#2819 The association between oral proteome and microbiome in kidney transplant recipients: 24-months prospective study

Abstract

Abstract Background and Aims Recent evidence observed changes in saliva composition and an oral dysbiosis in end-stage renal disease (ESRD) patients. Despite of that, the relationship between oral microbiome and oral peptidome in kidney transplant recipients (KTR) is still unexplored. Therefore, the aim of this study is to investigate the interplay between oral microbiome and oral peptidome in KTR from live kidney donors (LKD) and to analyze their relevance on the recovery of renal function. Method This prospective study enrolled 11 adult KTR/LKD pairs to whom saliva was collected before organ transplant/donation (T0) and at 6 (T6), 12 (T12), and 24 (T24) months after (dropout rate up to 45% at T24). Saliva microbiome was evaluated by throughput sequencing (16SrRNA gene) and low-molecular weight salivary proteome by LC-MS/MS analysis. Results The glomerular filtration rate (GFR) of KTR recover to normal levels after transplant. Oral microbiome of ESRD differ significantly from healthy donors (T0; p = 0.04), however these differences fade away progressively post-transplant, presenting only a slight difference at T6 (p = 0.046) but no differences at T12 and T24. Also, 21 proteins were found dysregulated in ESRD and after protein-protein interaction analysis were organized into two functional clusters: one mainly composed by cysteine protease inhibitors, and another mainly composed by metabolism-related enzymes (lactate dehydrogenase, catalase, and arginase-1). Almost all differences between LKD and KTR became elusive at 6 months. It was found an inverse correlation between Streptococcus and peptidyl-prolyl-cis-trans-isomerase-A, a protein with a strong chemotactic effect on leukocytes, and a positive correlation between Bergeyellaand cystatin-D (CST5), a cysteine proteases-protective protein. The remaining secreted cystatins (CST1/2/4), but not CST5 were found significantly correlated with GFR, suggesting that renal function recovery is paralleled related to an increase in oral cystatins. Also, an inverse relationship between Bergeyella and GFR suggests that the renal function recovery has implications in the composition of oral microbiota. Conclusion This study may provide relevant clues about the oral cavity-kidney axis dynamics and pinpoint potential markers of renal function impairment and/or recovery in KTR.