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Li J, Gao F, Li R, Chen Z, Chen G, Fan P, Du G. Endoscopic surgery affects the gut microbiota and its metabolism in breast cancer patients. Front Microbiol 2025; 15:1481582. [PMID: 39839115 PMCID: PMC11747589 DOI: 10.3389/fmicb.2024.1481582] [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: 08/19/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025] Open
Abstract
Background Despite the advantages of endoscopic surgery in reducing trauma and enhancing recovery for breast cancer patients, its impact on gut microbiota, which is crucial for health and estrogen metabolism, remains unclear. Further investigation is necessary to fully understand this impact and its implications. Materials and methods Between June and December 2022, fecal samples were collected from 20 patients who underwent endoscopic surgery. The gut microbiota composition was determined using 16S rRNA sequencing, while the metabolites were analyzed through liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics and statistical analyses were employed to identify significant alterations in microbial taxa abundance and to assess intergroup differences. These analyses included t-tests for pairwise comparisons, one-way ANOVA for multiple group comparisons, and chi-square tests for categorical data analysis. Results Endoscopic surgery in breast cancer patients subtly changed gut microbiota diversity and composition. Post-surgery, there was a reduction in Lachnospiraceae, Monoglobaceae and Firmicutes to Bacteroides ratios. Shifts in metabolites were also observed, the changed metabolites impacted pathways such as primary bile biosynthesis and Ascorbate and aldarate metabolism, with PE(PGD1/18:1(9Z)) identified as a key differential metabolite that increased post-surgery. Azasetron, tyramine glucuronide, DL-DOPA, phthalide, acetophenazine, aciclovir, creatinine bicarbonate, and 4-oxo-L-proline being associated with distinct bacterial taxa. Conclusion Breast cancer patients undergoing endoscopic surgery experience a shift in their gut microbiota and metabolic profiles. Therefore, postoperative management, with a particular focus on the adjustment of the gut microbiota, is crucial for enhancing patient recovery and health outcomes.
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Affiliation(s)
- Jingtai Li
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Fangfang Gao
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Runwei Li
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China
| | - Zhilin Chen
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Guoping Chen
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Pingming Fan
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Guankui Du
- The First Clinical School of Hainan Medical University, Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China
- Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China
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Mohamed ME, Saqr A, Staley C, Onyeaghala G, Teigen L, Dorr CR, Remmel RP, Guan W, Oetting WS, Matas AJ, Israni AK, Jacobson PA. Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation. Transplantation 2024; 108:1895-1910. [PMID: 38361239 PMCID: PMC11327386 DOI: 10.1097/tp.0000000000004926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.
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Affiliation(s)
- Moataz E Mohamed
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN
| | - Abdelrahman Saqr
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN
| | | | - Guillaume Onyeaghala
- Hennepin Healthcare Research Institute, Minneapolis, MN
- Department of Medicine, University of Minnesota, Minneapolis, MN
| | - Levi Teigen
- Department of Food Science and Nutrition, University of Minnesota, St Paul, MN
| | - Casey R Dorr
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN
- Hennepin Healthcare Research Institute, Minneapolis, MN
- Department of Medicine, University of Minnesota, Minneapolis, MN
- Department of Medicine, Hennepin Healthcare, Minneapolis, MN
| | - Rory P Remmel
- Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN
| | - Weihua Guan
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN
| | - William S Oetting
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN
| | - Arthur J Matas
- Department of Surgery, University of Minnesota, Minneapolis, MN
| | - Ajay K Israni
- Hennepin Healthcare Research Institute, Minneapolis, MN
- Department of Medicine, Hennepin Healthcare, Minneapolis, MN
- Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
| | - Pamala A Jacobson
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN
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Chen G, Hu X, Huang Y, Xiang X, Pan S, Chen R, Xu X. Role of the immune system in liver transplantation and its implications for therapeutic interventions. MedComm (Beijing) 2023; 4:e444. [PMID: 38098611 PMCID: PMC10719430 DOI: 10.1002/mco2.444] [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: 05/07/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 12/17/2023] Open
Abstract
Liver transplantation (LT) stands as the gold standard for treating end-stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia-reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's immune microenvironment, with a specific focus on macrophages and T cells as primary immune players. Delving into the immunological dynamics at different stages of LT, we explore the disruptions after LT and subsequent immune responses. Focusing on immune cell targeting for treating liver transplant complications, we provide a comprehensive summary of ongoing clinical trials in this domain, especially cell therapies. Furthermore, we offer innovative treatment strategies that leverage the opportunities and prospects identified in the therapeutic landscape. This review seeks to advance our understanding of LT immunology and steer the development of precise therapies for postoperative complications.
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Affiliation(s)
- Guanrong Chen
- The Fourth School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Xin Hu
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Yingchen Huang
- The Fourth School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Xiaonan Xiang
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Sheng Pan
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Ronggao Chen
- Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Xiao Xu
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
- Zhejiang Chinese Medical UniversityHangzhouChina
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Cooper TE, Khalid R, Chan S, Craig JC, Hawley CM, Howell M, Johnson DW, Jaure A, Teixeira-Pinto A, Wong G. Synbiotics, prebiotics and probiotics for people with chronic kidney disease. Cochrane Database Syst Rev 2023; 10:CD013631. [PMID: 37870148 PMCID: PMC10591284 DOI: 10.1002/14651858.cd013631.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability). OBJECTIVES This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 μg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment. AUTHORS' CONCLUSIONS We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.
