/2023]
Abstract
Humans are colonized by large number of microorganisms-bacteria, fungi, and viruses. The overall genome of entire viruses that either lives on or inside the human body makes up the human virome and is indeed an essential fraction of the human metagenome. Humans are constantly exposed to viruses as they are ubiquitously present on earth. The human virobiota encompasses eukaryotic viruses, bacteriophages, retroviruses, and even giant viruses. With the advent of Next-generation sequencing (NGS) and ongoing development of numerous bioinformatic softwares, identification and taxonomic characterization of viruses have become easier. The viruses are abundantly present in humans; these can be pathogenic or commensal. The viral communities occupy various niches in the human body. The viruses start colonizing the infant gut soon after birth in a stepwise fashion and the viral composition diversify according to their feeding habits. Various factors such as diet, age, medications, etc. influence and shape the human virome. The viruses interact with the host immune system and these interactions have beneficial or detrimental effects on their host. The virome composition and abundance change during the course of disease and these alterations impact the immune system. Hence, the virome population in healthy and disease conditions influences the human host in numerous ways. This review presents an overview of assembly and composition of the human virome in healthy asymptomatic individuals, changes in the virome profiles, and host-virome interactions in various disease states.
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Affiliation(s)
- Tannu Bhagchandani
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Nikita
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Anjali Verma
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Ravi Tandon
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
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17
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Lawal SA, Voisin A, Olof H, Bording-Jorgensen M, Armstrong H. Diversity of the microbiota communities found in the various regions of the intestinal tract in healthy individuals and inflammatory bowel diseases. Front Immunol 2023; 14:1242242. [PMID: 38022505 PMCID: PMC10654633 DOI: 10.3389/fimmu.2023.1242242] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
The severe and chronic inflammatory bowel diseases (IBD), Crohn disease and ulcerative colitis, are characterized by persistent inflammation and gut damage. There is an increasing recognition that the gut microbiota plays a pivotal role in IBD development and progression. However, studies of the complete microbiota composition (bacteria, fungi, viruses) from precise locations within the gut remain limited. In particular, studies have focused primarily on the bacteriome, with available methods limiting evaluation of the mycobiome (fungi) and virome (virus). Furthermore, while the different segments of the small and large intestine display different functions (e.g., digestion, absorption, fermentation) and varying microenvironment features (e.g., pH, metabolites), little is known about the biogeography of the microbiota in different segments of the intestinal tract or how this differs in IBD. Here, we highlight evidence of the differing microbiota communities of the intestinal sub-organs in healthy and IBD, along with method summaries to improve future studies.
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Affiliation(s)
- Samuel Adefisoye Lawal
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Athalia Voisin
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Hana Olof
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
| | | | - Heather Armstrong
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
- Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
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18
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Abstract
The gut microbiome is a dense and metabolically active consortium of microorganisms and viruses located in the lower gastrointestinal tract of the human body. Bacteria and their viruses (phages) are the most abundant members of the gut microbiome. Investigating their biology and the interplay between the two is important if we are to understand their roles in human health and disease. In this review, we summarize recent advances in resolving the taxonomic structure and ecological functions of the complex community of phages in the human gut-the gut phageome. We discuss how age, diet, and geography can all have a significant impact on phageome composition. We note that alterations to the gut phageome have been observed in several diseases such as inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, and we evaluate whether these phageome changes can directly or indirectly contribute to disease etiology and pathogenesis. We also highlight how lack of standardization in studying the gut phageome has contributed to variation in reported results.
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Affiliation(s)
- Ciara A Tobin
- APC Microbiome Ireland, Cork, Ireland; , ,
- School of Microbiology, University College Cork, Cork, Ireland
| | - Colin Hill
- APC Microbiome Ireland, Cork, Ireland; , ,
- School of Microbiology, University College Cork, Cork, Ireland
| | - Andrey N Shkoporov
- APC Microbiome Ireland, Cork, Ireland; , ,
- School of Microbiology, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
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19
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Marcozzi S, Bigossi G, Giuliani ME, Lai G, Giacconi R, Piacenza F, Malavolta M. Spreading Senescent Cells' Burden and Emerging Therapeutic Targets for Frailty. Cells 2023; 12:2287. [PMID: 37759509 PMCID: PMC10528263 DOI: 10.3390/cells12182287] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/12/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
The spreading of senescent cells' burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.
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Affiliation(s)
- Serena Marcozzi
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
- Scientific Direction, IRCCS INRCA, 60124 Ancona, Italy
| | - Giorgia Bigossi
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
| | - Maria Elisa Giuliani
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
| | - Giovanni Lai
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
| | - Robertina Giacconi
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
| | - Francesco Piacenza
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
| | - Marco Malavolta
- Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, 60121 Ancona, Italy; (S.M.); (G.B.); (M.E.G.); (R.G.); (F.P.)
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20
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Chen X, Mendes BG, Alves BS, Duan Y. Phage therapy in gut microbiome. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 201:93-118. [PMID: 37770177 DOI: 10.1016/bs.pmbts.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Phage therapy, the use of bacteriophage viruses for bacterial infection treatment, has been around for almost a century, but with the increase in antibiotic use, its importance has declined rapidly. There has been renewed interest in revisiting this practice due to the general decline in the effectiveness of antibiotics, combined with improved understanding of human microbiota and advances in sequencing technologies. Phage therapy has been proposed as a clinical alternative to restore the gut microbiota in the absence of an effective treatment. That is due to its immunomodulatory and bactericidal effects against its target bacteria. In the gastrointestinal diseases field, phage therapy has been studied mainly as a promising tool in infectious diseases treatment, such as cholera and diarrhea. However, many studies have been conducted in non-communicable diseases, such as the targeting of adherent invasive Escherichia coli in Crohn's disease, the treatment of Clostridioides difficile in ulcerative colitis, the eradication of Fusobacterium nucleatum in colorectal cancer, the targeting of alcohol-producing Klebsiella pneumoniae in non-alcoholic fatty liver disease, or Enterococcus faecalis in alcohol-associated hepatitis. This review will summarize the changes in the gut microbiota and the phageome in association with some gastrointestinal and liver diseases and highlight the recent scientific advances in phage therapy as a therapeutic tool for their treatment.
