title: Uremic Toxin-Producing Gut Microbiota in Rats with Chronic Kidney Disease.
abstract: BACKGROUND
  In patients with chronic kidney disease (CKD), many metabolites of gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of bacteria producing UTs are rarely discussed.
  
  
  METHODS
  We analyzed UT production and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120, a spherical carbon adsorbent, was administrated to evaluate how the precursors of UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid chromatography/electrospray ionization-tandem mass spectrometry. Gut microbiota were analyzed using 454-pyrosequencing of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering and UniFrac analysis were performed to compare gut microbiota among the groups.
  
  
  RESULTS
  Serum and urine levels of indoxyl sulfate and phenyl sulfate were higher in CKD versus control rats (p < 0.05). AST-120 administration decreased UT production (p < 0.01) and changed overall gut microbiota composition in CKD rats. UT urinary excretion and gut microbiota composition changed in cecectomized rats, with the relative abundance of Clostridia- and Bacteroidia-affiliated species being significantly reduced (p < 0.01). We identified candidate indole- and phenol-producing intestinal microbiota, 3 Clostridia, and 2 Bacteroidia. These OTUs have a tryptophanase/tyrosine phenol-lyase gene in the closest sequenced genome out of the OTUs declined following cecectomy.
  
  
  CONCLUSIONS
  Our data suggest that UT production is correlated with a subset of indigenous gut microbiota. However, UT may be induced by other non-symbiotic microbiota that are influenced by factors other than microbiota populations. The relationship between specific microbiota and UTs in patients requires further clarification.
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Tokyo, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Mariko
authors.initials: M
authors.lastname: Ueno
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Itoh
authors.forename: Wataru
authors.initials: W
authors.lastname: Suda
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
mesh_terms: D000818:Animals; D041963:Bacteroidetes / Q000235:genetics / Q000302:isolation & purification; D003013:Clostridium / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007200:Indican / Q000096:biosynthesis; D008297:Male; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000382:microbiology*; D013463:Sulfuric Acid Esters / Q000378:metabolism; D014118:Toxins, Biological / Q000096:biosynthesis* / Q000652:urine
chemical_list: D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological; C026865:uremia middle molecule toxins; C025208:phenylsulfate; D007200:Indican