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Affiliation(s)
- Tess E Cooper
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Rabia Khalid
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Samuel Chan
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Allison Jaure
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Germaine Wong
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia
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5
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Abenavoli L, Scarlata GGM, Paravati MR, Boccuto L, Luzza F, Scarpellini E. Gut Microbiota and Liver Transplantation: Immune Mechanisms behind the Rejection. Biomedicines 2023; 11:1792. [PMID: 37509432 PMCID: PMC10376769 DOI: 10.3390/biomedicines11071792] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/17/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
Liver transplantation (LT) is the treatment of choice for patients with cirrhosis, decompensated disease, acute liver failure, and hepatocellular carcinoma (HCC). In 3-25% of cases, an alarming problem is acute and chronic cellular rejection after LT, and this event can lead to the need for new transplantation or the death of the patient. On the other hand, gut microbiota is involved in several mechanisms sustaining the model of the "gut-liver axis". These include modulation of the immune response, which is altered in case of gut dysbiosis, possibly resulting in acute graft rejection. Some studies have evaluated the composition of the gut microbiota in cirrhotic patients before and after LT, but few of them have assessed its impact on liver rejection. This review underlines the changes in gut microbiota composition before and after liver transplantation, hypothesizing possible immune mechanisms linking dysbiosis to transplantation rejection. Evaluation of changes in the gut microbiota composition in these patients is therefore essential in order to monitor the success of LT and eventually adopt appropriate preventive measures.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, University "Magna Graecia", 88100 Catanzaro, Italy
| | | | | | - Luigi Boccuto
- School of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USA
- School of Health Research, Clemson University, Clemson, SC 29634, USA
| | - Francesco Luzza
- Department of Health Sciences, University "Magna Graecia", 88100 Catanzaro, Italy
| | - Emidio Scarpellini
- Translationeel Onderzoek van Gastro-Enterologische Aandoeningen (TARGID.), Gasthuisberg University Hospital, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
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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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Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev 2022; 9:CD014804. [PMID: 36126902 PMCID: PMC9489278 DOI: 10.1002/14651858.cd014804.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut). OBJECTIVES To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation. SEARCH METHODS We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I² = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I² = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I² = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I² = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics. AUTHORS' CONCLUSIONS This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.
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Affiliation(s)
- Tess E Cooper
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Nicole Scholes-Robertson
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
- Translational Research Institute, Brisbane , Australia
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Allison Jaure
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Germaine Wong
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia
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Obrestad K, Einum S, Vadstein O. Stochastic variation in gut bacterial community affects reproductive rates in the water flea Daphnia magna. FEMS Microbiol Ecol 2022; 98:6693933. [PMID: 36073495 PMCID: PMC9550005 DOI: 10.1093/femsec/fiac105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 08/21/2022] [Accepted: 09/05/2022] [Indexed: 12/14/2022] Open
Abstract
It is well-documented that perturbation of the gut bacterial community can influence the reproductive rates of the host. Less is known about how natural ecological processes can change the bacterial composition in the gut and how such changes influence the reproductive rate of the host. Here, we provide novel experimental insights into such processes using the clonally reproducing water flea, Daphnia magna. A total of 20 replicate cultures were reared for 5 weeks (Phase 1) to allow for divergence of bacterial communities through stochastic processes (i.e. drift, founder effects, and/or colonization). Duplicate cultures created from each of these were reared for 21 days (Phase 2) while recording reproductive rates. There was a significant repeatability in reproductive rates between these duplicates, suggesting that divergence of the bacterial communities during Phase 1 translated into reproductive rate effects during Phase 2. This was further supported by significant differences in the relative abundance of gut bacteria (investigated by amplicon sequencing of a part of the 16S rRNA gene) between cultures with high and low reproductive rate in Phase 2. These results are consistent with the hypothesis that stochastic processes can cause natural variation in the bacterial composition in the gut, which in turn affect host reproductive rates.
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Affiliation(s)
- Kathrine Obrestad
- Corresponding author: Department of Biotechnology and Food Science, NTNU - Norwegian University of Science and Technology, 7491 Trondheim Norway. E-mail:
| | - Sigurd Einum
- Centre for Biodiversity Dynamics, Department of Biology, NTNU - Norwegian University of Science and Technology, 7491 Trondheim, Norway
| | - Olav Vadstein
- Corresponding author: Department of Biotechnology and Food Science, NTNU - Norwegian University of Science and Technology, 7491 Trondheim Norway. E-mail:
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9
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Priscilla C, Kumar S, Kumar CG, Parameswaran S, Viswanathan P, Ganesh RN. Pre-transplant Ratio of Firmicutes/Bacteroidetes of Gut Microbiota as a Potential Biomarker of Allograft Rejection in Renal Transplant Recipients. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022; 16:1799-1808. [DOI: 10.22207/jpam.16.3.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The advent of technologies has made allogenic transplantation a potential curative therapy for end-stage renal diseases, but the episodes of rejection still remain as one of the challenges in the post-transplant scenario. In the recent years, several human and animal studies have elucidated that gut microbial dysbiosis is closely linked with allogenic transplantation and post-transplant complications. But most of the studies focused on the use of high through-put sequencing technologies to analyze gut microbiota despite of its high cost, analysis and time constraints. Hence, in this work we aimed to study the impact of the two dominant gut phyla Firmicutes and Bacteroidetes on 38 renal transplant recipients, before and after transplantation and to find its association with allograft rejection. Significant changes (p<0.01) were observed in the relative abundances of the phyla Firmicutes and Bacteroidetes at pre- and post-transplant period. We have also found that the recipients who had an increase in Firmicutes/Bacteroidetes (F/B) ratio before transplant were highly prone to rejection in the first-year post-transplant. The Receiver Operating Characteristic (ROC) curve analysis has shown that the ratio of F/B were able to discriminate between rejection and non-rejection cases with an Area under the ROC Curve (AUC) of 0.91. Additionally, we observed that the ratio of F/B have reduced during the time of rejection postulating that gut microbial dysbiosis has more association with rejection. Thus, the assessment of F/B ratio using qPCR would be of a more practical approach for diagnosis and monitoring of graft function in a cost-effective and timely manner.