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Affiliation(s)
- Xingyao Chen
- Department of Infectious Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Beatriz G Mendes
- Department of Clinical Analysis, Health Sciences Center, Federal University of Santa Catarina, Campus Universitário Trindade, Florianópolis, Santa Catarina, Brazil
| | - Bruno Secchi Alves
- Department of Clinical Analysis, Health Sciences Center, Federal University of Santa Catarina, Campus Universitário Trindade, Florianópolis, Santa Catarina, Brazil
| | - Yi Duan
- Department of Infectious Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
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21
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Weiner A, Turjeman S, Koren O. Gut microbes and host behavior: The forgotten members of the gut-microbiome. Neuropharmacology 2023; 227:109453. [PMID: 36738776 DOI: 10.1016/j.neuropharm.2023.109453] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 01/15/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023]
Abstract
The gut microbiota refers to an entire population of microorganisms that colonize the gut. This community includes viruses, prokaryotes (bacteria and archaea), and eukaryotes (fungi and parasites). Multiple studies in the last decades described the significant involvement of gut bacteria in gut-brain axis communication; however, the involvement of other members of the gut microbiota has been neglected. Recent studies found that these 'forgotten' members of the gut microbiota may also have a role in gut-brain communication, although it is still unclear whether they have a direct effect on the brain or if their effects are mediated by gut bacteria. Here, we provide concrete suggestions for future research to tease out mechanisms of the microbiota-gut-brain axis. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".
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Affiliation(s)
- Ariel Weiner
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Sondra Turjeman
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Omry Koren
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
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22
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Bozomitu L, Miron I, Adam Raileanu A, Lupu A, Paduraru G, Marcu FM, Buga AML, Rusu DC, Dragan F, Lupu VV. The Gut Microbiome and Its Implication in the Mucosal Digestive Disorders. Biomedicines 2022; 10:biomedicines10123117. [PMID: 36551874 PMCID: PMC9775516 DOI: 10.3390/biomedicines10123117] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/26/2022] [Accepted: 11/30/2022] [Indexed: 12/10/2022] Open
Abstract
The gastrointestinal (GI) tract is one of the most studied compartments of the human body as it hosts the largest microbial community including trillions of germs. The relationship between the human and its associated flora is complex, as the microbiome plays an important role in nutrition, metabolism and immune function. With a dynamic composition, influenced by many intrinsic and extrinsic factors, there is an equilibrium maintained in the composition of GI microbiota, translated as "eubiosis". Any disruption of the microbiota leads to the development of different local and systemic diseases. This article reviews the human GI microbiome's composition and function in healthy individuals as well as its involvement in the pathogenesis of different digestive disorders. It also highlights the possibility to consider flora manipulation a therapeutic option when treating GI diseases.
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Affiliation(s)
- Laura Bozomitu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Ingrith Miron
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Anca Adam Raileanu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (A.A.R.); (A.L.)
| | - Ancuta Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (A.A.R.); (A.L.)
| | - Gabriela Paduraru
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Florin Mihai Marcu
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
| | - Ana Maria Laura Buga
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Daniela Carmen Rusu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Felicia Dragan
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
| | - Vasile Valeriu Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
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23
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Characteristics of a novel temperate bacteriophage against Staphylococcus arlettae (vB_SarS_BM31). Int Microbiol 2022; 26:327-341. [PMID: 36336729 PMCID: PMC9638216 DOI: 10.1007/s10123-022-00292-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/25/2022] [Accepted: 10/27/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Staphylococcus arlettae is a rarely reported coagulase-negative staphylococcus (CoNS) isolated from infected humans and livestock. Observing phage-bacteria interaction could improve the understanding of bacterial pathogenetic mechanisms, providing foundational evidence for phage therapy or phage detection. Herein, we aimed to characterise and annotate a novel bacteriophage, vB_SarS_BM31 (BM31), specific to S. arlettae. This bacteriophage was isolated from a milk sample associated with bovine mastitis and collected in the Sichuan Province, China. RESULTS The BM31 genome comprised a linear double-stranded DNA of 42,271 base pair in length with a G + C content of 34.59%. A total of 65 open reading frames (ORFs) were assembled from phage DNA, of which 29 were functionally annotated. These functional genes were divided into four modules: the structural, DNA packing and replication, lysis, and lysogeny modules. Holin (ORF25), lysin (ORF26), and integrase (ORF28) were located closely in the entire BM31 genome and were important for lyse or lysogeny cycle of BM31. The phage was identified as a temperate phage according to whole genome analysis and life cycle assay, with basic biological characteristics such as small burst size, short latency period, and narrow host range, consistent with the characteristics of the family Siphoviridae, subcluster B14 of the Staphylococcus bacteriophage. CONCLUSIONS The present isolation and characterisation of BM31 contributes to the Staphylococcus bacteriophage database and provides a theoretical foundation for its potential applications. To the best of our knowledge, BM31 is the only shared and completely reported phage against S. arlettae in the entire public database.
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24
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Wang Z, Guo K, Liu Y, Huang C, Wu M. Dynamic impact of virome on colitis and colorectal cancer: Immunity, inflammation, prevention and treatment. Semin Cancer Biol 2022; 86:943-954. [PMID: 34656791 PMCID: PMC9008076 DOI: 10.1016/j.semcancer.2021.10.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 09/20/2021] [Accepted: 10/08/2021] [Indexed: 02/05/2023]
Abstract
The gut microbiome includes a series of microorganism genomes, such as bacteriome, virome, mycobiome, etc. The gut microbiota is critically involved in intestine immunity and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC); however, the underlying mechanism remains incompletely understood. Clarifying the relationship between microbiota and inflammation may profoundly improve our understanding of etiology, disease progression, patient management, and the development of prevention and treatment. In this review, we discuss the latest studies of the influence of enteric viruses (i.e., commensal viruses, pathogenic viruses, and bacteriophages) in the initiation, progression, and complication of colitis and colorectal cancer, and their potential for novel preventative approaches and therapeutic application. We explore the interplay between gut viruses and host immune systems for its effects on the severity of inflammatory diseases and cancer, including both direct and indirect interactions between enteric viruses with other microbes and microbial products. Furthermore, the underlying mechanisms of the virome's roles in gut inflammatory response have been explained to infer potential therapeutic targets with examples in specific clinical trials. Given that very limited literature has thus far discussed these various topics with the gut virome, we believe these extensive analyses may provide insight into the understanding of the molecular pathogenesis of IBD and CRC, which could help add the design of improved therapies for these important human diseases.
