The Gut Microbiome in Autosomal Dominant Polycystic Kidney Disease: A Cross-Sectional Study.

Abstract

Background: Changes in gut microbiota signatures have been associated with chronic kidney disease and nephrolithiasis and may thus be a factor explaining variability of outcome in ADPKD. We aimed to characterize the intestinal microbiome in a cross-sectional study of patients with ADPKD and to explore the potential impact of microbiome signatures on PKD disease progression.

Methods: This observational cross-sectional pilot study recruited 25 patients from the AD(H)PKD patient cohort and 12 healthy, age- and sex matched control subjects. The gut microbiome was analyzed by 16S rRNA gene profiling of stool samples. Bacteria-derived serum uremic toxins were measured using liquid chromatography coupled to tandem mass spectrometry. Microbiome data was correlated with age, kidney function, and markers of PKD disease progression like Mayo classification and arterial hypertension <35 years of age.

Results: Patients with ADPKD displayed a significantly decreased abundance of Actinobacteria including probiotic Bifidobacteriaceae and significantly increased abundance of Enterobacteriaceae. Those findings were independent of kidney function. Most notably, Streptococcaceae were significantly overrepresented in patients with Mayo Classes 1D and 1E compared to 1A-1C. Additionally, early onset of hypertension (< 35 years of age) was associated with an increased abundance of Proteobacteria and a decreased abundance of Tannerelleaceae. Furthermore, patients with ADPKD revealed an increased abundance of Peptococcaceae with increasing age and declining kidney function. Finally, serum uremic toxin levels were significantly increased in patients with ADPKD, highly correlating with eGFR.

Conclusions: This pilot study suggests relevant changes in gut microbiota signatures of patients with ADPKD which might be associated with rapid disease progression. These findings indicate that composition of the gut microbiota could potentially contribute to disease progression of ADPKD and the individual disease variability. Further investigation is warranted to assess the gut microbiota as a potential therapeutic target in ADPKD.