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10
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Wang Y, Gao X, Lv J, Zeng Y, Li Q, Wang L, Zhang Y, Gao W, Wang J. Gut Microbiome Signature Are Correlated With Bone Mineral Density Alterations in the Chinese Elders. Front Cell Infect Microbiol 2022; 12:827575. [PMID: 35433497 PMCID: PMC9008261 DOI: 10.3389/fcimb.2022.827575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 03/10/2022] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Osteoporosis (OP), clinically featured with a low bone mineral density (BMD) and high risk of bone fracture, has become a major risk factor of disability and death in the elders, especially in postmenopausal women. The gut microbiome (GM) is thought to be implicated in bone metabolism. Herein, we clarified the composition signature and gene functional profile of GM in older people with normal and low BMD. DESIGN AND METHODS A total of 455 participants underwent the BMD measurement and biochemical detection. GM analysis was further performed on 113 cases of postmenopausal women and men aged over 50, including both 16S rRNA and metagenomic sequencing. RESULTS Generally, the BMD value was significantly lower in the older age groups, especially in the postmenopausal women. Consistently, we observed obvious vitamin D deficiency or insufficiency in females (compared to the male, P < 0.0001). The results from 16S rRNA sequencing revealed higher numbers of OTUs and diversity indexes in females than in males. The abundance in composition of Firmicutes and Clostridiales were correlated with the BMD values in females. LEfSe analysis discovered several enriched bacteria taxons in OP and normal control (NC) subgroups. A positive correlation between the number of genes and BMD values was observed in females based on metagenomic sequencing analysis. Furthermore, we identified the connecting modules among the GM composition - gene functional signature - BMD value/T score in both females and males. CONCLUSIONS This study provides evidences upon which to understand the mechanisms of the effects of GM on bone health, consequently revealing the physiology status and potential diagnostic/therapeutic targets based on GM for OP and postmenopausal osteoporosis (PMOP). Besides, the status of vitamin D deficiency or insufficiency need to be concerned and improved in the Chinese people.
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Affiliation(s)
- Yangyang Wang
- School of Electronics and Information, Northwestern Polytechnical University, Xi’an, China
| | - Xiaoguang Gao
- School of Electronics and Information, Northwestern Polytechnical University, Xi’an, China
| | - Jing Lv
- Clinical Laboratory of Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yuhong Zeng
- Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Qingmei Li
- Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Liping Wang
- Department of Cardiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yuanyuan Zhang
- Department of Cardiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Wenjie Gao
- Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jihan Wang
- Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an, China
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11
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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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12
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Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Tong A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Hippokratia 2021. [DOI: 10.1002/14651858.cd014804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Tess E Cooper
- Cochrane Kidney and Transplant, Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Sydney School of Public Health; The University of Sydney; Sydney Australia
| | - Nicole Scholes-Robertson
- Cochrane Kidney and Transplant, Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- College of Medicine and Public Health; Flinders University; Adelaide Australia
| | - Carmel M Hawley
- Department of Nephrology; Princess Alexandra Hospital; Brisbane Australia
| | - Martin Howell
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - David W Johnson
- Department of Nephrology; Princess Alexandra Hospital; Brisbane Australia
- Australasian Kidney Trials Network; The University of Queensland; Brisbane Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Allison Tong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Germaine Wong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Centre for Transplant and Renal Research; Westmead Hospital; Westmead Australia
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13
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Qiu F, Lu W, Ye S, Liu H, Zeng Q, Huang H, Liang CL, Chen Y, Zheng F, Zhang Q, Lu CJ, Dai Z. Berberine Promotes Induction of Immunological Tolerance to an Allograft via Downregulating Memory CD8 + T-Cells Through Altering the Gut Microbiota. Front Immunol 2021; 12:646831. [PMID: 33643325 PMCID: PMC7907598 DOI: 10.3389/fimmu.2021.646831] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 01/26/2021] [Indexed: 12/14/2022] Open
Abstract
Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections.