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Affiliation(s)
- Zhihan Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58202, USA
| | - Kai Guo
- Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Yingying Liu
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58202, USA
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
| | - Min Wu
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58202, USA.
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25
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Boix-Amorós A, Monaco H, Sambataro E, Clemente JC. Novel technologies to characterize and engineer the microbiome in inflammatory bowel disease. Gut Microbes 2022; 14:2107866. [PMID: 36104776 PMCID: PMC9481095 DOI: 10.1080/19490976.2022.2107866] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, mycobiome and virome data, co-occurrence networks, and compositional data analysis. In addition, we review novel techniques to therapeutically manipulate the microbiome in IBD. We discuss the benefits and drawbacks of these technologies to increase awareness of specific biases, and to facilitate a more rigorous interpretation of results and their potential clinical application. Finally, we present future lines of research to better characterize the relation between microbial communities and IBD pathogenesis and progression.
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Affiliation(s)
- Alba Boix-Amorós
- Department of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai. New York, NY, USA
| | - Hilary Monaco
- Department of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai. New York, NY, USA
| | - Elisa Sambataro
- Department of Biological Sciences, CUNY Hunter College, New York, NY, USA
| | - Jose C. Clemente
- Department of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai. New York, NY, USA,CONTACT Jose C. Clemente Department of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai. New York, NY10029USA
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26
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Yamashina T, Shimatani M, Takeo M, Sasaki K, Orino M, Saito N, Matsumoto H, Kasai T, Kano M, Horitani S, Sumimoto K, Mitsuyama T, Yuba T, Seki T, Naganuma M. Viral Infection in Esophageal, Gastric, and Colorectal Cancer. Healthcare (Basel) 2022; 10:healthcare10091626. [PMID: 36141238 PMCID: PMC9498567 DOI: 10.3390/healthcare10091626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/09/2022] [Accepted: 08/24/2022] [Indexed: 11/18/2022] Open
Abstract
The human gastrointestinal tract, which constitutes the digestive system, contains a large number of virus particles that maintain organizational homeostasis and health. Conversely, viral pathogens have also attracted attention for their involvement in the pathogenesis of certain cancers, including gastrointestinal cancers. To aid prevention and treatment of these cancers, the relevance of gastrointestinal viral factors as potential risk factors needs to be carefully investigated. This review summarizes and discusses the available literature on the relationship between the development of esophageal, gastric, and colorectal cancers and their corresponding viruses. This review reveals that research on the association between colorectal cancer and viruses, in particular, is still in its infancy compared to the association between HPV and esophageal cancer and between EBV and gastric cancer.
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Affiliation(s)
- Takeshi Yamashina
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Masaaki Shimatani
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
- Correspondence: ; Tel.: +81-6-6992-1001; Fax: +81-6-6993-9677
| | - Masahiro Takeo
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Kotaro Sasaki
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Masahiro Orino
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Natsuko Saito
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Hironao Matsumoto
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Takeshi Kasai
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Masataka Kano
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Shunsuke Horitani
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Kimi Sumimoto
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Toshiyuki Mitsuyama
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Takafumi Yuba
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Toshihito Seki
- Division of Liver Disease Center, Kansai Medical University Medical Center, Moriguchi 570-8507, Osaka, Japan
| | - Makoto Naganuma
- The Third Department of Internal Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan
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27
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Fernandes D, Andreyev J. The Role of the Human Gut Microbiome in Inflammatory Bowel Disease and Radiation Enteropathy. Microorganisms 2022; 10:1613. [PMID: 36014031 PMCID: PMC9415405 DOI: 10.3390/microorganisms10081613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/04/2022] [Accepted: 08/08/2022] [Indexed: 12/04/2022] Open
Abstract
The human gut microbiome plays a key role in regulating host physiology. In a stable state, both the microbiota and the gut work synergistically. The overall homeostasis of the intestinal flora can be affected by multiple factors, including disease states and the treatments given for those diseases. In this review, we examine the relatively well-characterised abnormalities that develop in the microbiome in idiopathic inflammatory bowel disease, and compare and contrast them to those that are found in radiation enteropathy. We discuss how these changes may exert their effects at a molecular level, and the possible role of manipulating the microbiome through the use of a variety of therapies to reduce the severity of the underlying condition.
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Affiliation(s)
- Darren Fernandes
- The Department of Gastroenterology, United Lincolnshire NHS Trust, Lincoln County Hospital, Lincoln LN2 5QY, UK
| | - Jervoise Andreyev
- The Department of Gastroenterology, United Lincolnshire NHS Trust, Lincoln County Hospital, Lincoln LN2 5QY, UK
- The Biomedical Research Centre, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
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28
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Liang G, Gao H, Bushman FD. The pediatric virome in health and disease. Cell Host Microbe 2022; 30:639-649. [PMID: 35550667 DOI: 10.1016/j.chom.2022.04.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/22/2022] [Accepted: 04/11/2022] [Indexed: 11/03/2022]
Abstract
Associations between the global microbiome and diseases of children have been studied extensively; however, research on the viral component of the microbiome, the "virome," is less advanced. The analysis of disease associations with the virome is often technically challenging, requiring a close examination of the "virome dark matter." The gut is a particularly rich source of viral particles, and now multiple studies have reported intriguing associations of the virome with childhood diseases. For example, virome studies have elucidated new lineages of gut viruses that appear to be tightly associated with childhood diarrhea, and consistent patterns are starting to emerge from virome studies in pediatric IBD. In this review, we summarize the methods for studying the virome and recent research on the nature of the virome during childhood, focusing on specific studies of the intestinal virome in pediatric diseases.
