INVESTIGATION OF GUT MICROBIOTA COMPOSITION ALTERATIONS IN DEPRESSIVE PATIENTS PRESCRIBED WITH VORTIOXETINE
Authors: Lin *Shih Kai Kevin , Chen Hsi Chung , Chen Chun Hsin , Chung Yu Chu Ella , Chen I Ming , Lu Mong Liang , Hsu Cheng Dien , Chiu Yi Hang , Wang Tsung Yang , Liu Chih Ming , Huang Ming Chyi , Wu Shu I , Kuo Po Hsiu 
Published: February 2025

Abstract

Background
Vortioxetine, a newer serotonergic antidepressant, has been used to treat adult depressive patients. It has been reported to enhance cognitive functions in patients. While the precise mechanism of action remains unknown, it’ s believed to share similarities with selective serotonin reuptake inhibitors (SSRIs). Since previous studies have indicated that SSRIs could alter gut microbial composition, and considering the correlation between depressive severity and cognitive function with gut microbiota through the gut-brain axis, we aimed to explore the disparities in gut microbial composition and cognitive function among patients treated with vortioxetine, SSRIs, and those without antidepressant treatment.

Methods
We recruited 211 patients currently experiencing depressive symptoms from hospitals in northern Taiwan. We gather their demographic, dietary, and clinical characteristics through questionnaires and electrical medical records. The Continuous Performance Test AX version (CPT-AX) assessed patients' cognitive function. Fecal DNA was extracted from 271 patients and subjected to 16S rRNA V3V4 gene sequencing to obtain their gut microbial profiles. We categorized patients into three groups for microbial and taxa comparisons. Additionally, targeted taxa correlation networks and their associations with depressive symptom severity and cognitive function indices were computed.

Results
While no significant differences in microbial diversity were observed among the groups, patients undergoing vortioxetine or SSRI treatments exhibited a decreasing trend. Compared to patients without antidepressant treatment, the vortioxetine group displayed reduced levels of four genera ( Ruminococcus, Turicibacter, Enterorhabdus, Lachnospira), and increased levels of four others ( Eggerthella, Gemella, Gordonibacter, Eubacterium). We also detected three decreased (Ruminococcus, Clostridia_UCG-014, Adlercreutzia) and one increased (Gemella) genera when comparing the vortioxetine and SSRIs groups. Notably, Eggerthella displayed a negative correlation with depression severity (r=- 0.44, p=0.04). Patients with antidepressant treatment had altered bacterial correlation compared to those without treatment. Patients taking vortioxetine exhibited slightly improved cognitive function and a more pronounced correlation trend between targeted taxa and cognitive function indices.

Conclusion
Despite vortioxetine’ s partially distinct and still not fully understood mechanism in contrast to SSRIs, our study highlights its influence on gut microbial composition, particularly taxa associated with depression or SSRIs. These findings extend previous research, emphasizing the role of microbiota in the dynamics of SSRIs and novel non-SSRI medications. This underscores the crucial involvement of gut microbiota in antidepressant treatments. Given our study's preliminary and cross-sectional nature, further research is needed to deepen our understanding of more effective therapeutic interventions.