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Affiliation(s)
- Feifei Qiu
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Weihui Lu
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shulin Ye
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huazhen Liu
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiaohuang Zeng
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haiding Huang
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chun-Ling Liang
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuchao Chen
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fang Zheng
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qunfang Zhang
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chuan-Jian Lu
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhenhua Dai
- Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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14
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Pabbathi NPP, Velidandi A, Tavarna T, Gupta S, Raj RS, Gandam PK, Baadhe RR. Role of metagenomics in prospecting novel endoglucanases, accentuating functional metagenomics approach in second-generation biofuel production: a review. BIOMASS CONVERSION AND BIOREFINERY 2021; 13:1371-1398. [PMID: 33437563 PMCID: PMC7790359 DOI: 10.1007/s13399-020-01186-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/30/2020] [Accepted: 12/01/2020] [Indexed: 05/02/2023]
Abstract
As the fossil fuel reserves are depleting rapidly, there is a need for alternate fuels to meet the day to day mounting energy demands. As fossil fuel started depleting, a quest for alternate forms of fuel was initiated and biofuel is one of its promising outcomes. First-generation biofuels are made from edible sources like vegetable oils, starch, and sugars. Second-generation biofuels (SGB) are derived from lignocellulosic crops and the third-generation involves algae for biofuel production. Technical challenges in the production of SGB are hampering its commercialization. Advanced molecular technologies like metagenomics can help in the discovery of novel lignocellulosic biomass-degrading enzymes for commercialization and industrial production of SGB. This review discusses the metagenomic outcomes to enlighten the importance of unexplored habitats for novel cellulolytic gene mining. It also emphasizes the potential of different metagenomic approaches to explore the uncultivable cellulose-degrading microbiome as well as cellulolytic enzymes associated with them. This review also includes effective pre-treatment technology and consolidated bioprocessing for efficient biofuel production.
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Affiliation(s)
- Ninian Prem Prashanth Pabbathi
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Aditya Velidandi
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Tanvi Tavarna
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Shreyash Gupta
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Ram Sarvesh Raj
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Pradeep Kumar Gandam
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
| | - Rama Raju Baadhe
- Integrated Biorefinery Research Lab, Department of Biotechnology, National Institute of Technology, Warangal, Telangana 506004 India
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15
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Cooper TE, Khalid R, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Tong A, Wong G. Synbiotics, prebiotics and probiotics for people with chronic kidney disease. Hippokratia 2020. [DOI: 10.1002/14651858.cd013631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Tess E Cooper
- Cochrane Kidney and Transplant, Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Sydney School of Public Health; The University of Sydney; Sydney Australia
| | - Rabia Khalid
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- College of Medicine and Public Health; Flinders University; Adelaide Australia
| | - Carmel M Hawley
- Department of Nephrology; Princess Alexandra Hospital; Brisbane Australia
| | - Martin Howell
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - David W Johnson
- Department of Nephrology; Princess Alexandra Hospital; Brisbane Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Allison Tong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
| | - Germaine Wong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Centre for Transplant and Renal Research; Westmead Hospital; Westmead Australia
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16
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Dery KJ, Kadono K, Hirao H, Górski A, Kupiec-Weglinski JW. Microbiota in organ transplantation: An immunological and therapeutic conundrum? Cell Immunol 2020; 351:104080. [PMID: 32139071 DOI: 10.1016/j.cellimm.2020.104080] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/23/2020] [Accepted: 02/25/2020] [Indexed: 12/15/2022]
Abstract
The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development of resistance against pathogens and the stabilization of mucosa-associated lymphoid tissue. The gut-microbiota axis may also precipitate allograft rejection by producing metabolites that activate host cell-mediated and humoral immunity. Here, we discuss new insights into microbial immunomodulation, highlighting ongoing attempts to affect commensal colonization in an attempt to ameliorate allograft rejection cascade. Recent progress on the use of antibiotics to modulate GI microbiota diversity and innate-adaptive immune interface are discussed. Our focus on the microbiota's influence of endoplasmic reticulum (ER) stress and autophagy signaling through hepatic EP4/CHOP/LC3B platforms reveals a novel molecular pathway and potential biomarkers determining the progression of allo-Tx damage. Understanding and harnessing the potential of microbiome/bacteriophage therapies may offer safe and effective means for personalized treatment to reduce risks of infections and immunosuppression in allo-Tx.
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Affiliation(s)
- Kenneth J Dery
- Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles 90095, CA, USA
| | - Kentaro Kadono
- Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles 90095, CA, USA
| | - Hirofumi Hirao
- Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles 90095, CA, USA
| | - Andrzej Górski
- Bacteriophage Laboratory and Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Jerzy W Kupiec-Weglinski
- Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles 90095, CA, USA.
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17
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Luján JA, Rugeles MT, Taborda NA. Contribution of the Microbiota to Intestinal Homeostasis and its Role in the Pathogenesis of HIV-1 Infection. Curr HIV Res 2020; 17:13-25. [PMID: 30854974 DOI: 10.2174/1570162x17666190311114808] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 02/25/2019] [Accepted: 03/06/2019] [Indexed: 12/18/2022]
Abstract
During HIV infection, massive destruction of CD4+ T cells ensues, preferentially depleting the Th17 subset at the gut-associated lymphoid tissue (GALT), leading to a loss of mucosal integrity and an increase in cell permeability. This process favors microbial translocation between the intestinal lumen and the circulatory system, contributing to persistent immune activation and chronic inflammation characteristic of HIV infection. Thus, the gut microbiota plays an integral role in maintaining the structure and function of the mucosal barrier, a critical factor for immune homeostasis. However, in the context of HIV infection, changes in the gut microbiota have been reported and have been linked to disease progression. Here, we review evidence for the role of the gut microbiota in intestinal homeostasis, its contribution to HIV pathogenesis, as well as its use in the development of therapeutic strategies.
