Lactobacillus acidophilus abolishes oxalate-mediated renal epithelial barrier disruption and calcium oxalate monohydrate crystal adhesion to renal epithelial cells

It is generally known that kidney stone disease (KSD) is associated with alterations in urinary microbiome, but the roles of the urinary microbiome in KSD pathogenesis remain unclear. This study addressed the impact of Lactobacillus acidophilus (a commensal bacterium found in normal urine) on renal epithelial integrity, calcium oxalate monohydrate (COM) crystal-cell adhesion, expression of membrane receptors of COM crystals, and oxalate degradation under oxalate-induced stress (a known inducer of KSD). Inner medullary collecting duct cells (mIMCD-3) were cultured for 24 h under control or oxalate-induced (by 0.6 mM sodium oxalate; NaOx) conditions without or with L. acidophilus (at 1 × 10 3 colony-forming unit (CFU)/ml) co-incubation. NaOx reduced transepithelial resistance (TER) of the mIMCD-3 monolayer and downregulated ZO-1, a tight junction (TJ) protein. Additionally, NaOx enhanced the COM crystal-binding capability of mIMCD-3 cells by upregulating a COM crystal receptor, annexin A2, on cell membranes. Such harmful effects of NaOx were abolished when mIMCD-3 cells were co-cultured with L. acidophilus . Moreover, culturing L. acidophilus in artificial urine (AU) supplemented with NaOx for 24 h revealed that the oxalate level in AU decreased, suggesting the oxalate-degrading activity of the bacterium in an AU environment. L. acidophilus prevented oxalate-mediated renal epithelial barrier disruption and COM crystal adhesion to renal epithelial cells by preserving ZO-1 and annexin A2 expression at their basal levels, at least in part, via its oxalate-degrading property. Not applicable (This is not a clinical trial).