The Probiotic Mixture VSL#3 Reverses Olanzapine-Induced Metabolic Dysfunction in Mice.

Abstract

Atypical antipsychotic drugs (AAPDs) such as olanzapine (OLZ) are associated with serious metabolic adverse effects such as weight gain, visceral fat accretion, glucose intolerance, and lipid abnormalities. Compelling evidence suggests that the gut microbiota is known to regulate metabolic homeostasis and therefore microbiota-modulating strategies such as probiotics may serve as an excellent approach for treating metabolic adverse effects associated with atypical antipsychotic drugs (AAPDs). The therapeutic potential of VSL#3 (20 × 10 CFU/day), in reversing olanzapine-induced metabolic dysfunction, was assessed. VSL#3 administration led to attenuation of OLZ-induced body weight gain, uterine fat deposition, impaired glucose tolerance, and insulin resistance. Moreover olanzapine treatment also decreased inflammatory markers, abolished oxidative stress in the vWAT, and prevented shifts in gut microbiota abundance levels. These results indicate that VSL#3 via its ability to manipulate the gut microbiome confers beneficial metabolic effects and may, therefore, represent a novel therapeutic approach for reversing antipsychotic-induced metabolic dysfunction.