Targeting Bifidobacterium animalis alleviates high-fluoride exposure-induced kidney injury in mice

In areas with high fluoride concentrations in drinking water, residents may consume excessive fluoride, which may increase the risk of renal impairment. Although accumulating evidence suggests that probiotics may exert renoprotective effects, support for probiotic interventions against fluoride-associated renal injury remains limited, and the effects appear to be strain dependent. In a prolonged exposure model, mice received sodium fluoride in drinking water (25 or 50 ppm) for 56 weeks, after which renal function was assessed and metagenomic profiling was performed. Mice exposed to varying fluoride concentrations developed renal injury, and the relative abundance of Bifidobacterium animalis was significantly correlated with markers of renal function. A short-term fluoride-exposure model (sodium fluoride, 24 mg/kg/day for 8 weeks, by gavage) was used to evaluate the renal protective effect of Bifidobacterium animalis GY007. Supplementation with GY007 significantly reduced renal injury markers, including β2-microglobulin (β2-MG) and lipocalin 2 (LCN2). GY007 reduced pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), increased anti-inflammatory interleukin-10 (IL-10), and alleviated oxidative stress. Transmission electron microscopy (TEM) analysis indicated that GY007 improved mitochondrial morphology in damaged renal tissue. Further analyses showed that GY007 improved mitochondrial membrane potential, attenuated the upregulation of dynamin-related protein 1 (Drp1) and fission 1 (Fis1), and normalized altered mitochondrial DNA (mtDNA) copy number. The mRNA levels of mtDNA-encoded genes (mtND3, mtCO2, and mtcyb) and the nuclear-encoded gene Sdhb were altered. Kidney metabolomic analysis revealed metabolic alterations associated with GY007 supplementation in fluoride-exposed mice, identifying eight significantly altered metabolites. This study provides evidence supporting the development of probiotic interventions to mitigate fluoride-associated renal injury in settings with elevated fluoride concentrations in drinking water.