Uraemia does not induce significant dysbiotic change in the gut microbiota of experimental animals

Rodent models of kidney disease offer a way of investigating the effects of uraemia on the gut microbiota in the absence of confounding factors relevant in humans studies, such as the effects of diet or medications. Previous rodent studies have described clear effects of uraemia on the gut microbiota, which have sometimes been termed uraemic dysbiosis, however, all have been based on single cohorts of animals. Here, we present next-generation sequencing data from the intestinal microbiota of rats and mice from five separate shipment cohorts. We show that species and cohort effects strongly outweigh any effect of uraemia on gut bacterial communities, and on the level of individual cohorts, fail to demonstrate any common or reproducible effect of uraemia on the gut microbiome. We use 1H NMH spectroscopy to assess the 24 hour urinary excretion of a number of common bacterial metabolites, and show that cohort effects again outweigh the effect of uraemia in all cases, although we suggest that production of the uremic toxin indoxyl sulphate and of several of the short chain fatty acids might be modified in uraemia. We conclude that effects of uraemia on the gut microbiome seen in individual cohorts of animals do not easily generalise to other groups. Further investigation of the functional capacity of the microbiome, and study of whether this can be manipulated to improve outcomes in kidney disease may prove more productive than trying to define a common pattern of uremic dysbiosis.