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Affiliation(s)
- Guanxiang Liang
- Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
| | - Hongyan Gao
- Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
| | - Frederic D Bushman
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076, USA.
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29
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El Mouzan M, Assiri A, Al Sarkhy A, Alasmi M, Saeed A, Al-Hussaini A, AlSaleem B, Al Mofarreh M. Viral dysbiosis in children with new-onset celiac disease. PLoS One 2022; 17:e0262108. [PMID: 35030192 PMCID: PMC8759644 DOI: 10.1371/journal.pone.0262108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 12/16/2021] [Indexed: 01/01/2023] Open
Abstract
Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.
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Affiliation(s)
- Mohammad El Mouzan
- Department of Pediatrics (Gastroenterology), King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
- * E-mail: ,
| | - Asaad Assiri
- Department of Pediatrics (Gastroenterology), King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, Prince Abdullah Bin Khalid Celiac Disease Research Chair, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Ahmed Al Sarkhy
- Department of Pediatrics (Gastroenterology), King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Mona Alasmi
- Department of Pediatrics (Gastroenterology), King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Anjum Saeed
- Department of Pediatrics (Gastroenterology), King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Abdulrahman Al-Hussaini
- Division of Pediatric Gastroenterology, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
- Faculty of Medicine, AlFaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Badr AlSaleem
- Division of Gastroenterology, The Children Hospital, King Fahad Medical City, Pediatric Intestinal Failure and Parenteral Nutrition Program, Riyadh, Kingdom of Saudi Arabia
| | - Mohammad Al Mofarreh
- Department of Gastroenterology, Al Mofarreh PolyClinic, Riyadh, Kingdom of Saudi Arabia
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30
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Duan Y, Young R, Schnabl B. Bacteriophages and their potential for treatment of gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 2022; 19:135-144. [PMID: 34782783 PMCID: PMC8966578 DOI: 10.1038/s41575-021-00536-z] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/04/2021] [Indexed: 02/08/2023]
Abstract
Although bacteriophages have been overshadowed as therapeutic agents by antibiotics for decades, the emergence of multidrug-resistant bacteria and a better understanding of the role of the gut microbiota in human health and disease have brought them back into focus. In this Perspective, we briefly introduce basic phage biology and summarize recent discoveries about phages in relation to their role in the gut microbiota and gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease. In addition, we review preclinical studies and clinical trials of phage therapy for enteric disease and explore current challenges and potential future directions.
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Affiliation(s)
- Yi Duan
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA
| | - Ry Young
- Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA
- Center for Phage Technology, Texas A&M AgriLife Research and Texas A&M University, College Station, TX, USA
- Center for Innovative Phage Applications and Therapeutics, University of California San Diego, La Jolla, CA, USA
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA.
- Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
- Center for Innovative Phage Applications and Therapeutics, University of California San Diego, La Jolla, CA, USA.
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31
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Kumar S, Kumar A. Microbial pathogenesis in inflammatory bowel diseases. Microb Pathog 2022; 163:105383. [PMID: 34974120 DOI: 10.1016/j.micpath.2021.105383] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 12/20/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal system. Previously, it is considered the disease of the western world but now the incidence and prevalence of IBD are increasing globally with urbanization and modernization. Additionally, the major problem is the highest incidence of IBD among children and adolescents. The precise etiology of IBD is unknown and there is no cure for IBD, which is also the reason for increasing the number of cases worldwide. The IBD is a complex interplay of environment, immune system, and microbiota in a genetically susceptible host. Among these factors, the alteration in intestinal microbiota has been detected in IBD patients. The bacterial species associated with IBD include Mycobacterium paratuberculosis, adherent-invasive E. coli (AIEC), Helicobacter pylori, and Campylobacter concisus. Moreover, the efficacy of antibiotics and probiotics further suggests the role of microbes in IBD. However, no study confirmed the bacterial species as a cause of IBD as per Koch's postulates. Thus, still controversies exist regarding the role of microbes in IBD. Therefore, this paper aims to review the current literature to evaluate the role of microbes in IBD that would be a useful inventory of researchers working in this area.
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Affiliation(s)
- Sunil Kumar
- Faculty of Biosciences, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh, India.
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India.
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32
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Guzzo GL, Andrews JM, Weyrich LS. The Neglected Gut Microbiome: Fungi, Protozoa, and Bacteriophages in Inflammatory Bowel Disease. Inflamm Bowel Dis 2022; 28:1112-1122. [PMID: 35092426 PMCID: PMC9247841 DOI: 10.1093/ibd/izab343] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Indexed: 12/14/2022]
Abstract
The gut microbiome has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Studies suggest that the IBD gut microbiome is less diverse than that of the unaffected population, a phenomenon often referred to as dysbiosis. However, these studies have heavily focused on bacteria, while other intestinal microorganisms-fungi, protozoa, and bacteriophages-have been neglected. Of the nonbacterial microbes that have been studied in relation to IBD, most are thought to be pathogens, although there is evidence that some of these species may instead be harmless commensals. In this review, we discuss the nonbacterial gut microbiome of IBD, highlighting the current biases, limitations, and outstanding questions that can be addressed with high-throughput DNA sequencing methods. Further, we highlight the importance of studying nonbacterial microorganisms alongside bacteria for a comprehensive view of the whole IBD biome and to provide a more precise definition of dysbiosis in patients. With the rise in popularity of microbiome-altering therapies for the treatment of IBD, such as fecal microbiota transplantation, it is important that we address these knowledge gaps to ensure safe and effective treatment of patients.
