Can Changing Gut Flora Reduce Medication-Induced Metabolic Effects?

Joel Yager, MD

A gut-sterilizing antibiotic cocktail prevents olanzapine-induced weight gain in rats.

In animals and humans, differences in gut microbial flora are associated with variations in body weight and fat deposition, and transplants of gut microbes from lean humans have decreased obesity in mice (Science 2013; 341:1241214). Because olanzapine alters fecal microbiota in rats, gut flora might be related to olanzapine's metabolic effects. These researchers investigated whether administering antibiotics to change gut microbial flora might minimize olanzapine's obesogenic effects.

Weight-matched female rats received an antibiotic cocktail of neomycin, metronidazole, and polymyxin (a mixture that effectively sterilizes the gut) or neutral vehicle for 5 days and then began coadministered olanzapine or vehicle for 21 days. Olanzapine alone was associated with increases in weight gain, plasma free fatty acids, and peri-uterine fat deposits. It also changed microbiota profiles by proportionally shifting populations of two bacterial phyla in directions previously associated with obesity in animals and humans. Coadministering antibiotics did not alter olanzapine-associated increased food intake or reduced locomotion. But, antibiotic treatment shifted microbiota profiles in the opposite direction of those induced by olanzapine alone, reduced olanzapine-induced weight gain, and prevented increases in plasma free fatty acids and peri-uterine fat deposits. However, antibiotic treatment did not prevent olanzapine-induced insulin resistance.

Citation(s):

Davey KJ et al. Antipsychotics and the gut microbiome: Olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatr 2013 Oct 1; 3:e309.