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Liu Y, Yan D, Chen R, Zhang Y, Wang C, Qian G. Recent insights and advances in gut microbiota's influence on host antiviral immunity. Front Microbiol 2025; 16:1536778. [PMID: 40083779 PMCID: PMC11903723 DOI: 10.3389/fmicb.2025.1536778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/17/2025] [Indexed: 03/16/2025] Open
Abstract
A diverse array of microbial organisms colonizes the human body, collectively known as symbiotic microbial communities. Among the various pathogen infections that hosts encounter, viral infections represent one of the most significant public health challenges worldwide. The gut microbiota is considered an important biological barrier against viral infections and may serve as a promising target for adjuvant antiviral therapy. However, the potential impact of symbiotic microbiota on viral infection remains relatively understudied. In this review, we discuss the specific regulatory mechanisms of gut microbiota in antiviral immunity, highlighting recent advances in how gut microbiota regulate the host immune response, produce immune-related molecules, and enhance the host's defense against viruses. Finally, we also discuss the antiviral potential of oral probiotics.
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Affiliation(s)
- Ying Liu
- Health Science Center, Ningbo University, Ningbo, Zhejiang, China
| | - Danying Yan
- Department of Infectious Diseases, The First Affiliated Hospital, Ningbo University, Ningbo, Zhejiang, China
| | - Ran Chen
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yingying Zhang
- Health Science Center, Ningbo University, Ningbo, Zhejiang, China
| | - Chuwen Wang
- Department of Infectious Diseases, The First Affiliated Hospital, Ningbo University, Ningbo, Zhejiang, China
| | - Guoqing Qian
- Health Science Center, Ningbo University, Ningbo, Zhejiang, China
- Department of Infectious Diseases, The First Affiliated Hospital, Ningbo University, Ningbo, Zhejiang, China
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Xie L, Wang L, Liao Y, Yao M, Mai T, Fan R, Han Y, Zhou G. Therapeutic potential of short-chain fatty acids for acute lung injury: a systematic review and meta-analysis of preclinical animal studies. Front Nutr 2025; 11:1528200. [PMID: 39845918 PMCID: PMC11752998 DOI: 10.3389/fnut.2024.1528200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Background Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber by intestinal commensal bacteria, have demonstrated protective effects against acute lung injury (ALI) in animal models. However, the findings have shown variability across different studies. It is necessary to conduct a comprehensive evaluation of the efficacy of these treatments and their consistency. Objective This systematic review and meta-analysis aimed to explore the effects of SCFAs on ALI based on preclinical research evidence, in order to provide new treatment strategies for ALI. Methods We included studies that tested the effects of SCFAs on ALI in animal models. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search for relevant studies was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases up to February 2024. The data were extracted in accordance with the established selection criteria, and the risk of bias was evaluated for each study. Results A total of 16 articles were finally included in the meta-analysis. The results indicated that the SCFAs significantly reduced lung wet-to-dry weight (SMD = -2.75, 95% CI = -3.46 to -2.03, p < 0.00001), lung injury scores (SMD = -5.07, 95% CI = -6.25 to -3.89, p < 0.00001), myeloperoxidase (SMD = -3.37, 95% CI = -4.05 to -2.70, p < 0.00001), tumor necrosis factor-alpha (SMD = -3.31, 95% CI = -4.45 to -2.16, p < 0.00001) and malondialdehyde (SMD = -3.91, 95% CI = -5.37 to -2.44, p < 0.00001) levels in animal models of ALI. The results of the subgroup analysis indicated that the efficacy of SCFAs varies significantly with dosage and duration of treatment. Conclusion SCFAs can reduce inflammation and oxidative stress in animal models of ALI. The clinical efficacy of SCFAs for ALI deserves further in-depth research. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=584008, CRD42024584008.
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Affiliation(s)
- Liying Xie
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Linyan Wang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yongxin Liao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Miaoen Yao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tong Mai
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rongrong Fan
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yun Han
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Gengbiao Zhou
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Lian YQ, Li PF, Guo Y, Tao YL, Liu YN, Liang ZY, Zhu SF. Interaction between ischemia-reperfusion injury and intestinal microecology in organ transplantation and its therapeutic prospects. Front Immunol 2024; 15:1495394. [PMID: 39712022 PMCID: PMC11659223 DOI: 10.3389/fimmu.2024.1495394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/15/2024] [Indexed: 12/24/2024] Open
Abstract
Organ transplantation is a vital intervention for end-stage organ failure; however, ischemia-reperfusion injury is a complication of transplantation, affecting the prognosis and survival of transplant recipients. As a complex ecosystem, recent research has highlighted the role of the intestinal microecology in transplantation, revealing its significant interplay with ischemia-reperfusion injury. This review explores the interaction between ischemia-reperfusion injury and intestinal microecology, with a special focus on how ischemia-reperfusion injury affects intestinal microecology and how these microecological changes contribute to complications after organ transplantation, such as infection and rejection. Based on a comprehensive analysis of current research advances, this study proposes potential strategies to improve transplant outcomes, offering guidance for future research and clinical practice.
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Affiliation(s)
- Yong-qi Lian
- Department of Critical Care Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Peng-fei Li
- Department of Orthopaedics, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia Autonomous Region, China
| | - Yan Guo
- Pathology Department, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia Autonomous Region, China
| | - Yan-lin Tao
- Department of Surgery ICU, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Ya-nan Liu
- Department of Surgery ICU, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Zhao-yu Liang
- Department of Critical Care Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Shu-fen Zhu
- Physical Examination Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
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Swarte JC, Zhang S, Nieuwenhuis LM, Gacesa R, Knobbe TJ, De Meijer VE, Damman K, Verschuuren EAM, Gan TC, Fu J, Zhernakova A, Harmsen HJM, Blokzijl H, Bakker SJL, Björk JR, Weersma RK. Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients. Gut 2024; 73:1650-1661. [PMID: 38955400 DOI: 10.1136/gutjnl-2023-331441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 05/12/2024] [Indexed: 07/04/2024]
Abstract
OBJECTIVE Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR). DESIGN We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality. RESULTS We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality. CONCLUSION Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.
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Affiliation(s)
- J Casper Swarte
- Gastroenterology and Hepatology, University Medical Centre, Groningen, Netherlands
| | - Shuyan Zhang
- Gastroenterology and Hepatology, University Medical Centre, Groningen, Netherlands
| | | | - Ranko Gacesa
- Gastroenterology and Hepatology, University Medical Centre, Groningen, Netherlands
- Department of Genetics, University of Groningen, University Medical Center, Groningen, Netherlands
| | - Tim J Knobbe
- University Medical Centre, Groningen, Netherlands
| | | | - Kevin Damman
- University Medical Centre, Groningen, Netherlands
| | | | - Tji C Gan
- University Medical Centre, Groningen, Netherlands
| | - Jingyuan Fu
- Department of Genetics, University Medical Center, Groningen, Netherlands
- Department of Pediatrics, University Medical Center, Groningen, Netherlands
| | | | - Hermie J M Harmsen
- Medical Microbiology, University of Groningen, University Medical Center, Groningen, Netherlands
| | | | | | - Johannes R Björk
- Gastroenterology and Hepatology, University Medical Centre, Groningen, Netherlands
| | - Rinse K Weersma
- Gastroenterology and Hepatology, University Medical Centre, Groningen, Netherlands
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Kullberg RFJ, Wikki I, Haak BW, Kauko A, Galenkamp H, Peters-Sengers H, Butler JM, Havulinna AS, Palmu J, McDonald D, Benchraka C, Abdel-Aziz MI, Prins M, Maitland van der Zee AH, van den Born BJ, Jousilahti P, de Vos WM, Salomaa V, Knight R, Lahti L, Nieuwdorp M, Niiranen T, Wiersinga WJ. Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies. THE LANCET. MICROBE 2024; 5:100864. [PMID: 38909617 DOI: 10.1016/s2666-5247(24)00079-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 02/20/2024] [Accepted: 03/14/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts. METHODS In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards. FINDINGS We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities. INTERPRETATION Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections. FUNDING Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.
