Inhibition of urinary stone disease by a multi-species bacterial network ensures healthy oxalate homeostasis

The incidence of urinary stone disease is rapidly increasing, with oxalate being a primary constituent of approximately 80% of all kidney stones. Despite the high dietary exposure to oxalate by many individuals and its potential nephrotoxicity, mammals do not produce enzymes to metabolize this compound, instead relying in part on bacteria within the gut to reduce oxalate absorption and urinary excretion. While considerable research has focused on isolated species of oxalate-degrading bacteria, particularly those with an absolute requirement for oxalate, recent studies have pointed to broader roles for microbiota both in oxalate metabolism and inhibition of urinary stone disease. Here we examined gut microbiota from patients with and live-in individuals without urinary stone disease to determine if healthy individuals harbored a more extensive microbial network associated with oxalate metabolism. We found a gender-specific association between the gut microbiota composition and urinary stone disease. Bacteria enriched in healthy individuals largely overlapped with those that exhibited a significant, positive correlation with Oxalobacter formigenes, a species presumed to be at the center of an oxalate-metabolizing microbial network. Furthermore, differential abundance analyses identified multiple taxa known to also be stimulated by oxalate in rodent models. Interestingly, the presence of these taxa distinguished patients from healthy individuals better than either the relative abundance or colonization of O. formigenes. Thus, our work shows that bacteria stimulated by the presence of oxalate in rodents may, in addition to obligate oxalate users, play a role in the inhibition of urinary stone disease in man.