Oxalobacter sp. promotion of enteric
oxalate excretion, correlating with reductions in urinary
oxalate excretion, was previously reported in rats and mice, but the mechanistic basis for this affect has not been described. The main objective of the present study was to determine whether the apical
oxalate transport proteins, PAT1 (slc26a6) and DRA (slc26a3), are involved in mediating the Oxalobacter-induced net secretory flux across colonized mouse cecum and distal colon. We measured unidirectional and net fluxes of
oxalate across tissues removed from colonized PAT1 and DRA knockout (KO) mice and also across two double knockout (dKO) mouse models with
primary hyperoxaluria, type 1 (i.e., deficient in
alanine-glyoxylate aminotransferase; AGT KO), including PAT1/AGT dKO and DRA/AGT dKO mice compared to non-colonized mice. In addition, urinary
oxalate excretion was measured before and after the colonization procedure. The results demonstrate that Oxalobacter can induce enteric
oxalate excretion in the absence of either apical
oxalate transporter and urinary
oxalate excretion was reduced in all colonized genotypes fed a 1.5%
oxalate-supplemented diet. We conclude that there are other, as yet unidentified,
oxalate transporters involved in mediating the directional changes in
oxalate transport across the Oxalobacter-colonized mouse large intestine.