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. Conclusion: 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.
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The abundance of Lactobacillus is decreased in chronic kidney disease.
“As the abundance of Lactobacillus is decreased in CKD101,106”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [106]
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The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
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- Authors
- Kikuchi, M., Ueno, M., Itoh, Y., Suda, W., & Hattori, M.
- Affiliations
- Kureha (Japan) (JP)
- The University of Tokyo (JP)
- Venue
- Nephron
- Publisher
- S. Karger AG
- Published
- 2016-10-05
- Volume
- 135
- Issue
- 1
- Pages
- 51-60
- ISSN
- 1660-8151 (ISSN-L)
- 2235-3186
- OpenAlex
- W2528122499
- Cited by
- 82
- References
- 32
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 11 · 2023: 14 · 2022: 13 · 2021: 4 · 2020: 13 · 2019: 11 · 2018: 9 · 2017: 3
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Nephron journals/Nephron journals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- uremic toxins, gut microbiota, chronic kidney disease, AST-120, carbon adsorbents, indoxyl sulfate, phenyl sulfate, cecal microbiota, Clostridia, Bacteroidia, tryptophanase, tyrosine phenol-lyase
- MeSH terms
- Gastrointestinal Microbiome, Animals, Clostridium, Disease Models, Animal, Humans, Indican, Male, RNA, Bacterial, RNA, Ribosomal, 16S, Sulfuric Acid Esters, Toxins, Biological, Rats, Sprague-Dawley, Bacteroidetes, Rats, Renal Insufficiency, Chronic
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