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Affiliation(s)
- Robert F J Kullberg
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
| | - Irina Wikki
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Bastiaan W Haak
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Anni Kauko
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Henrike Galenkamp
- Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Hessel Peters-Sengers
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Joe M Butler
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Aki S Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland, FIMM-HiLIFE, Finland
| | - Joonatan Palmu
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland; Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, San Diego, CA, USA
| | | | - Mahmoud I Abdel-Aziz
- Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | | | - Bert-Jan van den Born
- Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Internal Medicine, Division of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Willem M de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, San Diego, CA, USA
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Max Nieuwdorp
- Department of Internal Medicine, Division of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Teemu Niiranen
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland; Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - W Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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Chen Z, Chang X, Ye Q, Gao Y, Deng R. Kidney transplantation and gut microbiota. Clin Kidney J 2024; 17:sfae214. [PMID: 39170931 PMCID: PMC11336673 DOI: 10.1093/ckj/sfae214] [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: 01/11/2024] [Indexed: 08/23/2024] Open
Abstract
Kidney transplantation is an effective way to improve the condition of patients with end-stage renal disease. However, maintaining long-term graft function and improving patient survival remain a key challenge after kidney transplantation. Dysbiosis of intestinal flora has been reported to be associated with complications in renal transplant recipients. The commensal microbiota plays an important role in the immunomodulation of the transplant recipient responses. However, several processes, such as the use of perioperative antibiotics and high-dose immunosuppressants in renal transplant recipients, can lead to gut dysbiosis and disrupt the interaction between the microbiota and the host immune responses, which in turn can lead to complications such as infection and rejection in organ recipients. In this review, we summarize and discuss the changes in intestinal flora and their influencing factors in patients after renal transplantation as well as the evidence related to the impact of intestinal dysbiosis on the prognosis of renal transplantation from in vivo and clinical studies, and conclude with a discussion of the use of microbial therapy in the transplant population. Hopefully, a deeper understanding of the function and composition of the microbiota in patients after renal transplantation may assist in the development of clinical strategies to restore a normal microbiota and facilitate the clinical management of grafts in the future.
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Affiliation(s)
- Zehuan Chen
- Organ Transplantation Center, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Sun Yat-sen University First Affiliated Hospital
| | - Xinhua Chang
- Organ Transplantation Center, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Sun Yat-sen University First Affiliated Hospital
| | - Qianyu Ye
- Organ Transplantation Center, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Sun Yat-sen University First Affiliated Hospital
| | - Yifang Gao
- Organ Transplantation Center, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Sun Yat-sen University First Affiliated Hospital
| | - Ronghai Deng
- Organ Transplantation Center, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University First Affiliated Hospital
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Sun Yat-sen University First Affiliated Hospital
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Sung C, Park CG, Maienschein-Cline M, Chlipala G, Green S, Doorenbos A, Fink A, Bronas U, Lockwood M. Associations Between Gut Microbial Features and Sickness Symptoms in Kidney Transplant Recipients. Biol Res Nurs 2024; 26:368-379. [PMID: 38231673 DOI: 10.1177/10998004241227560] [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] [Indexed: 01/19/2024]
Abstract
PURPOSE The study investigated the relationship of gut microbiome features and sickness symptoms in kidney transplant recipients. METHODS Employing a prospective, longitudinal design, we collected data from 19 participants who had undergone living-donor kidney transplant at three timepoints (pre-transplant and 1 week and 3 months post-transplant). Sickness symptom data and fecal specimens were collected at each timepoint. Participants were grouped either as high or low sickness symptom severity at baseline. Shotgun metagenomics sequencing characterized gut microbial structure and functional gene content. Fecal microbial features, including alpha (evenness and richness within samples) and beta (dissimilarities between samples) diversity and relative abundances, were analyzed using R statistical packages. Cross-sectional and longitudinal analyses examined relationships between gut microbial features and sickness symptoms. RESULTS Although our exploratory findings revealed no significant differences in alpha and beta diversity between groups, the high-severity group showed lower microbial richness and evenness than the low-severity group. The high-severity group had enriched relative abundance of bacteria from the genera Citrobacter and Enterobacter and reduced relative abundance of bacteria from the genus Akkermansia across timepoints. No functional genes differed significantly between groups or timepoints. CONCLUSIONS Kidney transplant recipients with high symptom burden displayed increased putative proinflammatory bacteria and decreased beneficial bacteria. This study provides an effect size that future large cohort studies can employ to confirm associations between gut microbial features and sickness symptom experiences in the kidney transplant population. The study findings also have implications for future interventional studies aiming to alleviate the sickness symptom burden in this population.
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Affiliation(s)
- Choa Sung
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, USA
| | - Chang Gi Park
- Department of Population Health Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, USA
| | | | - George Chlipala
- Associate Director of Research Informatics Core, University of Illinois at Chicago, Chicago, IL, USA
| | - Stefan Green
- Department of Internal Medicine, Division of Infectious Disease, Rush University Medical Center, Chicago, IL, USA
| | - Ardith Doorenbos
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, USA
| | - Anne Fink
- Biobehavioral Science in Nursing and Rehabilitation & Regenerative Medicine, Columbia University, New York, NY, USA
| | - Ulf Bronas
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, USA
| | - Mark Lockwood
- Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, USA
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8
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Zhang J, Ling L, Xiang L, Li W, Bao P, Yue W. Role of the gut microbiota in complications after ischemic stroke. Front Cell Infect Microbiol 2024; 14:1334581. [PMID: 38644963 PMCID: PMC11026644 DOI: 10.3389/fcimb.2024.1334581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.
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Affiliation(s)
- Jinwei Zhang
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Ling Ling
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
| | - Lei Xiang
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
| | - Wenxia Li
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Pengnan Bao
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Wei Yue
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
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Salvadori M, Rosso G. Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation. World J Transplant 2024; 14:90194. [PMID: 38576749 PMCID: PMC10989467 DOI: 10.5500/wjt.v14.i1.90194] [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: 11/26/2023] [Revised: 12/22/2023] [Accepted: 12/29/2023] [Indexed: 03/15/2024] Open
Abstract
Gut microbiota is often modified after kidney transplantation. This principally happens in the first period after transplantation. Antibiotics and, most of all, immunosuppressive drugs are the main responsible. The relationship between immunosuppressive drugs and the gut microbiota is bilateral. From one side immunosuppressive drugs modify the gut microbiota, often generating dysbiosis; from the other side microbiota may interfere with the immunosuppressant pharmacokinetics, producing products more or less active with respect to the original drug. These phenomena have influence over the graft outcomes and clinical consequences as rejections, infections, diarrhea may be caused by the dysbiotic condition. Corticosteroids, calcineurin inhibitors such as tacrolimus and cyclosporine, mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known. In contrast is well known how the gut microbiota may interfere with glucocorticoids, which may be transformed into androgens. Tacrolimus may be transformed by micro biota into a product called M1 that is 15-fold less active with respect to tacrolimus. The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glu curonidase, may be transformed into the inactive product.
