title: Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats.
abstract: 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.
authors: Obesity and Metabolism Research Unit, United States Department of Agriculture-Agricultural Research Service Western Human Nutrition Research Center, Davis, California; Graduate Group in Nutritional Biology and Department of Nutrition, University of California, Davis, California;
authors: Dorothy A
authors: DA
authors: Kieffer
authors: Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Brian D
authors: BD
authors: Piccolo
authors: Division of Nephrology, University of California, Irvine, California;
authors: Nosratola D
authors: ND
authors: Vaziri
authors: Division of Nephrology, University of California, Irvine, California;
authors: Shuman
authors: S
authors: Liu
authors: Division of Nephrology, University of California, Irvine, California;
authors: Wei L
authors: WL
authors: Lau
authors: Division of Nephrology, University of California, Irvine, California;
authors: Mahyar
authors: M
authors: Khazaeli
authors: Division of Nephrology, University of California, Irvine, California;
authors: Sohrab
authors: S
authors: Nazertehrani
authors: Department of Food Science and Technology, University of California, Davis, California; and.
authors: Mary E
authors: ME
authors: Moore
authors: Department of Food Science and Technology, University of California, Davis, California; and.
authors: Maria L
authors: ML
authors: Marco
authors: Obesity and Metabolism Research Unit, United States Department of Agriculture-Agricultural Research Service Western Human Nutrition Research Center, Davis, California;
authors: Roy J
authors: RJ
authors: Martin
authors: Graduate Group in Nutritional Biology and Department of Nutrition, University of California, Davis, California; Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas shadams@uams.edu.
authors: Sean H
authors: SH
authors: Adams
mesh_terms: D000818:Animals; D002432:Cecum / Q000382:microbiology; D003408:Cresols / Q000652:urine; D004032:Diet; D004043:Dietary Fiber / Q000494:pharmacology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007677:Kidney Function Tests; D008297:Male; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000382:microbiology* / Q000503:physiopathology; D013213:Starch / Q000494:pharmacology*; D014511:Uremia / Q000378:metabolism
chemical_list: D003408:Cresols; D004043:Dietary Fiber; C032538:4-cresol; D013213:Starch
keywords: chronic kidney disease; dietary fiber; gut microbiota; resistant starch; uremic retention solutes