Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 310, Issue 9, Pages F857-F871Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00513.2015
Keywords
dietary fiber; resistant starch; chronic kidney disease; uremic retention solutes; gut microbiota
Categories
Funding
- T32 training award - National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000002, TL1 TR000133]
- Danish Council for Strategic Research Project [10-093526]
- USDA-ARS [2032-51530-022-00D, 6026-51000-010-05S]
- Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act
- ARS [ARS-0426492, 813598] Funding Source: Federal RePORTER
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Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.
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