Gut microbiota and oxalate homeostasis

Abstract

This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence.

Keywords: Bifidobacterium sp.; Oxalobacter sp.; caecum; distal colon; hyperoxalemia; hyperoxaluria; intestinal oxalate transport; lactobacillus sp.; small intestine; urinary oxalate excretion; urolithiasis.

Figure 1

Comparison of 24-h urinary oxalate excretion in AGT knockout mice before (n=12) and 12 days after oral gavage with either HC-1 alone (n=6) or a combined inoculum of HC-1 and B. animalis (n=6). These mice were being fed a diet supplemented with 1.5% oxalate during the study period. Reductions in urinary excretion did not reach a level of significance using an ANOVA: P≤0.05.

Figure 2

Unidirectional fluxes of oxalate (J, pmoles·cm⁻²·h⁻¹) measured across the isolated, short-circuited distal ileum, caecum, and distal colon removed from AGT knockout mice either colonized with HC-1 alone or with a combined inoculum of HC-1 and B. animalis (n=6 tissue pairs in each group) fed a diet supplemented with 1.5% oxalate for 12 days. Transepithelial conductance (G_T) and short circuit current (I_sc) were not statistically different between the two animal groups (see Table 1). D-lleum, distal ileum; D-colon, distal colon.

Figure 3

Unidirectional fluxes of oxalate (J, pmoles·cm⁻²·h⁻¹) measured across the isolated, short-circuited distal colon removed from C57BL/6 wild type mice colonized with L. acidophilus, or L. gasseri, compared to control mice not colonized (n=6 in each group) and fed a diet supplemented with 1.5% oxalate for 12 days. Transepithelial conductance (G_T) and short circuit current (I_sc) recordings were not statistically different among the three animal groups (see Table 2).