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Affiliation(s)
- Maurizio Salvadori
- Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Tuscany, Italy
| | - Giuseppina Rosso
- Division of Nephrology, San Giovanni di Dio Hospital, Florence 50143, Toscana, Italy
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10
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Elgarten CW, Margolis EB, Kelly MS. The Microbiome and Pediatric Transplantation. J Pediatric Infect Dis Soc 2024; 13:S80-S89. [PMID: 38417089 PMCID: PMC10901476 DOI: 10.1093/jpids/piad062] [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: 06/06/2023] [Accepted: 08/25/2023] [Indexed: 03/01/2024]
Abstract
The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization resistance, influences the risk of infections after transplantation, including those caused by multidrug-resistant organisms. In addition, through both direct interactions with the host immune system and via the production of metabolites that impact local and systemic immunity, the microbiome plays an important role in the establishment of immune tolerance after transplantation, and conversely, in the development of graft-versus-host disease and graft rejection. This review offers a comprehensive overview of the evidence for the role of the microbiome in hematopoietic cell and solid organ transplant complications, drivers of microbiome shift during transplantation, and the potential of microbiome-based therapies to improve pediatric transplantation outcomes.
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Affiliation(s)
- Caitlin W Elgarten
- Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Elisa B Margolis
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
- Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
| | - Matthew S Kelly
- Departments of Pediatrics and Molecular Genetics & Microbiology, Duke University School of Medicine, Durham, North Carolina, USA
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11
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Prétet JL, Touzé A, Pazart L, Boiteux G, Fournier V, Vidal C, Arnold F, Ducloux D, Lepiller Q, Mougin C. Anogenital distribution of mucosal HPV in males and females before and after renal transplantation. Infect Dis Now 2024; 54:104830. [PMID: 37949172 DOI: 10.1016/j.idnow.2023.104830] [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: 06/30/2023] [Revised: 10/18/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023]
Abstract
INTRODUCTION Immunosuppressive drugs taken by transplant recipients may favor HPV infection at anogenital sites. HPV-type prevalence was studied in males and females before and after renal transplantation. PATIENTS AND METHODS Anal, cervical and penile samples were taken from 62 patients before transplantation and from 41 patients after transplantation. HPV DNA was investigated using the INNO-LiPA HPV genotyping extra test and HPV-type distribution determined. RESULTS Before transplantation, up to 30% of analyzed samples harbored HPV DNA, with the highest prevalence found in cervical specimens (60%). After transplantation, a trend toward HPV clearance was observed in females. By contrast, a trend toward incident infections by a wide variety of HPV genotypes at the penis and anal level was documented in men. CONCLUSION High prevalence of HPV at anogenital sites was documented before and after renal transplantation. Immunosuppressive drugs taken after transplantation may impact HPV acquisition or reactivation, especially in males. Special attention should be paid in view of preventing HPV-associated diseases in this vulnerable population.
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Affiliation(s)
- Jean-Luc Prétet
- Université de Franche-Comté, Carcinogenèse associée aux HPV, F-25000, Besançon, France; CHU Besançon, Centre National de Référence Papillomavirus, F-25000, Besançon, France; CHU Besançon, CIC1431, F-25000, Besançon, France.
| | - Antoine Touzé
- UMR INRA ISP 1282, Équipe Biologie des infections à polyomavirus, Université de Tours, Tours, France
| | | | | | | | | | - Françoise Arnold
- UMR INRA ISP 1282, Équipe Biologie des infections à polyomavirus, Université de Tours, Tours, France
| | - Didier Ducloux
- Université de Franche-Comté, EFS, INSERM, inst RIGHT, F-25000, Besançon, France
| | - Quentin Lepiller
- Université de Franche-Comté, Carcinogenèse associée aux HPV, F-25000, Besançon, France; CHU Besançon, Centre National de Référence Papillomavirus, F-25000, Besançon, France
| | - Christiane Mougin
- CHU Besançon, Centre National de Référence Papillomavirus, F-25000, Besançon, France; Université de Franche-Comté, EFS, INSERM, inst RIGHT, F-25000, Besançon, France
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12
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Degraeve AL, Bindels LB, Haufroid V, Moudio S, Boland L, Delongie KA, Dewulf JP, Eddour DC, Mourad M, Elens L. Tacrolimus Pharmacokinetics is Associated with Gut Microbiota Diversity in Kidney Transplant Patients: Results from a Pilot Cross-Sectional Study. Clin Pharmacol Ther 2024; 115:104-115. [PMID: 37846607 DOI: 10.1002/cpt.3077] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/30/2023] [Indexed: 10/18/2023]
Abstract
Clinical use of tacrolimus (TAC), an essential immunosuppressant following transplantation, is complexified by its high pharmacokinetic (PK) variability. The gut microbiota gains growing interest but limited investigations have evaluated its contribution to TAC PKs. Here, we explore the associations between the gut microbiota composition and TAC PKs. In this pilot cross-sectional study (Clinicaltrial.gov NCT04360031), we recruited 93 CYP3A5 non-expressers stabilized kidney transplant recipients. Gut microbiota composition was characterized by 16S rRNA gene sequencing, TAC PK parameters were computed, and additional demographic and medical covariates were collected. Associations between PK parameters or diabetic status and the gut microbiota composition, as reflected by α- and β-diversity metrics, were evaluated. Patients with higher TAC area under the curve AUC/(dose/kg) had higher bacterial richness, and TAC PK parameters were associated with specific bacterial taxa (e.g., Bilophila) and amplicon sequence variant (ASV; e.g., ASV 1508 and ASV 1982 (Veillonella/unclassified Sporomusaceae); ASV 664 (unclassified Oscillospiraceae)). Building a multiple linear regression model showed that ASV 1508 (co-abundant with ASV 1982) and ASV 664 explained, respectively, 16.0% and 4.6% of the interindividual variability in TAC AUC/(dose/kg) in CYP3A5 non-expresser patients, when adjusting for hematocrit and age. Anaerostipes relative abundance was decreased in patients with diabetes. Altogether, this pilot study revealed unprecedented links between the gut microbiota composition and diversity and TAC PKs in stable kidney transplant recipients. It supports the relevance of studying the gut microbiota as an important contributor to TAC PK variability. Elucidating the causal relationship will offer new perspectives to predict TAC inter- and intra-PK variability.
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Affiliation(s)
- Alexandra L Degraeve
- Department of Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Laure B Bindels
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Vincent Haufroid
- Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Serge Moudio
- Department of Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Lidvine Boland
- Department of Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
- Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | | | - Joseph P Dewulf
- Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- Institute of Rare Diseases, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- Department of Biochemistry, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Djamila Chaib Eddour
- Kidney and Pancreas Transplantation Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Michel Mourad
- Kidney and Pancreas Transplantation Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Laure Elens
- Department of Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
- Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
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13
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Swarte JC, Knobbe TJ, Björk JR, Gacesa R, Nieuwenhuis LM, Zhang S, Vila AV, Kremer D, Douwes RM, Post A, Quint EE, Pol RA, Jansen BH, de Borst MH, de Meijer VE, Blokzijl H, Berger SP, Festen EAM, Zhernakova A, Fu J, Harmsen HJM, Bakker SJL, Weersma RK. Health-related quality of life is linked to the gut microbiome in kidney transplant recipients. Nat Commun 2023; 14:7968. [PMID: 38042820 PMCID: PMC10693618 DOI: 10.1038/s41467-023-43431-8] [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: 02/12/2023] [Accepted: 11/08/2023] [Indexed: 12/04/2023] Open
Abstract
Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10-65) and mental HRQoL (R = -0.14, P = 1.3 × 10-3). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R2 = 0.58%, FDR = 5.43 × 10-4 and R2 = 0.37%, FDR = 1.38 × 10-3, respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.
