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 × 109 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.
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The authors would like to acknowledge Prof Kanwaljit Chopra, Dr Mahendra Bishnoi, and Dr Kanti Kiran Kondepudi for their guidance and support.
Raskind MA, Burke BL, Crites NJ, Tapp AM, Rasmussen DD (2007) Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats. Neuropsychopharmacology 32:284–288CrossRefGoogle Scholar
Nasrallah H (2008) Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 13:27–35CrossRefGoogle Scholar
Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen H-L, Rickels K (2013) Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes 62:3232–3240CrossRefGoogle Scholar
Davey K, Cotter P, O’sullivan O, Crispie F, Dinan T, Cryan J, O’mahony S (2013) Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 3:e309CrossRefGoogle Scholar
Deol P, Evans JR, Dhahbi J, Chellappa K, Han DS, Spindler S, Sladek FM (2015) Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver. PLoS One 10:e0132672CrossRefGoogle Scholar
Wills E (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667CrossRefGoogle Scholar
Dkhar P, Sharma R (2013) Attenuation of age-related increase of protein carbonylation in the liver of mice by melatonin and curcumin. Mol Cell Biochem 380:153–160CrossRefGoogle Scholar
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138CrossRefGoogle Scholar