Fecal microbiota analysis of polycystic kidney disease patients according to renal function: A pilot study

Abstract

Gut bacterial microbiota is altered in patients with advanced renal disease and those on dialysis. However, it is not clear yet what bacterial composition changes are due to the renal insufficiency per se, and what are in result of the accompanying interventions and comorbid conditions. Most studies analyzed diabetic nephropathy, hypertensive nephropathy, and glomerulonephritis patients which might have directly influenced the microbiome regardless of alterations in renal function. We present in this report changes in gut bacterial microbiota in a highly selected group of patients with strict inclusion criteria to eliminate the effects of the confounding factors on the microbiome composition. We conducted multiple analysis approaches according to participants’ renal function to further understand microbiome alteration in different degrees of renal insufficiency. An interesting group of bacteria showed a step-wise change in relative abundance in response to the three groups’ analysis. These bacteria either decreased or increased from mild, moderate to severe renal insufficiency indicating strong and direct effects of the uremic milieu on its relative abundance. We also ran a sensitivity analysis that took into account an assembly of the significant taxa observed in an approach to investigate whether these taxa can fully explain the separation noted between the groups. We determined the projected metabolic pathways altered according to the gut microbiota composition changes. This report not only delineates with a higher certainty the effects of alteration in renal function on the microbiome, but also explores the possible role of dysbiosis on comorbid conditions through alterations in the projected metabolic pathways. Impact statement The heterogeneity of the renal disease, therapeutic interventions, and the original cause of the renal failure, all directly affect the microbiota. We delineate in this report the direct effect of decreased renal function on the bacterial composition following stringent criteria to eliminate the possibilities of other confounding factors and dissect the direct effects of the uremic milieu. We analyzed the microbiome following three different approaches to further evaluate the effects of mild, moderate and advanced renal insufficiency on the microbiome. We also present here a detailed functional analysis of the projected altered pathways secondary to changes in the microbiome composition.