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Affiliation(s)
- J Casper Swarte
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Tim J Knobbe
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Johannes R Björk
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ranko Gacesa
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Lianne M Nieuwenhuis
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Shuyan Zhang
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Arnau Vich Vila
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Daan Kremer
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Rianne M Douwes
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Adrian Post
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Evelien E Quint
- Department of Surgery, division of Transplantation Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robert A Pol
- Department of Surgery, division of Transplantation Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Bernadien H Jansen
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Vincent E de Meijer
- Department of Surgery, section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stefan P Berger
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jingyuan Fu
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Hermie J M Harmsen
- Department of Medical Microbiology and Infection prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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14
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Yan P, Luo S, Guo L, Wang X, Ren X, Lv J, Chen Y, Lin X, Chen J, Wang R. Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis. Microorganisms 2023; 11:2747. [PMID: 38004758 PMCID: PMC10673061 DOI: 10.3390/microorganisms11112747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/05/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.
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Affiliation(s)
- Pengpeng Yan
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Sulin Luo
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Luying Guo
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Xingxia Wang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Department of Nephrology, 903rd Hospital of PLA, Hangzhou 310013, China
| | - Xue Ren
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Department of Nephrology, Huzhou Central Hospital, Huzhou 313000, China
| | - Junhao Lv
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Ying Chen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Xinyu Lin
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
| | - Rending Wang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; (P.Y.); (S.L.); (L.G.); (X.W.); (X.R.); (J.L.); (Y.C.); (X.L.); (J.C.)
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou 310003, China
- National Key Clinical Department of Kidney Diseases, Hangzhou 310003, China
- Institute of Nephrology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou 310003, China
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15
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Dela Cruz M, Lin H, Han J, Adler E, Boissiere J, Khalid M, Sidebottom A, Sundararajan A, Lehmann C, Moran A, Odenwald M, Stutz M, Kim G, Pinney S, Jeevanandam V, Alegre ML, Pamer E, Nguyen AB. Reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from heart allograft recipients. FRONTIERS IN TRANSPLANTATION 2023; 2:1182534. [PMID: 38993864 PMCID: PMC11235359 DOI: 10.3389/frtra.2023.1182534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 06/30/2023] [Indexed: 07/13/2024]
Abstract
Background Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients. Methods In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT. Results Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors. Conclusions Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.
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Affiliation(s)
- Mark Dela Cruz
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States
| | - Huaiying Lin
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Jiho Han
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States
| | - Emerald Adler
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Jaye Boissiere
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Maryam Khalid
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Ashley Sidebottom
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Anitha Sundararajan
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Christopher Lehmann
- Department of Medicine, Section of Infectious Diseases, University of Chicago Medicine, Chicago, IL, United States
| | - Angelica Moran
- Department of Pathology, University of Chicago Medicine, Chicago, IL, United States
| | - Matthew Odenwald
- Department of Medicine, Section of Gastroenterology, University of Chicago Medicine, Chicago, IL, United States
| | - Matthew Stutz
- Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago Medicine, Chicago, IL, United States
| | - Gene Kim
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States
| | - Sean Pinney
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States
| | - Valluvan Jeevanandam
- Department of Surgery, Section of Cardiac Surgery, University of Chicago Medicine, Chicago, IL, United States
| | - Maria-Luisa Alegre
- Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, United States
| | - Eric Pamer
- Duchossois Family Institute, University of Chicago, Chicago, IL, United States
| | - Ann B. Nguyen
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States
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16
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Ye J, Yao J, He F, Sun J, Zhao Z, Wang Y. Regulation of gut microbiota: a novel pretreatment for complications in patients who have undergone kidney transplantation. Front Cell Infect Microbiol 2023; 13:1169500. [PMID: 37346031 PMCID: PMC10280007 DOI: 10.3389/fcimb.2023.1169500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 05/23/2023] [Indexed: 06/23/2023] Open
Abstract
Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.
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Affiliation(s)
- Jiajia Ye
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junxia Yao
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangfang He
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Sun
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Zhao
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yumei Wang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Zafar H, Saier MH. Understanding the Relationship of the Human Bacteriome with COVID-19 Severity and Recovery. Cells 2023; 12:cells12091213. [PMID: 37174613 PMCID: PMC10177376 DOI: 10.3390/cells12091213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/05/2023] [Accepted: 04/11/2023] [Indexed: 05/15/2023] Open
Abstract
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. Evidence has been provided that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on its way to an endemic form; however, the threat of the virus is more for susceptible (older and immunocompromised) people. The human body has millions of bacterial cells that influence health and disease. As a consequence, the bacteriomes in the human body substantially influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. In major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. That have a positive effect on the functionality of the immune system and human health. These select bacterial spp. Could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. That could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacies.
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Affiliation(s)
- Hassan Zafar
- Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, CA 92093-0116, USA
- Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
| | - Milton H Saier
- Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, CA 92093-0116, USA
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18
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García-Martínez Y, Borriello M, Capolongo G, Ingrosso D, Perna AF. The Gut Microbiota in Kidney Transplantation: A Target for Personalized Therapy? BIOLOGY 2023; 12:biology12020163. [PMID: 36829442 PMCID: PMC9952448 DOI: 10.3390/biology12020163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/15/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023]
Abstract
Kidney transplantation improves quality of life, morbidity, and mortality of patients with kidney failure. However, integrated immunosuppressive therapy required to preserve graft function is associated with the development of post-transplant complications, including infections, altered immunosuppressive metabolism, gastrointestinal toxicity, and diarrhea. The gut microbiota has emerged as a potential therapeutic target for personalizing immunosuppressive therapy and managing post-transplant complications. This review reports current evidence on gut microbial dysbiosis in kidney transplant recipients, alterations in their gut microbiota associated with kidney transplantation outcomes, and the application of gut microbiota intervention therapies in treating post-transplant complications.
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Affiliation(s)
- Yuselys García-Martínez
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Via Pansini, Bldg 17, 80131 Naples, Italy
- Correspondence:
| | - Margherita Borriello
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy
| | - Giovanna Capolongo
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Via Pansini, Bldg 17, 80131 Naples, Italy
| | - Diego Ingrosso
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy
| | - Alessandra F. Perna
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Via Pansini, Bldg 17, 80131 Naples, Italy
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19
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Kleinová P, Beliančinová M, Vnučák M, Graňák K, Dedinská I. Gut microbiome and renal transplantation. VNITRNI LEKARSTVI 2023; 69:41-46. [PMID: 36931881 DOI: 10.36290/vnl.2023.006] [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: 06/18/2023]
Abstract
Gut microbiome research has been a surge of interest in many branches of medicine in the last decade. Our main aim is to show ability of microbes to infuence the functions of human body, especially in the immune system, and on the other hand to clarify changes in composition of gut microbiome in the post-transplantation period and their function for the long-term survival of the graft and the patient in the context of the occurrence of a wide range of complications. Kidney transplantation with the subsequent use of immunosuppressants and antibiotics affects the composition of gut microbiome. The subsequent development of dysbiosis significantly increases the risk of acute rejection, interstitial fibrosis and tubular atrophy of the graft, post-transplant diarrhoea, organ´s infections and metabolic complications such as post-transplant diabetes mellitus. Also important is the influence of the microorganisms of the gut microbiome on metabolism of immunosuppressants with the production of less effective components and the subsequent necessity of modifying their levels with a higher risk of underdosing and the occurrence of graft rejection. Support of the composition of the gut microbiome in the post-transplantation period in favor of bacteria producing short chain fatty acids (SCFA) is possible by changing of diet with predominance of fiber, the application of probiotics, prebiotics. According to available studies, it can lead to benefits in term of metabolic compensation, to the induction of donor-specific tolerance and many others, with an overall improvement in the quality of patient and graft survival.
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20
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McMullan B, Bryant PA, Duffy E, Bielicki J, De Cock P, Science M, Zembles T, Timberlake K, Monsees E, Hamdy RF, Tribble AC, Newland J, Patel S. Multinational consensus antimicrobial stewardship recommendations for children managed in hospital settings. THE LANCET. INFECTIOUS DISEASES 2022; 23:e199-e207. [PMID: 36566768 DOI: 10.1016/s1473-3099(22)00726-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/07/2022] [Accepted: 10/17/2022] [Indexed: 12/24/2022]
Abstract
Children are entitled to receive antibiotic therapy that is based on evidence and best practice, but might be overlooked in hospital programmes designed to achieve antimicrobial stewardship [AMS]. This failure to include children could be because children make up small proportion of patients in most hospitals, and are cared for by specialised paediatric staff. We reviewed the evidence and consulted experts in three global regions to develop ten recommendations for good-practice in hospital AMS programmes for children. We performed a review of scientific research, published between Jan 1, 2007, and Oct 17, 2019, concerning AMS, and formed a multinational expert group comprising members from the USA, Canada, the UK, Belgium, Switzerland, Australia, and Aotearoa New Zealand to develop the recommendations. These recommendations aim to help health-care workers who care for children in these regions to deliver best-practice care. We surveyed health-care workers with expertise in antibiotic therapy for children across these regions, and found that the recommendations were considered both very important and generally feasible. These recommendations should be implemented in hospitals to improve antibiotic therapy for children and to stimulate research into future improvements in care.
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Affiliation(s)
- Brendan McMullan
- Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; Department of Immunology, Sydney Children's Hospital Randwick, Sydney, NSW, Australia; Department of Infectious Diseases, Sydney Children's Hospital Randwick, Sydney, NSW, Australia.
| | - Penelope A Bryant
- Departments of Hospital-in-the-Home, The Royal Children's Hospital, Melbourne, VIC, Australia; Department of Infectious Diseases, The Royal Children's Hospital, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
| | - Eamon Duffy
- Departments of Infectious Disease, Te Whatu Ora Health New Zealand, Auckland, New Zealand; Department of Pharmacy, Te Whatu Ora Health New Zealand, Auckland, New Zealand; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Julia Bielicki
- Department of Paediatric Infectious Diseases and Infection Prevention and Control, University of Basel Children's Hospital, Basel, Switzerland; Centre for Neonatal and Paediatric Infection, St George's University, London, UK
| | - Pieter De Cock
- Department of Pharmacy, Ghent University Hospital, Ghent, Belgium; Department of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium; Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
| | - Michelle Science
- Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Tracy Zembles
- Department of Enterprise Safety, Children's Wisconsin, WI, Milwaukee, USA
| | - Kathryn Timberlake
- Department of Pharmacy, The Hospital for Sick Children, Toronto, ON, Canada
| | - Elizabeth Monsees
- Children's Mercy Hospital, Kansas City, MO, USA; Department of Pediatrics, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Rana F Hamdy
- Division of Infectious Diseases, Children's National Hospital, Washington DC, USA; Department of Pediatrics, George Washington School of Medicine and Health Sciences, Washington DC, USA
| | - Alison C Tribble
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Jason Newland
- Department of Infectious Diseases, Washington University School of Medicine in St Louis, St Louis, MO, USA
| | - Sanjay Patel
- Department of Paediatric Infectious Diseases and Immunology, Southampton Children's Hospital, Southampton, UK
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21
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Stutz MR, Dylla NP, Pearson SD, Lecompte-Osorio P, Nayak R, Khalid M, Adler E, Boissiere J, Lin H, Leiter W, Little J, Rose A, Moran D, Mullowney MW, Wolfe KS, Lehmann C, Odenwald M, De La Cruz M, Giurcanu M, Pohlman AS, Hall JB, Chaubard JL, Sundararajan A, Sidebottom A, Kress JP, Pamer EG, Patel BK. Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure. Nat Commun 2022; 13:6615. [PMID: 36329015 PMCID: PMC9633022 DOI: 10.1038/s41467-022-34260-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 10/18/2022] [Indexed: 11/06/2022] Open
Abstract
Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.
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Affiliation(s)
- Matthew R Stutz
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Nicholas P Dylla
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Steven D Pearson
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Paola Lecompte-Osorio
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Ravi Nayak
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Maryam Khalid
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Emerald Adler
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Jaye Boissiere
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Huaiying Lin
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - William Leiter
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Jessica Little
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Amber Rose
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - David Moran
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Michael W Mullowney
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Krysta S Wolfe
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Christopher Lehmann
- Department of Medicine, Section of Infectious Diseases & Global Health, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Matthew Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Mark De La Cruz
- Department of Medicine, Section of Cardiology, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Mihai Giurcanu
- Biological Sciences Division, Biostatistics Laboratory & Research Computing Group, University of Chicago, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Anne S Pohlman
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Jesse B Hall
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Jean-Luc Chaubard
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Anitha Sundararajan
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - Ashley Sidebottom
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA
| | - John P Kress
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA
| | - Eric G Pamer
- Duchossois Family Institute, University of Chicago, 900 E. 57th St, Chicago, IL, 60637, USA.
- Department of Medicine, Section of Infectious Diseases & Global Health, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA.
| | - Bhakti K Patel
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL, 60637, USA.
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22
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Exposure to antibiotics with anaerobic activity before respiratory viral infection is associated with respiratory disease progression after hematopoietic cell transplant. Bone Marrow Transplant 2022; 57:1765-1773. [PMID: 36064752 DOI: 10.1038/s41409-022-01790-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 11/08/2022]
Abstract
We examined associations between specific antibiotic exposures and progression to lower respiratory tract disease (LRTD) following individual respiratory viral infections (RVIs) after hematopoietic cell transplantation (HCT). We analyzed allogeneic HCT recipients of all ages with their first RVI during the first 100 days post-HCT. For the 21 days before RVI onset, we recorded any receipt of specific groups of antibiotics, and the cumulative sum of the number of antibiotics received for each day (antibiotic-days). We used Cox proportional hazards models to assess the relationship between antibiotic exposure and progression to LRTD. Among 469 patients with RVI, 124 progressed to LRTD. Compared to no antibiotics, use of antibiotics with broad anaerobic activity in the prior 21 days was associated with progression to LRTD after adjusting for age, virus type, hypoalbuminemia, neutropenia, steroid use, and monocytopenia (HR 2.2, 95% CI 1.1-4.1). Greater use of those antibiotics (≥7 antibiotic days) was also associated with LRTD in adjusted models (HR 2.2, 95% CI 1.1-4.3). Results were similar after adjusting for lymphopenia instead of monocytopenia. Antibiotic use is associated with LRTD after RVI across different viruses in HCT recipients. Prospective studies using anaerobe-sparing antibiotics should be explored to assess impact on LRTD in patients undergoing HCT.