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Affiliation(s)
- Gina L Guzzo
- Address correspondence to: Gina L. Guzzo, The University of Adelaide, Adelaide, South Australia, Australia ()
| | - Jane M Andrews
- Inflammatory Bowel Disease Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Laura S Weyrich
- School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia,Department of Anthropology and Huck Institutes of the Life Sciences, Pennsylvania State University, State College, PA, USA
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33
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Bai GH, Lin SC, Hsu YH, Chen SY. The Human Virome: Viral Metagenomics, Relations with Human Diseases, and Therapeutic Applications. Viruses 2022; 14:278. [PMID: 35215871 PMCID: PMC8876576 DOI: 10.3390/v14020278] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/20/2022] [Accepted: 01/25/2022] [Indexed: 02/07/2023] Open
Abstract
The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
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Affiliation(s)
- Geng-Hao Bai
- School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan;
- Department of Education, Taipei Medical University Hospital, Taipei City 11031, Taiwan
| | - Sheng-Chieh Lin
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan;
- Department of Pediatrics, Division of Allergy, Asthma and Immunology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Yi-Hsiang Hsu
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Shih-Yen Chen
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan;
- Department of Pediatrics, Division of Pediatric Gastroenterology and Hepatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
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An Update of Research Animal Models of Inflammatory Bowel Disease. ScientificWorldJournal 2021; 2021:7479540. [PMID: 34938152 PMCID: PMC8687830 DOI: 10.1155/2021/7479540] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 11/28/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a group of chronic disorders that includes two main disease forms, Crohn's disease, and ulcerative colitis. The understanding of the intestinal inflammation occurring in IBD has been immeasurably advanced by the development of the now numerous murine models of intestinal inflammation. The usefulness of this research tool in IBD arises from a convergence of underlying genetic susceptibility, immune system dysfunction, environmental factors, and shifts in gut microbiota. Due to the multifactorial feature of these diseases, different animal models have been used to investigate the underlying mechanisms and develop potential therapeutic strategies. The results of preclinical efficacy studies often inform the progression of therapeutic strategies. This review describes the distinct feature and limitations of each murine IBD model and discusses the previous and current lessons from the IBD models.
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Qv L, Mao S, Li Y, Zhang J, Li L. Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease. Front Cell Infect Microbiol 2021; 11:755650. [PMID: 34900751 PMCID: PMC8656360 DOI: 10.3389/fcimb.2021.755650] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are chronic, relapsing intestinal inflammatory disorders. Although the molecular mechanisms governing the pathogenesis of IBD are not completely clear, the main factors are presumed to be a complex interaction between genetic predisposition, host immune response and environmental exposure, especially the intestinal microbiome. Currently, most studies have focused on the role of gut bacteria in the onset and development of IBD, whereas little attention has been paid to the enteroviruses. Among of them, viruses that infect prokaryotes, called bacteriophages (phages) occupy the majority (90%) in population. Moreover, several recent studies have reported the capability of regulating the bacterial population in the gut, and the direct and indirect influence on host immune response. The present review highlights the roles of gut phages in IBD pathogenesis and explores the potentiality of phages as a therapeutic target for IBD treatment.
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Affiliation(s)
- Lingling Qv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Sunbing Mao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yongjun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jia Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Marongiu L, Landry JJM, Rausch T, Abba ML, Delecluse S, Delecluse H, Allgayer H. Metagenomic analysis of primary colorectal carcinomas and their metastases identifies potential microbial risk factors. Mol Oncol 2021; 15:3363-3384. [PMID: 34328665 PMCID: PMC8637581 DOI: 10.1002/1878-0261.13070] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/09/2021] [Accepted: 07/29/2021] [Indexed: 12/18/2022] Open
Abstract
The paucity of microbiome studies at intestinal tissues has contributed to a yet limited understanding of potential viral and bacterial cofactors of colorectal cancer (CRC) carcinogenesis or progression. We analysed whole-genome sequences of CRC primary tumours, their corresponding metastases and matched normal tissue for sequences of viral, phage and bacterial species. Bacteriome analysis showed Fusobacterium nucleatum, Streptococcus sanguinis, F. Hwasookii, Anaerococcus mediterraneensis and further species enriched in primary CRCs. The primary CRC of one patient was enriched for F. alocis, S. anginosus, Parvimonas micra and Gemella sp. 948. Enrichment of Escherichia coli strains IAI1, SE11, K-12 and M8 was observed in metastases together with coliphages enterobacteria phage φ80 and Escherichia phage VT2φ_272. Virome analysis showed that phages were the most preponderant viral species (46%), the main families being Myoviridae, Siphoviridae and Podoviridae. Primary CRCs were enriched for bacteriophages, showing five phages (Enterobacteria, Bacillus, Proteus, Streptococcus phages) together with their pathogenic hosts in contrast to normal tissues. The most frequently detected, and Blast-confirmed, viruses included human endogenous retrovirus K113, human herpesviruses 7 and 6B, Megavirus chilensis, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), with one patient showing EBV enrichment in primary tumour and metastases. EBV was PCR-validated in 80 pairs of CRC primary tumour and their corresponding normal tissues; in 21 of these pairs (26.3%), it was detectable in primary tumours only. The number of viral species was increased and bacterial species decreased in CRCs compared with normal tissues, and we could discriminate primary CRCs from metastases and normal tissues by applying the Hutcheson t-test on the Shannon indices based on viral and bacterial species. Taken together, our results descriptively support hypotheses on microorganisms as potential (co)risk factors of CRC and extend putative suggestions on critical microbiome species in CRC metastasis.
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Affiliation(s)
- Luigi Marongiu
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
| | | | - Tobias Rausch
- Genomics Core FacilityEuropean Molecular Biology Laboratory (EMBL)HeidelbergGermany
| | - Mohammed L. Abba
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
| | | | | | - Heike Allgayer
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
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37
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Liang G, Cobián-Güemes AG, Albenberg L, Bushman F. The gut virome in inflammatory bowel diseases. Curr Opin Virol 2021; 51:190-198. [PMID: 34763180 DOI: 10.1016/j.coviro.2021.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/05/2021] [Accepted: 10/12/2021] [Indexed: 02/06/2023]
Abstract
Dysbiosis of the microbiome has been extensively studied in inflammatory bowel diseases (IBD). The roles of bacteria and fungi have been studied in detail, but viral communities, an important component of the microbiome, have been less thoroughly investigated. Metagenomics provided a way to fill this gap by using DNA sequencing to enumerate all viruses in a sample, termed the 'virome'. Such methods have now been employed in several studies to assess associations between viral communities and IBD, yielding several commonly seen properties, including an increase in tailed bacteriophage (Caudovirales) and a decrease in the spherical Microviridae. Numerous studies of single human viruses have been carried out, but no one virus has emerged as tightly associated, focusing attention on whole virome communities and further factors. This review provides an overview of research on the human virome in IBD, with emphasis on (1) dynamics of the gut virome, (2) candidate mechanisms of virome alterations with disease, (3) methods for studying the virome, and (4) potentially actionable implications of virome data.
