Does Sex Matter? : An in vitro Study on Sex-Simulated Microbiome in Response to a Psychotropic Drug

Abstract

Sex hormone and gut microbiota interactions are known to play a significant role in mental health and psychotropic medication responses. This study aimed to explore the sexually differentiated impact of psychotropic medication on the gut microbiome composition and diversity, with a focus on sex steroid hormones. Our findings demonstrate that psychotropic medications influence gut microbial diversity differently in male and female models. Notably, females exhibited a higher abundance of Bacteroidota and lower Firmicutes at 24h, while males displayed an opposite trend. Additionally, the α-diversity was significantly lower in females, indicating reduced microbial evenness, although no significant differences in β-diversity were observed. Psychotropic treatment resulted in increased microbial diversity in both sexes, with shifts in key taxa, such as Eubacterium coprostanoligenes and Sutterella in females, along with alterations in short-chain fatty acid production, particularly in acetate, propionate, and butyrate. These results suggest that sex hormones play an important role in modulating gut microbiome composition and their interactions with psychotropic drugs. These findings emphasize the need to consider sex-specific microbiome profiles and hormonal status when optimizing psychotropic treatments for mental health problems.