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23
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Sharma A, Giorgakis E. Gut microbiome dysbiosis in the setting of solid organ transplantation: What we have gleaned from human and animal studies. World J Transplant 2022; 12:157-162. [PMID: 36051453 PMCID: PMC9331413 DOI: 10.5500/wjt.v12.i7.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 10/27/2021] [Accepted: 06/27/2022] [Indexed: 02/06/2023] Open
Abstract
The human gut microbiome refers to all of the microorganisms present throughout the length of the gastrointestinal tract. Gut flora influence host metabolic and immune processes in myriad ways. They also play an important role in maturation and modulation of the immune system. Dysbiosis or a pathologic alteration in gut flora has been implicated in a number of diseases ranging from metabolic, autoimmune and degenerative. Whether dysbiosis has similar implications in organ transplant has been the focus of a number of pre-clinical and clinical studies. Researchers have observed significant microbiome changes after solid organ transplantation in humans that have been associated with clinical outcomes such as post-transplant urinary tract infections and diarrhea. In this article, we will discuss the available data regarding pathologic alterations in gut microbiome (dysbiosis) in solid organ transplant recipients as well as some of challenges in this field. We will also discuss animal studies focusing on mouse models of transplantation that shed light on the underlying mechanisms that explain these findings.
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Affiliation(s)
- Aparna Sharma
- Department of Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR 72223, United States
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72223, United States
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24
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Zhang ZJ, Lehmann CJ, Cole CG, Pamer EG. Translating Microbiome Research From and To the Clinic. Annu Rev Microbiol 2022; 76:435-460. [DOI: 10.1146/annurev-micro-041020-022206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside. Expected final online publication date for the Annual Review of Microbiology, Volume 76 is September 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Zhenrun J. Zhang
- Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA
| | | | - Cody G. Cole
- Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA
- Department of Microbiology, University of Chicago, Chicago, Illinois, USA
| | - Eric G. Pamer
- Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA
- Department of Microbiology, University of Chicago, Chicago, Illinois, USA
- Department of Medicine and Pathology, University of Chicago, Chicago, Illinois, USA
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25
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Zhang J, Qin H, Chang M, Yang Y, Lin J. Gut Microbiota Dysbiosis in BK Polyomavirus-Infected Renal Transplant Recipients: A Case-Control Study. Front Cell Infect Microbiol 2022; 12:860201. [PMID: 35694540 PMCID: PMC9186314 DOI: 10.3389/fcimb.2022.860201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 04/14/2022] [Indexed: 11/17/2022] Open
Abstract
Background BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity, changes in the gut microbiota are associated with a variety of infections. However, the correlation between microbiota dysbiosis and posttransplant BK polyomavirus infection was rarely studied. Thus, this study aimed to characterize the gut microbiota in BK polyomavirus-infected renal transplant recipients in order to explore the biomarkers that might be potential therapeutic targets and establish a prediction model for posttransplant BK polyomavirus infection based on the gut microbiota. Methods We compared the gut microbial communities of 25 BK polyomavirus-infected renal transplant recipients with 23 characteristic-matched controls, applying the 16S ribosomal RNA gene amplicon sequencing technique. Results At the phylum level, Firmicutes/Bacteroidetes ratio significantly increased in the BK polyomavirus group. Bacteroidetes was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, Romboutsia and Roseburia exhibited a significant difference between the two groups. No significant difference was observed in microbial alpha diversity. Beta diversity revealed a significant difference between the two groups. Nine distinguishing bacterial taxa were discovered between the two groups. We established a random forest model using genus taxa to predict BK polyomavirus infectious status, which achieved the best accuracy (80.71%) with an area under the curve of 0.82. Two genera were included in the best model, which were Romboutsia and Actinomyces. Conclusions BK polyomavirus-infected patients had gut microbiota dysbiosis in which the Firmicutes/Bacteroidetes ratio increased in the course of the viral infection. Nine distinguishing bacterial taxa might be potential biomarkers of BK polyomavirus infection. The random forest model achieved an accuracy of 80.71% in predicting the BKV infectious status, with Romboutsia and Actinomyces included.
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Affiliation(s)
- Jian Zhang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Hao Qin
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Mingyu Chang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yang Yang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jun Lin
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
- *Correspondence: Jun Lin,
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26
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Long-distance relationships - regulation of systemic host defense against infections by the gut microbiota. Mucosal Immunol 2022; 15:809-818. [PMID: 35732817 DOI: 10.1038/s41385-022-00539-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/29/2022] [Accepted: 06/04/2022] [Indexed: 02/04/2023]
Abstract
Despite compartmentalization within the lumen of the gastrointestinal tract, the gut microbiota has a far-reaching influence on immune cell development and function throughout the body. This long-distance relationship is crucial for immune homeostasis, including effective host defense against invading pathogens that cause systemic infections. Herein, we review new insights into how commensal microbes that are spatially restricted to the gut lumen can engage in long-distance relationships with innate and adaptive immune cells at systemic sites to fortify host defenses against infections. In addition, we explore the consequences of intestinal dysbiosis on impaired host defense and immune-mediated pathology during infections, including emerging evidence linking dysbiosis with aberrant systemic inflammation and immune-mediated organ damage in sepsis. As such, therapeutic modification of the gut microbiota is an emerging target for interventions to prevent and/or treat systemic infections and sepsis by harnessing the long-distance relationships between gut microbes and systemic immunity.
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27
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Shi HY, Zhu X, Li WL, Mak JWY, Wong SH, Zhu ST, Guo SL, Chan FKL, Zhang ST, Ng SC. Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies. Eur J Nutr 2021; 60:4151-4174. [PMID: 33852069 PMCID: PMC8044287 DOI: 10.1007/s00394-021-02519-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms supporting the effect remain unclear. AIM To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs. METHODS We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated. RESULTS We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were Lactobacillus followed by Bifidobacterium and Lactococcus. In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity. CONCLUSION Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs.
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Affiliation(s)
- Hai Yun Shi
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China
| | - Xi Zhu
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wei Lin Li
- Department of Medicine, Division of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Sunny H Wong
- Department of Medicine and Therapeutics, State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Sheng Tao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China
| | - Shui Long Guo
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China
| | - Francis K L Chan
- Department of Medicine and Therapeutics, State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC) Limited, The Chinese University of Hong Kong, Hong Kong, China
| | - Shu Tian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- Microbiota I-Center (MagIC) Limited, The Chinese University of Hong Kong, Hong Kong, China.
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28
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Abstract
PURPOSE OF REVIEW Research in the past decade has revealed important implications for the microbiome in human health. Studies have defined a distinct gut microbiota in kidney transplant recipients and have recently linked the microbiota to infectious complications, similar to the allogeneic stem cell transplant population. RECENT FINDINGS In this review, we focus on the metabolism of immunosuppressive medications by the gut microbiota and on the urinary microbiome in the setting of infectious and immunological complications. We highlight seminal studies showing the role of specific gut microbiota in the direct metabolism of tacrolimus into a lesser effective immunosuppressant as well as the role of the gut microbiota in the metabolism of mycophenolic acid (MPA) glucuronide. We describe distinct urinary microbiota patterns in kidney transplant recipients with interstitial fibrosis tubular atrophy, chronic allograft nephropathy, tolerance, and bacterial and viral complications. SUMMARY The microbiota has important implications for immunosuppressive medications and immunological outcomes in kidney transplant recipients. Further research is needed to better delineate the impact of the metabolism of tacrolimus and MPA by gut bacteria and the role of the urine microbiota in the development of immunological and infectious complications.