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Affiliation(s)
- Jorge A Luján
- Grupo Inmunovirologia, Facultad de Medicina. Universidad de Antioquia, Medellin, Colombia
| | - Maria T Rugeles
- Grupo Inmunovirologia, Facultad de Medicina. Universidad de Antioquia, Medellin, Colombia
| | - Natalia A Taborda
- Grupo Inmunovirologia, Facultad de Medicina. Universidad de Antioquia, Medellin, Colombia.,Grupo de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, Medellín, Colombia
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18
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Colas L, Mongodin EF, Montassier E, Chesneau M, Guerif P, Hittle L, Giral M, Bromberg JS, Brouard S. Unique and specific Proteobacteria diversity in urinary microbiota of tolerant kidney transplanted recipients. Am J Transplant 2020; 20:145-158. [PMID: 31374143 DOI: 10.1111/ajt.15549] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 07/15/2019] [Accepted: 07/19/2019] [Indexed: 01/25/2023]
Abstract
Host-microbiota interactions can modulate the immune system both at local and systemic levels, with potential consequences for organ transplantation outcomes. In this study, we hypothesized that differences in the urinary microbiome following kidney transplantation would be associated with posttransplantation status: stable, minimally immunosuppressed, or tolerant. One hundred thirteen urine samples from stable (n = 51), minimally immunosuppressed (n = 19), and spontaneously tolerant (n = 16) patients, paired with age-matched controls (n = 27) were profiled and compared to each other at a taxonomic level with special interest in the immunosuppressive regimen. All comparisons and correlations were adjusted on sex and time posttransplantation. Our results highlighted a unique and specific urinary microbiota associated with spontaneous tolerance characterized by a high diversity and a clear Proteobacteria profile. Finally, we report that this profile is (1) impacted by gender, (2) inversely correlated with immunosuppressive drugs (calcineurin inhibitors and mammalian target of rapamycin inhibitors), and (3) stable in time.
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Affiliation(s)
- Luc Colas
- Plateforme Transversale d'Allergologie et d'Immunologie Clinique, Institut du Thorax, CHU de Nantes, Nantes, France
- Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
| | - Emmanuel F Mongodin
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland
| | | | - Mélanie Chesneau
- Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
| | - Pierrick Guerif
- Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
| | - Lauren Hittle
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland
| | - Magali Giral
- Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
| | - Jonathan S Bromberg
- Departments of Surgery and Microbiology and Immunology, and the Center for Vascular and Inflammatory Diseases, University of Maryland, School of Medicine, Baltimore, Maryland
| | - Sophie Brouard
- Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France
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Functional Microbiomics in Liver Transplantation: Identifying Novel Targets for Improving Allograft Outcomes. Transplantation 2019; 103:668-678. [PMID: 30507741 DOI: 10.1097/tp.0000000000002568] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gut dysbiosis, defined as a maladaptive gut microbial imbalance, has been demonstrated in patients with end-stage liver disease, defined as a contributor to disease progression, and associated clinically with severity of disease and liver-related morbidity and mortality. Despite this well-recognized phenomena in patients with end-stage liver disease, the impact of gut dysbiosis and its rate of recovery following liver transplantation (LT) remains incompletely understood. The mechanisms by which alterations in the gut microbiota impact allograft metabolism and immunity, both directly and indirectly, are multifactorial and reflect the complexity of the gut-liver axis. Importantly, while research has largely focused on quantitative and qualitative changes in gut microbial composition, changes in microbial functionality (in the presence or absence of compositional changes) are of critical importance. Therefore, to translate functional microbiomics into clinical practice, one must understand not only the compositional but also the functional changes associated with gut dysbiosis and its resolution post-LT. In this review, we will summarize critical advances in functional microbiomics in LT recipients as they apply to immune-mediated allograft injury, posttransplant complications, and disease recurrence, while highlighting potential areas for microbial-based therapeutics in LT recipients.
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Ligustrum robustum Intake, Weight Loss, and Gut Microbiota: An Intervention Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:4643074. [PMID: 31110550 PMCID: PMC6487153 DOI: 10.1155/2019/4643074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 02/17/2019] [Accepted: 03/10/2019] [Indexed: 12/05/2022]
Abstract
Ligustrum robustum (LR) shows antiobesity effects in animal studies. However, little is known about the effect on human. The present study aimed to investigate the effect of LR intake on weight change in obese women and the role of gut microbiota. Thirty overweight and obese female participants (BMI ≥24 kg/m2) were recruited in the current study. The participants drank LR 10g/d for 12 wks. Their body composition and related biomarkers were assessed. Alterations of the gut microbiota were analyzed using 16S rRNA sequencing. The primary outcome was the change in body weight. LR intake resulted in 2.5% weight loss over 12 wks (P<0.01). Change in body fat at 12 wk was -1.77 ± 1.19 kg (P<0.01). In addition, decreased Firmicutes-to-Bacteroidetes ratio (P=0.03), increased richness (the ACE estimator, P<0.01; the Chao1 estimator, P<0.01), and altered representative taxa of the gut microbiota were observed. Bacteroidaceae, Bacteroides, Bacilli, and Lactobacillales were higher while Ruminococcaceae, Enterobacteriaceae, Enterobacteriales, Lachnospiraceae, Clostridia, and Clostridiales were lower at 12 wk. Moreover, LR intervention decreased fasting glucose (P<0.01), serum leptin (P<0.01), and IL8 (P=0.02) and increased HOMA-β (P<0.01). LR intervention moderately decreased the body weight in overweight and obese women and such effect might be due to modulation of gut microbiota.
