Role of gut microbiota in idiopathic nephrotic syndrome in children

Abstract

Nephrotic syndrome characterized by heavy proteinuria and edema is the most common chronic kidney disease in children. It is classified into three categories, of which the idiopathic type accounts for the vast majority of cases. As indicated by the name, the etiology of idiopathic nephrotic syndrome remains unknown though it has been suggested that impaired T cell function is involved. Recently, evidence has mounted to suggest that dysfunction in regulatory T cells plays an important role in the development of allergic disease, a recognized comorbid condition for children with idiopathic nephrotic syndrome. It is known that regulatory T cells are mainly induced by short chain fatty acids produced by gut microbiota and that children with allergy are reported to have aberrant gut microbiota. On this basis, we hypothesize that an aberrant microbiota, i.e., dysbiosis in the gut resulting in defective induction of regulatory T cells, is also involved in the etiology of idiopathic nephrotic syndrome in children. Our hypothesis can be directly tested by metagenome analysis using bacterial DNA extracted from the feces of patients with idiopathic nephrotic syndrome. Indirect evidence could be obtained by epidemiological survey, such as a comparative study of the environmental factors influencing the initial colonization of gut microbiota between patients with idiopathic nephrotic syndrome and age-matched healthy children. Factors that may disrupt this colonization include a cesarean delivery, formula feeding, excessive use of antibiotics, or the introduction of inappropriate solid foods containing a high amount of saturated fat. Based on this hypothesis, we suggest it would be clinically worthwhile to study whether administration of probiotics composed of commensal bacteria known to efficiently induce regulatory T cells in vitro could control the exacerbation or relapse of INS.