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Affiliation(s)
| | | | - Tarek Barbar
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine
| | - John R Lee
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine
- Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York, USA
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29
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Winichakoon P, Chaiwarith R, Chattipakorn N, Chattipakorn SC. Impact of gut microbiota on kidney transplantation. Transplant Rev (Orlando) 2021; 36:100668. [PMID: 34688985 DOI: 10.1016/j.trre.2021.100668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 09/29/2021] [Accepted: 10/12/2021] [Indexed: 12/18/2022]
Abstract
Kidney transplantation is recognized as one of the most effective treatments for patients who suffer from end-stage renal disease. The major potential outcomes following kidney transplantation include engraftment, rejection, and associated complications. The outcomes are dependent on a variety of factors in those who underwent renal grafts or kidney transplant recipients. Those factors include the administration of immunosuppressive drugs and prophylactic antimicrobial agents to recipients. Recent studies have shown that gut microbiota play an important role in the outcome of subjects with kidney transplantation. An imbalance of the components/diversity of gut microbiota, known as gut dysbiosis, has been shown to have a big impact on the immune system of the host and the modification of host inflammatory cytokines. Although gut dysbiosis is affected by variation in diet and medication, a substantial amount of evidence showing a link between alteration in human gut microbiota and outcomes of kidney transplantation has recently been reported. Therefore, the objective of this review is to comprehensively summarize and discuss the major findings from in vivo and clinical data pertaining to the impact of gut microbiota on kidney transplantation. Any controversial findings are compiled to enable a clear overview of the role of gut microbiota and the outcome of kidney transplantation.
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Affiliation(s)
- Poramed Winichakoon
- Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand
| | - Romanee Chaiwarith
- Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand
| | - Nipon Chattipakorn
- Neuroelectrophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siriporn C Chattipakorn
- Neuroelectrophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
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30
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Chen J, Hall S, Vitetta L. Altered gut microbial metabolites could mediate the effects of risk factors in Covid-19. Rev Med Virol 2021; 31:1-13. [PMID: 34546607 PMCID: PMC7995004 DOI: 10.1002/rmv.2211] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/08/2020] [Accepted: 12/09/2020] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is now pandemic. While most Covid-19 patients will experience mild symptoms, a small proportion will develop severe disease, which could be fatal. Clinically, Covid-19 patients manifest fever with dry cough, fatigue and dyspnoea, and in severe cases develop into acute respiratory distress syndrome (ARDS), sepsis and multi-organ failure. These severe patients are characterized by hyperinflammation with highly increased pro-inflammatory cytokines including IL-6, IL-17 and TNF-alpha as well as C-reactive protein, which are accompanied by decreased lymphocyte counts. Clinical evidence supports that gut microbiota dysregulation is common in Covid-19 and plays a key role in the pathogenesis of Covid-19. In this narrative review, we summarize the roles of intestinal dysbiosis in Covid-19 pathogenesis and posit that the associated mechanisms are being mediated by gut bacterial metabolites. Based on this premise, we propose possible clinical implications. Various risk factors could be causal for severe Covid-19, and these include advanced age, concomitant chronic disease, SARS-CoV-2 infection of enterocytes, use of antibiotics and psychological distress. Gut dysbiosis is associated with risk factors and severe Covid-19 due to decreased commensal microbial metabolites, which cause reduced anti-inflammatory mechanisms and chronic low-grade inflammation. The preconditioned immune dysregulation enables SARS-CoV-2 infection to progress to an uncontrolled hyperinflammatory response. Thus, a pre-existing gut microbiota that is diverse and abundant could be beneficial for the prevention of severe Covid-19, and supplementation with commensal microbial metabolites may facilitate and augment the treatment of severe Covid-19.
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Affiliation(s)
| | - Sean Hall
- Research DepartmentMedlab ClinicalSydneyAustralia
| | - Luis Vitetta
- Research DepartmentMedlab ClinicalSydneyAustralia
- Faculty of Medicine and HealthThe University of SydneySydneyAustralia
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31
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Yang M, Yang Y, He Q, Zhu P, Liu M, Xu J, Zhao M. Intestinal Microbiota-A Promising Target for Antiviral Therapy? Front Immunol 2021; 12:676232. [PMID: 34054866 PMCID: PMC8149780 DOI: 10.3389/fimmu.2021.676232] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/28/2021] [Indexed: 12/12/2022] Open
Abstract
The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.
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Affiliation(s)
- Mengling Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yang Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Qingnan He
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Ping Zhu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Mengqi Liu
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jiahao Xu
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Mingyi Zhao
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
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32
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Pirozzolo I, Li Z, Sepulveda M, Alegre ML. Influence of the microbiome on solid organ transplant survival. J Heart Lung Transplant 2021; 40:745-753. [PMID: 34030971 DOI: 10.1016/j.healun.2021.04.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/06/2021] [Accepted: 04/11/2021] [Indexed: 10/21/2022] Open
Abstract
The microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping anticancer immunity, autoimmunity, and transplant responses. The focus of this review is to discuss recent findings tying the microbiota to transplant outcomes and alloimmunity. The microbiota changes dynamically following transplantation, but whether these changes affect transplant outcomes can be difficult to parse out. New data reveal effects of the microbiota locally, as well as systemically, depending on the mucosal/epithelial surface colonized, the specific commensal communities present and the nature of microbial-derived molecules produced. These complex interactions result in the microbiota potentially impacting transplantation at different levels, including modulation of donor and/or recipient cells, alterations in the priming and/or effector phases of the alloimmune response, availability or metabolism of immunosuppressive drugs, transplant fate or post-transplant complications.
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Affiliation(s)
- Isabella Pirozzolo
- Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Zhipeng Li
- Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Martin Sepulveda
- Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Maria-Luisa Alegre
- Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois.
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33
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Salvadori M, Tsalouchos A. Microbiota, renal disease and renal transplantation. World J Transplant 2021; 11:16-36. [PMID: 33816144 PMCID: PMC8009061 DOI: 10.5500/wjt.v11.i3.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/06/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation. The microbiota has a relevant role in conditioning the healthy status and the diseases. In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system. The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear. This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins. Similarly, after renal trans-plantation the microbiota changes with the appearance of pathobionts, principally in the first period because of the assumption of immunosuppressive drugs and antibiotics. These changes may deeply interfere with the graft outcome causing acute rejection, renal infections, diarrhea, and renal interstitial fibrosis. In addition, change in the microbiota may modify the metabolism of immuno-suppressive drugs causing in some patients the need of modifying the immunosuppressant dosing. The restoration of the indigenous microbiota after transplantation is important, either to avoiding the complications that impair the normal renal graft, and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft. The use of prebiotics, probiotics, smart bacteria and diet modification may restore the indigenous microbiota, but these studies are just at their beginning and more data are needed to draw definitive conclusions.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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34
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Huang J, Salinas T, Westblade LF, Lee JR. The Potential Role of the Gut Microbiota in Kidney Transplantation. KIDNEY360 2021; 2:890-893. [PMID: 35373069 PMCID: PMC8791346 DOI: 10.34067/kid.0006912020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 03/05/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Jennifer Huang
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Thalia Salinas
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Lars F. Westblade
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York
| | - John R. Lee
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, New York,Department of Transplantation Medicine, New York Presbyterian Hospital Weill Cornell Medical Center, New York, New York
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35
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Nishimoto A, Wohlgemuth N, Rosch J, Schultz-Cherry S, Cortez V, Rowe HM. Transkingdom Interactions Important for the Pathogenesis of Human Viruses. J Infect Dis 2020; 223:S201-S208. [PMID: 33330907 DOI: 10.1093/infdis/jiaa735] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The bacterial, fungal, and helminthic species that comprise the microbiome of the mammalian host have profound effects on health and disease. Pathogenic viruses must contend with the microbiome during infection and likely have evolved to exploit or evade the microbiome. Both direct interactions between the virions and the microbiota and immunomodulation and tissue remodeling caused by the microbiome alter viral pathogenesis in either host- or virus-beneficial ways. Recent insights from in vitro and murine models of viral pathogenesis have highlighted synergistic and antagonistic, direct and indirect interactions between the microbiome and pathogenic viruses. This review will focus on the transkingdom interactions between human gastrointestinal and respiratory viruses and the constituent microbiome of those tissues.