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Affiliation(s)
- Guanxiang Liang
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA.
| | - Ana Georgina Cobián-Güemes
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, 19104-4399, USA
| | - Frederic Bushman
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA.
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38
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Sultan S, El-Mowafy M, Elgaml A, Ahmed TAE, Hassan H, Mottawea W. Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease. Front Physiol 2021; 12:715506. [PMID: 34646151 PMCID: PMC8502967 DOI: 10.3389/fphys.2021.715506] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/18/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasive E. coli and H2S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.
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Affiliation(s)
- Salma Sultan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Mohammed El-Mowafy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Abdelaziz Elgaml
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.,Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| | - Tamer A E Ahmed
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Hebatoallah Hassan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
| | - Walid Mottawea
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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39
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Wah-Suárez MI, Vázquez MAM, Bosques-Padilla FJ. Inflammatory bowel disease: The role of commensal microbiome in immune regulation. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:626-636. [PMID: 34543718 DOI: 10.1016/j.gastrohep.2021.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/29/2021] [Indexed: 11/29/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.
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40
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Podlacha M, Grabowski Ł, Kosznik-Kawśnicka K, Zdrojewska K, Stasiłojć M, Węgrzyn G, Węgrzyn A. Interactions of Bacteriophages with Animal and Human Organisms-Safety Issues in the Light of Phage Therapy. Int J Mol Sci 2021; 22:8937. [PMID: 34445641 PMCID: PMC8396182 DOI: 10.3390/ijms22168937] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/12/2021] [Accepted: 08/17/2021] [Indexed: 12/13/2022] Open
Abstract
Bacteriophages are viruses infecting bacterial cells. Since there is a lack of specific receptors for bacteriophages on eukaryotic cells, these viruses were for a long time considered to be neutral to animals and humans. However, studies of recent years provided clear evidence that bacteriophages can interact with eukaryotic cells, significantly influencing the functions of tissues, organs, and systems of mammals, including humans. In this review article, we summarize and discuss recent discoveries in the field of interactions of phages with animal and human organisms. Possibilities of penetration of bacteriophages into eukaryotic cells, tissues, and organs are discussed, and evidence of the effects of phages on functions of the immune system, respiratory system, central nervous system, gastrointestinal system, urinary tract, and reproductive system are presented and discussed. Modulations of cancer cells by bacteriophages are indicated. Direct and indirect effects of virulent and temperate phages are discussed. We conclude that interactions of bacteriophages with animal and human organisms are robust, and they must be taken under consideration when using these viruses in medicine, especially in phage therapy, and in biotechnological applications.
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Affiliation(s)
- Magdalena Podlacha
- Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland; (M.P.); (K.Z.); (M.S.); (G.W.)
| | - Łukasz Grabowski
- Laboratory of Phage Therapy, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kładki 24, 80-822 Gdansk, Poland; (Ł.G.); (K.K.-K.)
| | - Katarzyna Kosznik-Kawśnicka
- Laboratory of Phage Therapy, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kładki 24, 80-822 Gdansk, Poland; (Ł.G.); (K.K.-K.)
| | - Karolina Zdrojewska
- Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland; (M.P.); (K.Z.); (M.S.); (G.W.)
| | - Małgorzata Stasiłojć
- Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland; (M.P.); (K.Z.); (M.S.); (G.W.)
| | - Grzegorz Węgrzyn
- Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland; (M.P.); (K.Z.); (M.S.); (G.W.)
| | - Alicja Węgrzyn
- Laboratory of Phage Therapy, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kładki 24, 80-822 Gdansk, Poland; (Ł.G.); (K.K.-K.)
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41
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El-Sayed A, Aleya L, Kamel M. Microbiota's role in health and diseases. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:36967-36983. [PMID: 34043164 PMCID: PMC8155182 DOI: 10.1007/s11356-021-14593-z] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 05/24/2021] [Indexed: 05/06/2023]
Abstract
The microbiome is a term that usually refers to the community of various microorganisms that inhabit/live inside human/animal bodies or on their skin. It forms a complex ecosystem that includes trillions of commensals, symbiotics, and even pathogenic microorganisms. The external environment, diet, and lifestyle are the major determinants influencing the microbiome's composition and vitality. Recent studies have indicated the tremendous influence of the microbiome on health and disease. Their number, constitution, variation, and viability are dynamic. All these elements are responsible for the induction, development, and treatment of many health disorders. Serious diseases such as cancer, metabolic disorders, cardiovascular diseases, and even psychological disorders such as schizophrenia are influenced directly or indirectly by microbiota. In addition, in the last few weeks, accumulating data about the link between COVID-19 and the microbiota were published. In the present work, the role of the microbiome in health and disease is discussed. A deep understanding of the exact role of microbiota in disease induction enables the prevention of diseases and the development of new therapeutic concepts for most diseases through the correction of diet and lifestyle. The present review brings together evidence from the most recent works and discusses suggested nutraceutical approaches for the management of COVID-19 pandemic.
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Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
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42
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Shen Q, Huang Z, Yao J, Jin Y. Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease. J Adv Res 2021; 37:221-233. [PMID: 35499059 PMCID: PMC9039646 DOI: 10.1016/j.jare.2021.07.002] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 07/01/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
EVs derived from different sources play modulatory functions in the intestine, especially interaction associated with microbiota. An EV-mediated interaction system was established to describe the possible mechanism of IBD pathogenesis and its cure. EVs-based treatments show great potential of clinical applications in IBD diagnosis and therapy. Background The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell–cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies. Aim of Review Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure. Key Scientific Concepts of Review EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.
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Affiliation(s)
- Qichen Shen
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Zhuizui Huang
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Jiachen Yao
- Faculty of Technology, University of Turku, Turku 20014, Finland
| | - Yuanxiang Jin
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
- Corresponding author at: 18, Chaowang Road, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
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43
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Glickman C, Hendrix J, Strong M. Simulation study and comparative evaluation of viral contiguous sequence identification tools. BMC Bioinformatics 2021; 22:329. [PMID: 34130621 PMCID: PMC8207588 DOI: 10.1186/s12859-021-04242-0] [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: 03/01/2021] [Accepted: 06/04/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Viruses, including bacteriophages, are important components of environmental and human associated microbial communities. Viruses can act as extracellular reservoirs of bacterial genes, can mediate microbiome dynamics, and can influence the virulence of clinical pathogens. Various targeted metagenomic analysis techniques detect viral sequences, but these methods often exclude large and genome integrated viruses. In this study, we evaluate and compare the ability of nine state-of-the-art bioinformatic tools, including Vibrant, VirSorter, VirSorter2, VirFinder, DeepVirFinder, MetaPhinder, Kraken 2, Phybrid, and a BLAST search using identified proteins from the Earth Virome Pipeline to identify viral contiguous sequences (contigs) across simulated metagenomes with different read distributions, taxonomic compositions, and complexities. RESULTS Of the tools tested in this study, VirSorter achieved the best F1 score while Vibrant had the highest average F1 score at predicting integrated prophages. Though less balanced in its precision and recall, Kraken2 had the highest average precision by a substantial margin. We introduced the machine learning tool, Phybrid, which demonstrated an improvement in average F1 score over tools such as MetaPhinder. The tool utilizes machine learning with both gene content and nucleotide features. The addition of nucleotide features improves the precision and recall compared to the gene content features alone.Viral identification by all tools was not impacted by underlying read distribution but did improve with contig length. Tool performance was inversely related to taxonomic complexity and varied by the phage host. For instance, Rhizobium and Enterococcus phages were identified consistently by the tools; whereas, Neisseria prophage sequences were commonly missed in this study. CONCLUSION This study benchmarked the performance of nine state-of-the-art bioinformatic tools to identify viral contigs across different simulation conditions. This study explored the ability of the tools to identify integrated prophage elements traditionally excluded from targeted sequencing approaches. Our comprehensive analysis of viral identification tools to assess their performance in a variety of situations provides valuable insights to viral researchers looking to mine viral elements from publicly available metagenomic data.
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Affiliation(s)
- Cody Glickman
- Center for Genes, Environment, and Health, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
- Computational Bioscience, University of Colorado Anschutz, 12801 E 17th Avenue, Aurora, CO, 80045, USA.
| | - Jo Hendrix
- Center for Genes, Environment, and Health, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA
- Computational Bioscience, University of Colorado Anschutz, 12801 E 17th Avenue, Aurora, CO, 80045, USA
| | - Michael Strong
- Center for Genes, Environment, and Health, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA
- Computational Bioscience, University of Colorado Anschutz, 12801 E 17th Avenue, Aurora, CO, 80045, USA
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Townsend EM, Kelly L, Muscatt G, Box JD, Hargraves N, Lilley D, Jameson E. The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome. Front Cell Infect Microbiol 2021; 11:643214. [PMID: 34150671 PMCID: PMC8213399 DOI: 10.3389/fcimb.2021.643214] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 05/19/2021] [Indexed: 12/14/2022] Open
Abstract
The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.
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Affiliation(s)
- Eleanor M Townsend
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Lucy Kelly
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - George Muscatt
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Joshua D Box
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Nicole Hargraves
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
| | - Daniel Lilley
- Warwick Medical School, The University of Warwick, Coventry, United Kingdom
| | - Eleanor Jameson
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
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45
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The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases. Microorganisms 2021; 9:microorganisms9040697. [PMID: 33801755 PMCID: PMC8066304 DOI: 10.3390/microorganisms9040697] [Citation(s) in RCA: 175] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.
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46
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Zhao W, Ren Z, Luo Y, Cheng J, Wang J, Wang Y, Yang Z, Yao X, Zhong Z, Yang W, Wu X. Metagenomics analysis of the gut microbiome in healthy and bacterial pneumonia forest musk deer. Genes Genomics 2021; 43:43-53. [PMID: 33428153 DOI: 10.1007/s13258-020-01029-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/14/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The forest musk deer (FMD, Moschus berezovskii) is an threatened species in China. Bacterial pneumonia was found to seriously restrict the development of FMD captive breeding. Historical evidence has demonstrated the relationship between immune system and intestinal Lactobacillus in FMD. OBJECTIVE We sought to elucidate the differences in the gut microbiota of healthy and bacterial pneumonia FMD. METHODS The bacterial pneumonia FMD was demonstrated by bacterial and pathological diagnosis, and the gut microbiome of healthy and bacterial pneumonia FMD was sequenced and analysed. RESULTS There are three pathogens (Pseudomonas aeruginosa, Streptococcus equinus and Trueperella pyogenes) isolated from the bacterial pneumonia FMD individuals. Compared with the healthy group, the abundance of Firmicutes and Proteobacteria in the pneumonia group was changed, and a high level of Proteobacteria was found in the pneumonia group. In addition, a higher abundance of Acinetobacter (p = 0.01) was observed in the population of the pneumonia group compared with the healthy group. Several potentially harmful bacteria and disease-related KEGG subsystems were only found in the gut of the bacterial pneumonia group. Analysis of KEGG revealed that many genes related to type IV secretion system, type IV pilus, lipopolysaccharide export system, HTH-type transcriptional regulator/antitoxin MqsA, and ArsR family transcriptional regulator were significantly enriched in the metagenome of the bacterial pneumonia FMD. CONCLUSION Our results demonstrated that the gut microbiome was significantly altered in the bacterial pneumonia group. Overall, our research improves the understanding of the potential role of the gut microbiota in the FMD bacterial pneumonia.
