Cited by 308Gut microbiota and healthFood composition and propertiesDialysis and Renal Disease Management

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Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

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Kieffer, Dorothy A., Piccolo, Brian D., Vaziri, Nosratola D., Liu, Shuman, Lau, Wei L., Khazaeli, Mahyar, Nazertehrani, Sohrab, Moore, Mary E., Marco, Maria L., Martin, Roy J., Adams, Sean H.·2016·American Journal of Physiology-Renal Physiology

DOI 10.1152/ajprenal.00513.2015PMC PMC4867313

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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.

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Authors: Kieffer, D. A., Piccolo, B. D., Vaziri, N. D., Liu, S., Lau, W. L., Khazaeli, M., Nazertehrani, S., Moore, M. E., Marco, M. L., Martin, R. J., & Adams, S. H.
Affiliations: Agricultural Research Service (US)
Arkansas Children's Nutrition Center (US)
University of California, Irvine (US)
University of California, Davis (US)
Corresponding author: Adams, Sean H.
ORCID: Piccolo, Brian D.
Vaziri, Nosratola D.
Liu, Shuman
Lau, Wei L.
Khazaeli, Mahyar
Moore, Mary E.
Marco, Maria L.
Martin, Roy J.
Adams, Sean H.
Venue: American Journal of Physiology-Renal Physiology
Publisher: American Physiological Society
Published: 2016-05-01
Volume: 310
Issue: 9
Pages: F857-F871
ISSN: 1522-1466 (ISSN-L)
1931-857X
DOI: 10.1152/ajprenal.00513.2015
PMC: PMC4867313
OpenAlex: W2262540956
Cited by: 308
References: 87
Citations by year: 2026: 22 · 2025: 46 · 2024: 35 · 2023: 24 · 2022: 32 · 2021: 30 · 2020: 42 · 2019: 34 · 2018: 25 · 2017: 8 · 2016: 9
FWCI: 13.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Renal Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: HHS | NIH | National Center for Advancing Translational Sciences (NCATS) (UL1 TR000002 and linked award TL1 TR000133)
Danish Council for Strategic Research
USDA-ARS Projects (2032-51530-022-00D and 6026-51000-010-00D)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Nursing › Nutrition and Dietetics › Food composition and properties
Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Keywords: resistant starch, chronic kidney disease, gut microbiota, metabolomics, dietary fiber, adenine-induced CKD, uremic toxins, indoxyl sulfate, p-cresol, Firmicutes/Bacteroidetes ratio, cecal microbiota, microbial metabolites, renal function
MeSH terms: Gastrointestinal Microbiome, Animals, Cecum, Cresols, Diet, Dietary Fiber, Hydrogen-Ion Concentration, Kidney Function Tests, Male, Starch, Uremia, Rats, Sprague-Dawley, Rats, Renal Insufficiency, Chronic, Metabolomics

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Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

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