Lactobacillus acidophilus LA85 reverses experimental diabetic sensory neuropathy by restoring redox homeostasis in the spinal cord.

Abstract

Lactobacillus acidophilus (LA) ingestion has been previously shown to be beneficial for glycemic control and pain management, but not in diabetic neuropathy (DN). The present work was designed to evaluate the therapeutic potential of daily treatment with Lactobacillus acidophilus LA85 (LA85) strain in a model of streptozotocin (STZ)-induced painful DN in mice and characterize its mechanisms of action. Male C57BL/6 mice received a daily intraperitoneal administration of STZ (60 mg/kg, 3 days). After the establishment of sensory neuropathy, mice were daily treated with LA85 (1.0 × 107 or 1.0 × 109 CFU), vehicle, or gabapentin (isolated or associated with LA85) for 28 days. Nociceptive thresholds were assessed using von Frey and Hargreaves tests. Motor performance was evaluated in the rota-rod test. Glycaemic measurement was determined before and after induction in four different times. Gene expression profile, cytokine levels, and oxidative stress biomarkers in the spinal cord were evaluated by real-time PCR, ELISA, and biochemical assays, respectively. STZ-induced mice showed persistent hyperglycaemia and compatible behavioural signs of sensory neuropathy, such as mechanical allodynia and thermal hypoalgesia. Treatment with LA85, especially at 1.0 × 109 CFU, significantly reduced the neuropathy signs. No LA85-induced motor impairment was evidenced in the rota-rod test. LA85 treatment reduced levels of interleukin-1β, malondialdehyde, and nitrite, and modulated oxidative stress biomarkers in the spinal cord of diabetic mice. The long-lasting antinociceptive effect induced by Lactobacillus acidophilus LA85 during diabetic neuropathy may be associated with reestablishment of redox and immune homeostasis in the spinal cord.