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Affiliation(s)
- Wei Zhao
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Ziwei Ren
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Yan Luo
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China.
| | - Jianguo Cheng
- Sichuan Institute of Musk Deer Breeding, Chengdu, 610000, Sichuan, People's Republic of China
| | - Jie Wang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Yin Wang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Zexiao Yang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Xueping Yao
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Zhijun Zhong
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Wei Yang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
| | - Xi Wu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 610000, Sichuan, People's Republic of China
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47
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Yan A, Butcher J, Mack D, Stintzi A. Virome Sequencing of the Human Intestinal Mucosal-Luminal Interface. Front Cell Infect Microbiol 2020; 10:582187. [PMID: 33194818 PMCID: PMC7642909 DOI: 10.3389/fcimb.2020.582187] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 09/14/2020] [Indexed: 01/12/2023] Open
Abstract
While the human gut virome has been increasingly explored in recent years, nearly all studies have been limited to fecal sampling. The mucosal-luminal interface has been established as a viable sample type for profiling the microbial biogeography of the gastrointestinal tract. We have developed a protocol to extract nucleic acids from viruses at the mucosal-luminal interface of the proximal and distal colon. Colonic viromes from pediatric patients with Crohn's disease demonstrated high interpatient diversity and low but significant intrapatient variation between sites. Whole metagenomics was also performed to explore virome-bacteriome interactions and to compare the viral communities observed in virome and whole metagenomic sequencing. A site-specific study of the human gut virome is a necessary step to advance our understanding of virome-bacteriome-host interactions in human diseases.
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Affiliation(s)
- Austin Yan
- Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada
| | - James Butcher
- Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada
| | - David Mack
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.,Inflammatory Bowel Disease Centre and CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
| | - Alain Stintzi
- Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada
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48
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Miller-Ensminger T, Garretto A, Stark N, Putonti C. Mimicking prophage induction in the body: induction in the lab with pH gradients. PeerJ 2020; 8:e9718. [PMID: 32944418 PMCID: PMC7469935 DOI: 10.7717/peerj.9718] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 07/23/2020] [Indexed: 12/19/2022] Open
Abstract
The majority of bacteria within the human body are lysogens, often harboring multiple bacteriophage sequences (prophages) within their genomes. While several different types of environmental stresses can trigger or induce prophages to enter into the lytic cycle, they have yet to be fully explored and understood in the human microbiota. In the laboratory, the most common induction method is the DNA damaging chemical Mitomycin C. Although pH has been listed in the literature as an induction method, it is not widely used. Here, we detail a protocol for prophage induction by culture under different pH conditions. We explored the effects of pH on prophage induction in bacterial isolates from the bladder, where the pH is well documented to vary significantly between individuals as well as between healthy individuals and individuals with urinary tract symptoms or disease. Using this protocol, we successfully induced phages from seven bladder E. coli strains. Testing conditions and stressors appropriate to the environment from which a lysogen is isolated may provide insight into community dynamics of the human microbiota.
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Affiliation(s)
| | - Andrea Garretto
- Bioinformatics Program, Loyola University of Chicago, Chicago, IL, United States of America.,Department of Microbiology & Immunology, University of Michigan-Ann Arbor, Ann Arbor, MI, United States of America
| | - Nicole Stark
- Department of Biology, Loyola University of Chicago, Chicago, IL, United States of America.,Department of Biology, Indiana University at Bloomington, Bloomington, IN, United States of America
| | - Catherine Putonti
- Bioinformatics Program, Loyola University of Chicago, Chicago, IL, United States of America.,Department of Biology, Loyola University of Chicago, Chicago, IL, United States of America.,Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL, United States of America
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49
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Raftery AL, Tsantikos E, Harris NL, Hibbs ML. Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease. Front Immunol 2020; 11:2144. [PMID: 33042125 PMCID: PMC7517908 DOI: 10.3389/fimmu.2020.02144] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 08/07/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.
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Affiliation(s)
- April L Raftery
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Evelyn Tsantikos
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Nicola L Harris
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Margaret L Hibbs
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
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50
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Happel AU, Varsani A, Balle C, Passmore JA, Jaspan H. The Vaginal Virome-Balancing Female Genital Tract Bacteriome, Mucosal Immunity, and Sexual and Reproductive Health Outcomes? Viruses 2020; 12:E832. [PMID: 32751611 PMCID: PMC7472209 DOI: 10.3390/v12080832] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/22/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022] Open
Abstract
Besides bacteria, fungi, protists and archaea, the vaginal ecosystem also contains a range of prokaryote- and eukaryote-infecting viruses, which are collectively referred to as the "virome". Despite its well-described role in the gut and other environmental niches, the vaginal virome remains understudied. With a focus on sexual and reproductive health, we summarize the currently known components of the vaginal virome, its relationship with other constituents of the vaginal microbiota and its association with adverse health outcomes. While a range of eukaryote-infecting viruses has been described to be present in the female genital tract (FGT), few prokaryote-infecting viruses have been described. Literature suggests that various vaginal viruses interact with vaginal bacterial microbiota and host immunity and that any imbalance thereof may contribute to the risk of adverse reproductive health outcomes, including infertility and adverse birth outcomes. Current limitations of vaginal virome research include experimental and analytical constraints. Considering the vaginal virome may represent the missing link in our understanding of the relationship between FGT bacteria, mucosal immunity, and adverse sexual and reproductive health outcomes, future studies evaluating the vaginal microbiome and its population dynamics holistically will be important for understanding the role of the vaginal virome in balancing health and disease.
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Affiliation(s)
- Anna-Ursula Happel
- Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (C.B.); (J.-A.P.); (H.J.)
| | - Arvind Varsani
- The Biodesign Center of Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85287-5001, USA;
- Structural Biology Research Unit, Department of Integrative Biomedical Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
| | - Christina Balle
- Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (C.B.); (J.-A.P.); (H.J.)
| | - Jo-Ann Passmore
- Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (C.B.); (J.-A.P.); (H.J.)
- NRF-DST CAPRISA Centre of Excellence in HIV Prevention, 719 Umbilo Road, Congella, Durban 4013, South Africa
- National Health Laboratory Service, Anzio Road, Observatory, Cape Town 7925, South Africa
| | - Heather Jaspan
- Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (C.B.); (J.-A.P.); (H.J.)
- Department of Pediatrics and Global Health, University of Washington, 1510 San Juan Road NE, Seattle, WA 98195, USA
- Seattle Children’s Research Institute, 307 Westlake Ave N, Seattle, WA 98109, USA
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