Abstract
Gaining long-term graft function and patient life quality remain critical challenges following kidney transplantation. Advances in immunology, gnotobiotics, and culture-independent molecular techniques have provided growing insights into the complex relationship of the microbiome and the host. However, little is known about the over time-shift of the gut microbiota in the context of kidney transplantation and its impact on both graft and health stability. Here we aimed to characterize the structure of gut microbiota within stable kidney graft recipients. We enrolled forty kidney transplant patients after at least three months of transplantation and compared them to eighteen healthy controls. The overall microbial community structure of the kidney transplanted group was clearly different from control subjects. We found lower relative abundances of Actinobacteria, Bacteroidetes, and Verrucomicrobia within the patient group and a higher abundance of Proteobacteria compared to the control group. Both richness and Shannon diversity indexes were significantly lower in the kidney graft recipients than in healthy controls. Post-graft period was positively correlated with the relative abundance of the Proteobacteria phylum, especially Escherichia.Shigella genus. Interestingly, only Parabacteroides was found to significantly differentiate patients that were not suffering from lifestyle diseases and those who suffer from post-graft complications. Furthermore, network analysis showed that the occurrence of lifestyle diseases was significantly linked with a higher number of negative interactions of Sutterella and Succinivibrio genera within patients. This study characterizes gut microbiome fluctuation in stable kidney transplant patients after a long post-allograft period. Analysis of fecal microbiota could be useful for nephrologists as a new clinical tool that can improve kidney allograft monitoring and outcomes.
Highlights
Increasing kidney disease and subsequent chronic kidney disease (CKD) is related to the ageing society and high morbidity due to lifestyle diseases such as diabetes, atherosclerosis, and hypertension [1]
Demographic and alpha diversity data of the kidney transplant cohort are further listed in Supplementary Table S1
We subdivided our patient cohort into subgroups according to the graft period (SG, MG, and LG) and the presence or absence of associated diseases (AD and no AD, respectively)
Summary
Increasing kidney disease and subsequent chronic kidney disease (CKD) is related to the ageing society and high morbidity due to lifestyle diseases such as diabetes, atherosclerosis, and hypertension [1]. A recent study proved that 41.3% of kidney recipients have been receiving low-value, unnecessary biopsies [6]. This evidence suggests that better diagnostic, non-invasive tools may be more effective than invasive, costly biopsies in the context of predicting kidney rejection. Tacrolimus possesses a narrow therapeutic index with sub-therapeutic levels leading to immune rejection and supra-therapeutic levels that could lead to nephrotoxicity and neurotoxicity [7] These studies suggest that nephrologists and transplant patients need better tests than creatinine and proteinuria and less invasive approaches than routine biopsies to determine when transplant patients should be investigated for rejection and immunosuppressive treatment
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