Transplant associated infections—The role of the gastrointestinal microbiota and potential therapeutic options

Chan, Samuel; Hawley, Carmel M.; Campbell, Katrina L.; Morrison, Mark; Campbell, Scott; Isbel, Nicole M.; Francis, Ross; Playford, E Geoffrey; Johnson, David W.

doi:10.1111/nep.13670

Cited by 19 publications

(13 citation statements)

References 58 publications

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“…Another single-centre study undertaken in Canada involving 36 kidney transplant recipients who reported a two-week history of diarrhoea showed that in 30 out of the 36 cases, an infectious agent was found 23 . Thus, other mechanisms such as the role of the gastrointestinal microbiota [24][25][26] may explain the gastrointestinal symptoms reported in kidney transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation

Chan

Cao

Pascoe

et al. 2021

Kidney International Reports

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionmentioning

confidence: 99%

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation

Chan

Cao

Pascoe

et al. 2021

Kidney International Reports

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“…The patients in the Erpicum group received MSC treatment on D3±2 with a dose of approximately 1.5×10 6 -3×10 6 cells/kg [20] . The Sun group separately infused 2×10 6 cells/kg and 5×10 6 cells 30 min before surgery and during surgery [22] , while the Pan group chose to inject 5×10 6 MSCs during surgery, followed by 2×10 6 cells/kg on D30 [23] . The Tan group transplanted two doses of 1-2×10 6 cells/kg MSCs before surgery and on D14 postsurgery [21] .…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The long-term consumption of regular immunosuppressive drugs, including corticosteroids, calcineurin inhibitors (CNIs), antimetabolites, and sometimes lymphodepletion, can signi cantly increase the risk of some important adverse effects, such as nephrotoxicity, infection, tumorigenicity, diabetes and cardiovascular diseases, which can affect the long-term graft outcomes and can even sometimes be lifethreatening [1][2][3][4][5] . Infectious complications are common following KT and rank among the top ve causes of patient deaths with allograft function [6] . Despite great efforts in drug innovations, the drawbacks mentioned above have not yet been resolved, and the hazards affecting long-term graft survival have failed to substantially decrease [7] .…”

Section: Introductionmentioning

confidence: 99%

Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis

Zhao¹,

Han

et al. 2020

Preprint

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Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents and posttransplant complications.Methods PubMed, Embase, EBSCO, Ovid and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. Results Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR=0.65, 95% CI: 0.46-0.9, P=0.01),. There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR=0.77, 95% CI: 0.41–1.45, P=0.42), 1-year graft survival rate (RR=0.99, 95% CI: 0.95–1.03, P=0.74), delayed graft function (DGF) rate (RR=0.54, 95% CI: 0.21–1.38, P=0.2) and renal graft function at 1 month (MD=-1.56, 95% CI: -14.2– 11.08, p=0.81), 3 months (MD=0.15, 95% CI: -5.63– 5.93, p=0.96), 6 months (MD=-1.95, 95% CI: -9.87– 5.97, p=0.63), and 12 months (MD=-1.13, 95% CI: -7.16– 4.89, p=0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable. Conclusion Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter RCTs with large sample sizes and long follow-up periods.

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“…Interest regarding the relationship between the gastrointestinal microbiota and chronic diseases, such as diabetes mellitus, obesity and chronic kidney disease, has surged over the last 5 years 1‐6 . In the setting of kidney transplantation, changes in the gastrointestinal microbiota are hypothesized to be associated with various infections, 7‐10 but evidence to address the hypothesis is scant. In comparison, a longitudinal study of the gut microbiota from 38 liver transplant recipients at Kyoto University Hospital in Japan between June 2013 to September 2014, reported the relative abundance of Staphylococcus aureus , Enterococcus faecium , Escherichia coli and Pseudomonas aeruginosa were elevated in those acquiring bloodstream infections 11 .…”

Section: Introductionmentioning

confidence: 99%

Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients

et al. 2021

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Background There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery. Aim To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation. Methods Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing. Results The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post‐transplant, reflected in reductions of the mean (±SD) richness values (156 ± 46.5 to 116 ± 38.6, p = 0.002), and Shannon diversity (3.57 ± 0.49 to 3.14 ± 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post‐transplant (26‐fold increase from 0.16 ± 0.0091 to 4.6 ± 0.3; p = 0.006; FDR = 0.12). Functionally, the post‐transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2‐fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6‐fold; p = 0.006; FDR = 0.14). Conclusion Live donor kidney transplantation and standard care post‐transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.

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Transplant associated infections—The role of the gastrointestinal microbiota and potential therapeutic options

Cited by 19 publications

References 58 publications

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation

Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis

Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients

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