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Kriss M, Hazleton KZ, Nusbacher NM, Martin CG, Lozupone CA. Low diversity gut microbiota dysbiosis: drivers, functional implications and recovery. Curr Opin Microbiol 2018; 44:34-40. [PMID: 30036705 DOI: 10.1016/j.mib.2018.07.003] [Citation(s) in RCA: 262] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 06/07/2018] [Accepted: 07/11/2018] [Indexed: 02/07/2023]
Abstract
Dysbiosis, an imbalance in microbial communities, is linked with disease when this imbalance disturbs microbiota functions essential for maintaining health or introduces processes that promote disease. Dysbiosis in disease is predicted when microbiota differ compositionally from a healthy control population, but only truly defined when these differences are mechanistically related to adverse phenotypes. For the human gut microbiota, dysbiosis varies across diseases. One common manifestation is replacement of the complex community of anaerobes typical of the healthy adult gut microbiome with a community of lower overall microbial diversity and increased facultative anaerobes. Here we review diseases in which low-diversity dysbiosis has been observed and mechanistically linked with disease, with a particular focus on liver disease, inflammatory bowel disease, and Clostridium difficile infection.
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Affiliation(s)
- Michael Kriss
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, 12700 East 19th Avenue, Campus Box B146, Aurora, CO 80045, USA
| | - Keith Z Hazleton
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA; Digestive Health Institute, Children's Hospital Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA
| | - Nichole M Nusbacher
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado, 12700 East 19th Avenue, Campus Box 8617, Aurora, CO 80045, USA
| | - Casey G Martin
- Department of Immunology and Microbiology, University of Colorado, 12700 East 19th Avenue,Campus Box 8617, Aurora, CO 80045, USA
| | - Catherine A Lozupone
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado, 12700 East 19th Avenue, Campus Box 8617, Aurora, CO 80045, USA.
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Li H, Qu J, Li T, Wirth S, Zhang Y, Zhao X, Li X. Diet simplification selects for high gut microbial diversity and strong fermenting ability in high-altitude pikas. Appl Microbiol Biotechnol 2018; 102:6739-6751. [PMID: 29862448 DOI: 10.1007/s00253-018-9097-z] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/12/2018] [Accepted: 05/15/2018] [Indexed: 02/06/2023]
Abstract
The gut microbiota in mammals plays a key role in host metabolism and adaptation. However, relatively little is known regarding to how the animals adapts to extreme environments through regulating gut microbial diversity and function. Here, we investigated the diet, gut microbiota, short-chain fatty acid (SCFA) profiles, and cellulolytic activity from two common pika (Ochotona spp.) species in China, including Plateau pika (Ochotona curzoniae) from the Qinghai-Tibet Plateau and Daurian pika (Ochotona daurica) from the Inner Mongolia Grassland. Despite a partial diet overlap, Plateau pikas harbored lower diet diversity than Daurian pikas. Some bacteria (e.g., Prevotella and Ruminococcus) associated with fiber degradation were enriched in Plateau pikas. They harbored higher gut microbial diversity, total SCFA concentration, and cellulolytic activity than Daurian pikas. Interestingly, cellulolytic activity was positively correlated with the gut microbial diversity and SCFAs. Gut microbial communities and SCFA profiles were segregated structurally between host species. PICRUSt metagenome predictions demonstrated that microbial genes involved in carbohydrate metabolism and energy metabolism were overrepresented in the gut microbiota of Plateau pikas. Our results demonstrate that Plateau pikas harbor a stronger fermenting ability for the plant-based diet than Daurian pikas via gut microbial fermentation. The enhanced ability for utilization of plant-based diets in Plateau pikas may be partly a kind of microbiota adaptation for more energy requirements in cold and hypoxic high-altitude environments.
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Affiliation(s)
- Huan Li
- Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Jiapeng Qu
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, Qinghai, People's Republic of China
| | - Tongtong Li
- Department of Applied Biology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Stephan Wirth
- Leibniz-Centre for Agricultural Landscape Research (ZALF), Institute of Landscape Biogeochemistry, Eberswalder Str. 84, 15374, Muncheberg, Germany
| | - Yanming Zhang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, Qinghai, People's Republic of China.
| | - Xinquan Zhao
- Key Laboratory of Environmental and Applied Microbiology, CAS; Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, Sichuan, People's Republic of China
| | - Xiangzhen Li
- Key Laboratory of Environmental and Applied Microbiology, CAS; Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, Sichuan, People's Republic of China.
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Abstract
The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.
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Pan W, Kang Y. Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies. Int Urol Nephrol 2018; 50:289-299. [PMID: 28849345 DOI: 10.1007/s11255-017-1689-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 08/23/2017] [Indexed: 02/05/2023]
Abstract
The complicated communities of microbiota colonizing the human gastrointestinal tract exert a strong function in health maintenance and disease prevention. Indeed, accumulating evidence has indicated that the intestinal microbiota plays a key role in the pathogenesis and development of chronic kidney disease (CKD). Modulation of the gut microbiome composition in CKD may contribute to the accumulation of gut-derived uremic toxins, high circulating level of lipopolysaccharides and immune deregulation, all of which play a critical role in the pathogenesis of CKD and CKD-associated complications. In this review, we discuss the recent findings on the potential impact of gut microbiota in CKD and the underlying mechanisms by which microbiota can influence kidney diseases and vice versa. Additionally, the potential efficacy of pre-, pro- and synbiotics in the restoration of healthy gut microbia is described in detail to provide future directions for research.
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Affiliation(s)
- Wei Pan
- Faculty of Foreign Languages and Cultures, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yongbo Kang
- Medical Faculty, Kunming University of Science and Technology, Kunming, Yunnan, China.
- Genetics and Pharmacogenomics Laboratory, Kunming University of Science and Technology, Kunming, Yunnan, China.
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25
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26
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Cui M, Xiao H, Li Y, Zhou L, Zhao S, Luo D, Zheng Q, Dong J, Zhao Y, Zhang X, Zhang J, Lu L, Wang H, Fan S. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med 2017; 9:448-461. [PMID: 28242755 PMCID: PMC5376756 DOI: 10.15252/emmm.201606932] [Citation(s) in RCA: 225] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Severe radiation exposure may cause acute radiation syndrome, a possibly fatal condition requiring effective therapy. Gut microbiota can be manipulated to fight against many diseases. We explored whether intestinal microbe transplantation could alleviate radiation‐induced toxicity. High‐throughput sequencing showed that gastrointestinal bacterial community composition differed between male and female mice and was associated with susceptibility to radiation toxicity. Faecal microbiota transplantation (FMT) increased the survival rate of irradiated animals, elevated peripheral white blood cell counts and improved gastrointestinal tract function and intestinal epithelial integrity in irradiated male and female mice. FMT preserved the intestinal bacterial composition and retained mRNA and long non‐coding RNA expression profiles of host small intestines in a sex‐specific fashion. Despite promoting angiogenesis, sex‐matched FMT did not accelerate the proliferation of cancer cells in vivo. FMT might serve as a therapeutic to mitigate radiation‐induced toxicity and improve the prognosis of tumour patients after radiotherapy.
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Affiliation(s)
- Ming Cui
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Huiwen Xiao
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Yuan Li
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Lixin Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Shuyi Zhao
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Dan Luo
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Qisheng Zheng
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Jiali Dong
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Yu Zhao
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Xin Zhang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Junling Zhang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Lu Lu
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Haichao Wang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.,Department of Emergency Medicine, North Shore University Hospital, Laboratory of Emergency Medicine, the Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Saijun Fan
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
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27
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Ardalan M, Vahed SZ. Gut microbiota and renal transplant outcome. Biomed Pharmacother 2017; 90:229-236. [DOI: 10.1016/j.biopha.2017.02.114] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 02/26/2017] [Accepted: 02/28/2017] [Indexed: 02/07/2023] Open
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Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation. Transplant Direct 2017; 3:e144. [PMID: 28405600 PMCID: PMC5381737 DOI: 10.1097/txd.0000000000000661] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 01/24/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. METHODS We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. RESULTS Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. CONCLUSIONS The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.
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30
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Georgel P. Innate immune receptors in solid organ transplantation. Hum Immunol 2016; 77:1071-1075. [DOI: 10.1016/j.humimm.2016.04.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 03/18/2016] [Accepted: 04/04/2016] [Indexed: 12/13/2022]
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Cigarran Guldris S, González Parra E, Cases Amenós A. Gut microbiota in chronic kidney disease. Nefrologia 2016; 37:9-19. [PMID: 27553986 DOI: 10.1016/j.nefro.2016.05.008] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 04/25/2016] [Accepted: 05/10/2016] [Indexed: 02/06/2023] Open
Abstract
The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases. In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD. This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.
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Affiliation(s)
| | - Emilio González Parra
- Servicio de Nefrología, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, España
| | - Aleix Cases Amenós
- Servicio de Nefrología, Hospital Clinic, Universitat de Barcelona, Barcelona, España
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32
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Shankar J, Nguyen MH, Crespo MM, Kwak EJ, Lucas SK, McHugh KJ, Mounaud S, Alcorn JF, Pilewski JM, Shigemura N, Kolls JK, Nierman WC, Clancy CJ. Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients. Am J Transplant 2016; 16:1766-78. [PMID: 26693965 DOI: 10.1111/ajt.13676] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 11/10/2015] [Accepted: 12/06/2015] [Indexed: 01/25/2023]
Abstract
Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.
