The fecal microbiome and serum concentrations of indoxyl sulfate and p‐cresol sulfate in cats with chronic kidney disease

Abstract

Background Intestinal dysbiosis has been documented in humans with chronic kidney disease (CKD) and is thought to contribute to production of the uremic toxins indoxyl sulfate (IS) and p‐cresol sulfate (pCS). Characteristics of the fecal microbiome in cats with CKD and correlation to serum concentrations of uremic toxins are unknown. Objectives To characterize the fecal microbiome and measure serum IS and pCS concentrations of cats with CKD in comparison to healthy older cats. Animals Thirty client‐owned cats with CKD (International Renal Interest Society stages 2‐4) and 11 older (≥8 years) healthy control cats. Methods Prospective, cross‐sectional study. Fecal samples were analyzed by sequencing of 16S rRNA genes and Escherichia coli quantitative PCR (qPCR). Serum concentrations of IS and pCS measured using liquid chromatography tandem mass spectrometry. Results Cats with CKD had significantly decreased fecal bacterial diversity and richness. Escherichia coli qPCR showed no significant difference in bacteria count between control and CKD cats. Cats with stage 2 (P = .01) and stages 3 and 4 (P = .0006) CKD had significantly higher serum IS concentrations compared to control cats. No significant difference found between stage 2 and stages 3 and 4 CKD. The pCS concentrations were not significantly different between CKD cats and control cats. Conclusions and Clinical Importance Decreased fecal microbiome diversity and richness is associated with CKD in cats. Indoxyl sulfate concentration is significantly increased with CKD, and cats with stage 2 CKD may suffer from a similar uremic toxin burden as do cats with later stage disease.

High-throughput sequencing analysis of intestinal flora changes in ESRD and CKD patients

“…Further analyses on genus level revealed that compared with the other three groups, Bacteroides, Escherichia and Faecalibacterium was the dominant intestinal type in the PD group. Escherichia produce indoles which mainly affect the cardiovascular system and kidney functions and Faecalibacterium is one of the most abundant human fecal bacterial populations that produce butyrate, suggesting that PD treatment may increase toxins released in CKD patients [32,33]. With the accumulation of uremic toxins and activation of inflammatory reactions in CKD patients, there is a decrease in qualitative and quantitative properties of probiotics, which in turn promotes CKD progress [34,35].…”

High-throughput sequencing analysis of intestinal flora changes in elderly hemodialysis CKD patients

“…Further analyses on genus level revealed that compared with the other three groups, Bacteroides, Escherichia and Faecalibacterium was the dominant intestinal type in the PD group. Escherichia produce indoles which mainly affect the cardiovascular system and kidney functions and Faecalibacterium is one of the most abundant human fecal bacterial populations that produce butyrate, suggesting that PD treatment may increase toxins released in CKD patients [32] Gut microbiota can also affect immune system stimulation, intestinal epithelial homeostasis, vitamins B and K synthesis, gastrointestinal motility and function enhancement, nutrients absorption, drugs metabolism and SCFAs and polyamines production [4]. In our study, similar CKD and HD intestinal flora was correlated with similar expression of CRP and IL-6.…”

Preliminary evaluation of fecal fatty acid concentrations in cats with chronic kidney disease and correlation with indoxyl sulfate and p‐cresol sulfate

“…This prospective, cross‐sectional study was performed at Colorado State University Veterinary Teaching Hospital. The same population of CKD and geriatric control cats was used in a previous publication evaluating the fecal microbiome using 16S ribosomal RNA gene sequencing and serum IS and pCS concentrations . To be eligible for inclusion, CKD and control cats underwent a thorough evaluation that included a review of the past medical record, complete physical examination (including 9‐point body condition score [BCS; Nestle Purina, St. Louis, Missouri] and muscle condition score [MCS]), minimum database consisting of CBC (Advia 120 Hematology System, Siemens Healthineers, Erlangen, Germany), serum biochemistry panel (Cobas 6000, Roche Diagnostics, Indianapolis, Indiana), and urinalysis, serum total thyroxine (T4) concentration, blood pressure, fecal flotation, and urine protein:creatinine ratio (UPC; Cobas 6000, Roche Diagnostics; if urine dipstick testing detected ≥1+ protein).…”

“…Although there is limited information regarding the microbiome and its link to kidney disease in veterinary medicine, cats with CKD have fecal dysbiosis characterized by decreased fecal microbial diversity and richness based on 16S ribosomal rRNA gene sequencing . Additionally, IS is increased in cats with CKD and is associated with disease progression, and in some CKD cats, serum pCS concentrations are increased compared to healthy geriatric controls . However, to date, fecal SCFA concentrations have not been characterized in cats with CKD.…”