Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

Abstract

Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear. We studied this using a rat model relevant to depression, where adult females with a genetic vulnerability and stressed as pups show depressive-like behaviors. Throughout pregnancy and lactation, females received the SSRI fluoxetine or vehicle. High-resolution 16S ribosomal RNA marker gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Not surprisingly, we found that pregnancy and lactation segregate in terms of fecal microbiome diversity and composition, accompanied by changes in metabolite availability. However, we also showed that fluoxetine treatment altered important features of this transition from pregnancy to lactation most clearly in previously stressed dams, with lower fecal amino acid concentrations. Amino acid concentrations, in turn, correlated negatively with the relative abundance of bacterial taxa such as Prevotella and Bacteroides. Our study demonstrates an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in a rat model relevant to depression, possibly through parallel changes in the gut microbiome. Since microbial metabolites contribute to homeostasis and development, insults to the maternal microbiome by SSRIs might have health consequences for mother and offspring.

Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection

“…Intestinal metabolite quantification. Bile acids were quantified using a Waters Acquity uPLC System with a QDa single quadrupole mass detector 99,100 . Briefly, fecal samples were suspended in methanol (5 μL/mg stool), vortexed for 1 min, and centrifuged twice at 13,000 × g for 5 min.…”

“…Quality control checks (blanks and standards) are run every eight samples. Amino acids were quantified using a Waters Acquity uPLC System with an AccQ-Tag Ultra C18 1.7 μm 2.1 × 100 mm column and a Photodiode Detector Array 100,101 . Fecal samples were homogenized in methanol (5 μL/mg stool) and centrifuged twice at 13,000 × g for 5 min.…”

“…Short chain fatty acids were quantified using a Waters Acquity uPLC System with a HSS T3 1.8 μm 2.1 × 150 mm column and a Photodiode Detector Array 99 , 100 . Fecal samples were homogenized in volatile free fatty acid mix (5 μL/mg stool, AccuStandard, New Haven, CT) and centrifuged twice (13,000 × g for 5 min).…”

Unravelling the antimicrobial action of antidepressants on gut commensal microbes

“…Nevertheless, high-dose treatments with sertraline as an adjuvant for the treatment of antibiotic-resistant E. coli infections were reported to exacerbate the pathological outcome of infection in chickens 30 . Other studies using animal models provided in vivo evidence for the antimicrobial activity of SSRIs 9 , 17 , 31 .…”

The Gut-Brain Axis and Its Role in Depression

“…The improvement of symptoms, both psychiatrically and gastrointestinal, exemplifies that mental screening in all IBS patients can provide better care. SSRIs are used in up to 10% of women for depression in pregnancy which can impact fetal brain development and the gut-brain axis [21,22]. Parallel to the impact SSRIs have on the gut-brain axis, Davey et al finds with the antipsychotic, olanzapine, results suggest that the metabolic dysfunction induced by olanzapine can be ameliorated providing new targets for antipsychotic-induced metabolic disease [23].…”