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Affiliation(s)
- Andrew Nishimoto
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Nicholas Wohlgemuth
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Jason Rosch
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Stacey Schultz-Cherry
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Valerie Cortez
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Hannah M Rowe
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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36
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Haak BW, Westendorp WF, van Engelen TSR, Brands X, Brouwer MC, Vermeij JD, Hugenholtz F, Verhoeven A, Derks RJ, Giera M, Nederkoorn PJ, de Vos WM, van de Beek D, Wiersinga WJ. Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case-Control Study. Transl Stroke Res 2020; 12:581-592. [PMID: 33052545 PMCID: PMC8213601 DOI: 10.1007/s12975-020-00863-4] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/01/2020] [Accepted: 10/04/2020] [Indexed: 02/07/2023]
Abstract
In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case-control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67-75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62-80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.
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Affiliation(s)
- Bastiaan W Haak
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Willeke F Westendorp
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands
| | - Tjitske S R van Engelen
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Xanthe Brands
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Matthijs C Brouwer
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands
| | - Jan-Dirk Vermeij
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands
| | - Floor Hugenholtz
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Aswin Verhoeven
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Rico J Derks
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Martin Giera
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Paul J Nederkoorn
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands
| | - Willem M de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
- Human Microbiome Research Program, Faculty of Medicine, Helsinki University, Helsinski, Finland
| | - Diederik van de Beek
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands.
| | - W Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC,, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Department of Medicine, Division of Infectious Diseases, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
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37
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Kaneko K, Akagawa S, Akagawa Y, Kimata T, Tsuji S. Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota. Front Immunol 2020; 11:1616. [PMID: 32793240 PMCID: PMC7393004 DOI: 10.3389/fimmu.2020.01616] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 06/17/2020] [Indexed: 12/19/2022] Open
Abstract
Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naïve at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD.
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Affiliation(s)
- Kazunari Kaneko
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
| | - Shohei Akagawa
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
| | - Yuko Akagawa
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
| | - Takahisa Kimata
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
| | - Shoji Tsuji
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
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Markey KA, Schluter J, Gomes ALC, Littmann ER, Pickard AJ, Taylor BP, Giardina PA, Weber D, Dai A, Docampo MD, Armijo GK, Slingerland AE, Slingerland JB, Nichols KB, Brereton DG, Clurman AG, Ramos RJ, Rao A, Bush A, Bohannon L, Covington M, Lew MV, Rizzieri DA, Chao N, Maloy M, Cho C, Politikos I, Giralt S, Taur Y, Pamer EG, Holler E, Perales MA, Ponce DM, Devlin SM, Xavier J, Sung AD, Peled JU, Cross JR, van den Brink MRM. The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD. Blood 2020; 136:130-136. [PMID: 32430495 PMCID: PMC7332893 DOI: 10.1182/blood.2019003369] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 04/19/2020] [Indexed: 01/10/2023] Open
Abstract
Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.
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Affiliation(s)
- Kate A Markey
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | | | - Antonio L C Gomes
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eric R Littmann
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amanda J Pickard
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | | | - Paul A Giardina
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Daniela Weber
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - Anqi Dai
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Melissa D Docampo
- Department of Medicine, Weill Cornell Medical College, New York, NY
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gabriel K Armijo
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ann E Slingerland
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - John B Slingerland
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Katherine B Nichols
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Daniel G Brereton
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Annelie G Clurman
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ruben J Ramos
- Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Arka Rao
- Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amy Bush
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Lauren Bohannon
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Megan Covington
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Meagan V Lew
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - David A Rizzieri
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Nelson Chao
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Molly Maloy
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Christina Cho
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Ioannis Politikos
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Sergio Giralt
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Ying Taur
- Department of Medicine, Weill Cornell Medical College, New York, NY
- Infectious Disease Service, Department of Medicine, and
| | - Eric G Pamer
- Department of Medicine, Weill Cornell Medical College, New York, NY
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
- Infectious Disease Service, Department of Medicine, and
| | - Ernst Holler
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - Miguel-Angel Perales
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Doris M Ponce
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sean M Devlin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Joao Xavier
- Program for Computational and Systems Biology, and
| | - Anthony D Sung
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and
| | - Jonathan U Peled
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Justin R Cross
- Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Marcel R M van den Brink
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
- Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
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39
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Sorbara MT, Littmann ER, Fontana E, Moody TU, Kohout CE, Gjonbalaj M, Eaton V, Seok R, Leiner IM, Pamer EG. Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity. Cell Host Microbe 2020; 28:134-146.e4. [PMID: 32492369 DOI: 10.1016/j.chom.2020.05.005] [Citation(s) in RCA: 264] [Impact Index Per Article: 52.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/11/2020] [Accepted: 05/06/2020] [Indexed: 02/03/2023]
Abstract
Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inter- and intra-species diversity in pathways that likely influence an isolate's ability to impact host health. These differences are likely to impact colonization resistance through lantibiotic expression or intestinal acidification, influence host mucosal immune cells and enterocytes via butyrate production, or contribute to synergism within a consortium by heterogenous polysaccharide metabolism. Identification of these specific functions could facilitate development of probiotic bacterial consortia that drive and/or restore in vivo microbiome functions.
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Affiliation(s)
- Matthew T Sorbara
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Infectious Diseases and Global Health, The University of Chicago, Chicago, IL 60637, USA.
| | - Eric R Littmann
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Emily Fontana
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Thomas U Moody
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Claire E Kohout
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Mergim Gjonbalaj
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vincent Eaton
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ruth Seok
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ingrid M Leiner
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Eric G Pamer
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Infectious Diseases and Global Health, The University of Chicago, Chicago, IL 60637, USA.
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40
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Satlin MJ, Westblade LF, Lee JR. Avoiding infections in transplant recipients: does the gut microbiota have a key role? Expert Rev Clin Immunol 2020; 16:113-115. [PMID: 31851851 DOI: 10.1080/1744666x.2019.1706485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Michael J Satlin
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Lars F Westblade
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - John R Lee
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
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41
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Lee JR, Huang J, Magruder M, Zhang LT, Gong C, Sholi AN, Albakry S, Edusei E, Muthukumar T, Lubetzky M, Dadhania DM, Taur Y, Pamer EG, Suthanthiran M. Butyrate-producing gut bacteria and viral infections in kidney transplant recipients: A pilot study. Transpl Infect Dis 2019; 21:e13180. [PMID: 31544324 PMCID: PMC6917841 DOI: 10.1111/tid.13180] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 09/14/2019] [Indexed: 02/06/2023]
Abstract
Background The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate‐producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients. Methods We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3 months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4‐V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al study. Results Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P = .01) but not with less development of CMV viremia (HR: 0.38, P = .13) or BK viremia (HR: 1.02, P = .98) at 2 years post transplantation. Conclusion Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.
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Affiliation(s)
- John R Lee
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, NewYork-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
| | - Jennifer Huang
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Matthew Magruder
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Lisa T Zhang
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Catherine Gong
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Adam N Sholi
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Shady Albakry
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Emmanuel Edusei
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Thangamani Muthukumar
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, NewYork-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
| | - Michelle Lubetzky
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, NewYork-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
| | - Darshana M Dadhania
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, NewYork-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
| | - Ying Taur
- Infectious Disease Service, Department of Medicine, Memsorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eric G Pamer
- Infectious Disease Service, Department of Medicine, Memsorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Manikkam Suthanthiran
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.,Department of Transplantation Medicine, NewYork-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA
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