Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study

• Authors: Janice Crespo-Salgado, Children’s Hospital, New Orleans; V. Matti Vehaskari, Children’s Hospital, New Orleans; Tyrus Stewart, Children’s Hospital, New Orleans; Michael Ferris, Children’s Hospital, New Orleans; Qiang Zhang, Xavier University of Louisiana; Guangdi Wang, Xavier University of Louisiana; Eugene E. Blanchard, Louisiana State University; Christopher M. Taylor, Louisiana State University; Mahmoud Kallash, University at Buffalo; Larry Greenbaum, Emory University; Diego H. Aviles, Children’s Hospital, New Orleans
• Journal Title: Microbiome
• Volume: Volume 4, Number 1
• Publisher: BioMed Central | 2016-09-17, Pages 50-50
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s40168-016-0195-9
• Subjects: Biology, Microbiology; Health Sciences, General; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Microbiology; End-stage renal disease; Children; Intestinal microbiota; Uremic toxins; Inflammation; Pyrosequencing; CHRONIC KIDNEY-DISEASE; P-CRESYL SULFATE; GUT BACTERIAL TRANSLOCATION; BOUND UREMIC TOXINS; INDOXYL SULFATE; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS; EARLY-LIFE; MICROINFLAMMATION

Abstract

Background: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. Methods: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured. Results: Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P = 0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P = 0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P = 0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic = 0.2656, P = 0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P < 0.0001 and P < 0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria. Conclusions: Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.