The uremia associated with chronic kidney disease (CKD) has been shown to profoundly affect the composition of the gut microbiome in people and rat models. Toxic products generated by dysbiosis may contribute to morbidity and progression of CKD.Indoxyl sulfate (IS) and p-cresol sulfate (pCS) are uremic toxins produced by colonic bacteria. The first study objective was to compare the fecal microbiome of healthy, older (> 8 years) cats (n = 11) and cats with stable CKD (IRIS stage 2-4) (n = 30). The second objective was to measure serum IS and pCS in healthy, older cats (n = 10) and compare to CKD cats (n = 28).
In this cross-sectional study, all cats had a complete blood count, chemistry panel, total T4, urinalysis, blood pressure, and fecal flotation at enrollment. CKD cats had creatinine > 1.6 mg/dL and USG < 1.035 or an elevated creatinine at at least two time points in addition to an elevated SDMA > 14 ug/dL. Healthy cats were > 8 years of age and had a creatinine < 1.6 mg/dL and USG > 1.035. Exclusion criteria were a history of antibiotic, probiotic, or antacid administration < 6 weeks prior to enrollment or a history of uncontrolled hyperthyroidism and known or suspect gastrointestinal disease. A fresh fecal sample was collected by the owner and placed on ice until frozen within 24 hours of collection. For microbiome analysis, extracted fecal DNA was used for Illumina sequencing of the bacterial 16S rRNA gene. Differences in the proportions of bacterial taxa between the species were evaluated using Kruskal-Wallis tests. Serum IS and pCS were measured using LC/MS/MS. Median values between CKD cats and healthy control cats were compared using the Mann Whitney test and groups were compared using Kruskal Wallis with Dunn’s post hoc analysis.
The number of observed species and Chao 1 were significantly decreased in CKD cats when compared to healthy cats, p = 0.026 and p = 0.0284 respectively. The Shannon diversity index was decreased in CKD cats compared to healthy cats, however it was not significant (p = 0.0617). There was no significant difference in overall clustering of microbial communities between CKD cats and healthy cats (p = 0.72). However, when individual bacterial groups were analyzed based on LDA effect size (LEfSe) several bacterial taxa were identified as being significantly different among the groups. When comparing healthy cats to CKD cats, CKD cats had significantly decreased bacterial populations belonging to the genera Holdemania, Adlercreutzia, Eubacterium, Slackia, and Mogibacterium. No significant differences in the functional potential of the microbiota were found between CKD cats and healthy cats after correcting for multiple comparisons. IS levels were found to be significantly higher in CKD cats compared to healthy cats (p < 0.0001). Healthy control cats had significantly lower IS levels compared to stage 2 (p = 0.01) and stage 3 & 4 (p = 0.0006) CKD cats. No significant difference was found between Stage 2 and Stage 3 & 4 CKD cat groups. pCS levels were not significantly different between CKD and healthy controls.
In conclusion, feline CKD is associated with decreased diversity of the gut microbiome. IS is significantly elevated in feline CKD and merits exploration as a potential therapeutic target. Additionally, IRIS stage 2 cats may suffer from a similar uremic toxin burden as cats with later stage disease. Additional work is needed to further understand the interplay between the fecal microbiome and uremic toxins.
Smal Animal Internal Medicine Resident
Colorado State University, College of Veterinary Medicine
I graduated from Washington State University with a degree in Doctor of Veterinary Medicine in 2013. I finished a rotating small animal intership at Wheat Ridge Veterinary Specialists in Wheat Ridge, Colorado in 2014 and was then accepted a research fellowship at Colorado State University (CSU) with Dr. Michael Lappin. My research during my fellowship focused on feline medicine including feline herpesvirus-1, the effect of probiotics for treatment of antibiotic-induced dysbiosis, and developing a reserach model for chronic kidney disease. I am currently finishing a small animal internal medicine residency program at CSU and I will be graduating in July. I plan on continuing my research in a phD program at CSU on feline chronic kidney with focus on disease pathogenesis and treatment.
Friday, June 15
2:00 PM – 2:15 PM
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