ROLE OF HUMAN MICROBIOME AND VIROME IN THE PATHOGENESIS AND DISEASE COURSE OF IDIOPATHIC NEPHROTIC SYNDROME IN CHILDREN

Abstract

Pediatric idiopathic nephrotic syndrome (INS) is characterized by a triad of edema, hypoalbuminemia and proteinuria. The main cause of the disease remains unknown, but its pathogenesis is thought to involve inherited structural abnormalities of the podocytes, immune dysregulation, microbial infections and other environmental factors. Microbial infection remains the leading cause of comorbidity and dealth in children with INS. This study aims to close the gap in the current understanding of the etiology and pathophysiology of INS in children, by characterizing the gut and urinary metagenome and virome. Stool and urine samples were collected from 73 INS patients and 40 healthy controls attending Sidra Medicine. To characterize the composition of the metagenome, samples were processed using whole genome metagenomics sequencing by shotgun approach that revealed the compostion of the bacteriome and mycobiome. To assess the virome compostion, enrichment of the viral particles was performed before processing the samples. Our data showed that lower microbial richness was observed in the gut bacteriome of INS patients compared to healthy controls, in contrast an increased richness in the gut mycobiome was observed in INS patients. Specific bacterial species in the gut, showed a strong predictive value of disease onset and relapse, when we applied the random forest prediction model, indicating that this bacterial signature may be used to predict disease onset and progression once confirmed in future studies. Enriched urinary bacteriome and mycobiome were also observed in INS patients when compared to healthy controls. Significant differences were noted when we compared the urinary and gut virome in INS patients and controls, suggesting a central role of bacteriophages in the disease pathogenesis and progression. Our data suggest that, in INS patients, microbial differences may play a role in the pathogenesis and disease course. Our study is a step forward for large study cohorts, and deeper investigations aiming to look at the inter-kingdom interactions of bacteria, viruses, and fungi in the context of health and disease, are still warranted.

Date of Award	2022
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences