title: Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.
authors.affiliation: Children's Hospital, New Orleans, LA, USA.|Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Crespo-Salgado
authors.affiliation: Children's Hospital, New Orleans, LA, USA.|Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: V Matti
authors.initials: VM
authors.lastname: Vehaskari
authors.affiliation: Children's Hospital, New Orleans, LA, USA.|Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Tyrus
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Children's Hospital, New Orleans, LA, USA.|Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ferris
authors.affiliation: Xavier University of Louisiana, New Orleans, LA, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Xavier University of Louisiana, New Orleans, LA, USA.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Blanchard
authors.affiliation: Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Taylor
authors.affiliation: University at Buffalo, Buffalo, NY, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Kallash
authors.affiliation: Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Greenbaum
authors.affiliation: Children's Hospital, New Orleans, LA, USA. davile@lsuhsc.edu.|Louisiana State University Health Sciences Center, New Orleans, LA, USA. davile@lsuhsc.edu.
authors.forename: Diego H
authors.initials: DH
authors.lastname: Aviles
mesh_terms: D039903:Actinobacteria / Q000302:isolation & purification; D000293:Adolescent; D058491:Bacterial Load; D041963:Bacteroidetes / Q000302:isolation & purification; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003408:Cresols / Q000097:blood*; D005243:Feces / Q000382:microbiology; D005260:Female; D000068536:Bacillota / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D007200:Indican / Q000097:blood*; D007422:Intestines / Q000382:microbiology; D007676:Kidney Failure, Chronic / Q000382:microbiology*; D016030:Kidney Transplantation; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010530:Peritoneal Dialysis; D020560:Proteobacteria / Q000302:isolation & purification; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013463:Sulfuric Acid Esters / Q000097:blood*; D014511:Uremia / Q000097:blood*; D061327:Verrucomicrobia / Q000302:isolation & purification
chemical_list: D003408:Cresols; D012336:RNA, Ribosomal, 16S; D013463:Sulfuric Acid Esters; D019344:Lactic Acid; C408690:4-cresol sulfate; D002097:C-Reactive Protein; D007200:Indican
keywords: Children; End-stage renal disease; Inflammation; Intestinal microbiota; Pyrosequencing; Uremic toxins