title: Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD.
abstract: BACKGROUND
  Intestinal microbiome constitutes a symbiotic ecosystem that is essential for health, and changes in its composition/function cause various illnesses. Biochemical milieu shapes the structure and function of the microbiome. Recently, we found marked differences in the abundance of numerous bacterial taxa between ESRD and healthy individuals. Influx of urea and uric acid and dietary restriction of fruits and vegetables to prevent hyperkalemia alter ESRD patients' intestinal milieu. We hypothesized that relative abundances of bacteria possessing urease, uricase, and p-cresol- and indole-producing enzymes is increased, while abundance of bacteria containing enzymes converting dietary fiber to short-chain fatty acids (SCFA) is reduced in ESRD.
  
  
  METHODS
  Reference sets of bacteria containing genes of interest were compiled to family, and sets of intestinal bacterial families showing differential abundances between 12 healthy and 24 ESRD individuals enrolled in our original study were compiled. Overlap between sets was assessed using hypergeometric distribution tests.
  
  
  RESULTS
  Among 19 microbial families that were dominant in ESRD patients, 12 possessed urease, 5 possessed uricase, and 4 possessed indole and p-cresol-forming enzymes. Among 4 microbial families that were diminished in ESRD patients, 2 possessed butyrate-forming enzymes. Probabilities of these overlapping distributions were <0.05.
  
  
  CONCLUSIONS
  ESRD patients exhibited significant expansion of bacterial families possessing urease, uricase, and indole and p-cresol forming enzymes, and contraction of families possessing butyrate-forming enzymes. Given the deleterious effects of indoxyl sulfate, p-cresol sulfate, and urea-derived ammonia, and beneficial actions of SCFA, these changes in intestinal microbial metabolism contribute to uremic toxicity and inflammation.
authors.affiliation: Center for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, California.
authors.forename: Jakk
authors.initials: J
authors.lastname: Wong
authors.affiliation: Center for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, California.
authors.forename: Yvette M
authors.initials: YM
authors.lastname: Piceno
authors.affiliation: Second Genome, San Bruno, California.
authors.forename: Todd Z
authors.initials: TZ
authors.lastname: DeSantis
authors.affiliation: Division of Nephrology and Hypertension, University of California Irvine, Irvine, California.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Pahl
authors.affiliation: Center for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, California.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Andersen
authors.affiliation: Division of Nephrology and Hypertension, University of California Irvine, Irvine, California.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
mesh_terms: D000328:Adult; D000368:Aged; D000641:Ammonia / Q000737:chemistry; D003408:Cresols / Q000737:chemistry*; D004032:Diet; D005232:Fatty Acids, Volatile / Q000737:chemistry*; D005260:Female; D006801:Humans; D007200:Indican / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D007249:Inflammation; D007422:Intestines / Q000382:microbiology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D013463:Sulfuric Acid Esters / Q000737:chemistry; D014503:Urate Oxidase / Q000096:biosynthesis*; D014508:Urea / Q000737:chemistry; D014510:Urease / Q000096:biosynthesis*
chemical_list: D003408:Cresols; D005232:Fatty Acids, Volatile; D007211:Indoles; D013463:Sulfuric Acid Esters; C032538:4-cresol; C408690:4-cresol sulfate; D000641:Ammonia; D014508:Urea; D014503:Urate Oxidase; D014510:Urease; D007200:Indican