Perinatal citalopram exposure alters the gut composition and microbial metabolic profiles of Sprague-Dawley rat dams and female offspring but not male offspring

Plain english summary Selective serotonin reuptake inhibitors (SSRIs) like citalopram are commonly prescribed to pregnant women, yet their effects on the developing gut microbiome of offspring are not well understood. This study aimed to examine how citalopram exposure during pregnancy and nursing impacts gut bacteria and their metabolic influence both maternally and in offspring, with a focus on sex differences. Using cutting-edge metagenomic sequencing, we analyzed fecal samples from rat dams treated with citalopram, as well as from their male and female pups. We found that citalopram exposure caused clear shifts in the gut microbiome and microbial metabolism in the dams and female offspring, but not in male offspring. Dams and female offspring showed changes in the diversity and composition of gut bacteria, as well as in the metabolic functions those microbes perform. Male offspring showed minimal changes, suggesting that they are less susceptible to SSRI-related microbial alterations. Importantly, the gut microbial and metabolic profiles of female offspring resembled those of the mothers more closely than those of male offspring. These results highlight that exposure to SSRIs during development can lead to long-lasting and sex-specific changes in the gut microbiome. Understanding how SSRIs impact the gut ecosystem is important for assessing the full spectrum of their effects during pregnancy and how that effects the subsequent generation. This research emphasizes the need to consider sex differences when evaluating the safety and long-term outcomes of antidepressant use during pregnancy.