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Affiliation(s)
- J Shankar
- J. Craig Venter Institute, Rockville, MD
| | - M H Nguyen
- Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - M M Crespo
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - E J Kwak
- Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - S K Lucas
- J. Craig Venter Institute, Rockville, MD
| | - K J McHugh
- Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA
| | - S Mounaud
- J. Craig Venter Institute, Rockville, MD
| | - J F Alcorn
- Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA
| | - J M Pilewski
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - N Shigemura
- Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA
| | - J K Kolls
- Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - C J Clancy
- Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.,VA Pittsburgh Healthcare System, Division of Infectious Diseases, Pittsburgh, PA
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Pevsner-Fischer M, Tuganbaev T, Meijer M, Zhang SH, Zeng ZR, Chen MH, Elinav E. Role of the microbiome in non-gastrointestinal cancers. World J Clin Oncol 2016; 7:200-213. [PMID: 27081642 PMCID: PMC4826965 DOI: 10.5306/wjco.v7.i2.200] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Revised: 11/15/2015] [Accepted: 02/24/2016] [Indexed: 02/06/2023] Open
Abstract
“The forgotten organ”, the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as “local” and “systemic”, “cancer-stimulating” and “cancer-suppressing” effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment.
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Aron-Wisnewsky J, Clément K. The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat Rev Nephrol 2015; 12:169-81. [PMID: 26616538 DOI: 10.1038/nrneph.2015.191] [Citation(s) in RCA: 223] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cardiometabolic diseases (CMDs) have been associated with changes in the composition of the gut microbiota, with links between the host environment and microbiota identified in preclinical models. High-throughput sequencing technology has facilitated in-depth studies of the gut microbiota, bacterial-derived metabolites, and their association with CMDs. Such strategies have shown that patients with CMDs frequently exhibit enrichment or depletion of certain bacterial groups in their resident microbiota compared to healthy individuals. Furthermore, the ability to transfer resident gut microbiota from mice or humans into germ-free mouse models, or between human patients, has enabled researchers to characterize the causative role of the gut microbiota in CMDs. These approaches have helped identify that dietary intake of choline, which is metabolized by the gut microbiota, is associated with cardiovascular outcomes in mice and humans. Trimethylamine N-oxide (TMAO) - a metabolite derived from the gut microbiota - is also associated with poor cardiovascular outcomes in patients with cardiovascular disease and is elevated in patients with chronic kidney disease (CKD). TMAO might represent a biomarker that links the environment and microbiota with CKD. This Review summarizes data suggesting a link between the gut microbiota and derived metabolites with food intake patterns, metabolic alterations, and chronic CMDs.
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Affiliation(s)
- Judith Aron-Wisnewsky
- Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, INSERM, Sorbonne Université, Paris 6, Pitié-Salpêtrière hospital, F-75013 Paris, France
| | - Karine Clément
- Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, INSERM, Sorbonne Université, Paris 6, Pitié-Salpêtrière hospital, F-75013 Paris, France
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Galindo-Villegas J. Recent findings on vertebrate developmental immunity using the zebrafish model. Mol Immunol 2015; 69:106-12. [PMID: 26589453 DOI: 10.1016/j.molimm.2015.10.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 10/17/2015] [Accepted: 10/19/2015] [Indexed: 01/06/2023]
Abstract
To grant survival against sterile or microbe induced inflammation, all animals rely on correct immune system functioning. The development of immunity occurs in vertebrates during embryogenesis in a process called hematopoiesis, which is characterized by the formation of blood cellular components such as embryonic erythrocytes and primitive macrophages. These cells are formed in a sterile environment from a rare subset of pluripotent hematopoietic stem cells (HSC) during a brief period of the primitive hematopoietic wave. Diverse signals, like Notch, are indispensable in HSC emergence and differentiation. However, to successfully replicate the process in vitro using pluripotent precursors, the full set of required signals is still a matter of debate. Among the latest findings, proinflammatory signals produced by transient primitive myelocites in zebrafish have been seen to act as essential mediators in establishing the HSC program of the adult vertebrate hematopoietic system. In this regard, the zebrafish immune model has emerged as a feasible live vertebrate model for examining developmental immunity and related host-microbe interactions, both at the molecular and cellular level. Thus, using the zebrafish embryo, this review summarizes recent findings, on the signals required for immune development and further maturation of the system, in a context where no adaptive immune response has yet been developed.
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Affiliation(s)
- Jorge Galindo-Villegas
- Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain.
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Wang W, Xu S, Ren Z, Jiang J, Zheng S. Gut microbiota and allogeneic transplantation. J Transl Med 2015; 13:275. [PMID: 26298517 PMCID: PMC4546814 DOI: 10.1186/s12967-015-0640-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 08/14/2015] [Indexed: 02/06/2023] Open
Abstract
The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the relationship between gut microbiota and complications after allogeneic transplantation may make gut microbiota as a therapeutic target in the future.
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Affiliation(s)
- Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
| | - Shaoyan Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
| | - Zhigang Ren
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
| | - Jianwen Jiang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
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Dumont CM, Park J, Shea LD. Controlled release strategies for modulating immune responses to promote tissue regeneration. J Control Release 2015; 219:155-166. [PMID: 26264833 DOI: 10.1016/j.jconrel.2015.08.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Revised: 08/04/2015] [Accepted: 08/05/2015] [Indexed: 01/06/2023]
Abstract
Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti-inflammatory environment that leads to regeneration, and induce antigen (Ag)-specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno-modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations.
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Affiliation(s)
- Courtney M Dumont
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA
| | - Jonghyuck Park
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA
| | - Lonnie D Shea
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
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