159. COMPARATIVE ANALYSIS OF GUT MICROBIOTA AND FUNCTIONAL PATHWAYS IN ANTIDEPRESSANT-TREATED VS. ANTIDEPRESSANT-NAïVE DEPRESSION PATIENTS AND HEALTHY CONTROLS

Abstract Background Recent research has increasingly highlighted the role of gut microbiota in various diseases, particularly in mental health, where the gut-brain axis has become a focal point. Depression, a multifaceted disorder, has been linked to gut microbiota alterations. While antidepressants (ADT) are known to affect neurotransmitters, their long-term impact on gut microbial composition is not fully understood. Aims & Objectives This study aims to explore the gut microbiota differences between antidepressant-treated depression patients, antidepressant-naïve depression patients, and healthy controls, investigating potential directional changes in microbial composition and functional pathways. This could provide new insights into the interaction between antidepressants and the gut microbiome in the context of depression treatment. Method We recruited 371 patients with depressive symptoms from hospitals in northern Taiwan, along with 151 healthy controls. Data on demographics, diet, and clinical factors were gathered through questionnaires and electronic medical records. Fecal DNA was extracted from stool samples of 522 participants, followed by 16S rRNA V3V4 gene sequencing to analyze their gut microbial profiles. Participants were grouped based on medication status (SSRI/SNRI, Others, Without ADT, and Controls) for microbial and taxa comparisons. Additionally, two indices were developed to evaluate taxa more comprehensively. Taxa correlation networks and their associations with depressive symptom severity were analyzed alongside functional pathway comparisons between groups. Results Antidepressant-naïve depression patients exhibited lower alpha diversity and distinct beta diversity compared to healthy controls. However, no significant differences were observed between patients using different types of antidepressants. At the genus level, ten differential taxa were identified between antidepressant-naïve depression patients and healthy controls, and between different antidepressant groups. Three taxa—Dialister, Leuconostoc, and Actinomyces—overlap between the comparisons, showing reversed directions of change and correlating with symptom severity. The bacterial symbiosis network was altered in antidepressant-treated and antidepressant-naïve patients compared to healthy controls. The Depression Dysbiosis Index (DDI) and Antidepressant Microbiota Index (AMI) both positively correlated with depression severity and showed significant intercorrelation. The two indices were significantly higher in both the antidepressant-treated and antidepressant-naïve patient groups. Discussion & Conclusions This study highlights significant gut microbiota changes in antidepressant-naïve depression patients, who exhibited lower alpha diversity compared to healthy controls. While no major differences were seen between antidepressant types, the overlapping taxa with reversed changes suggest a complex role of gut microbiota in depression and treatment response. Both the DDI and AMI were effective in distinguishing between antidepressant-treated and untreated patients. Further, DDI was significant. These findings underscore the importance of gut microbiota in depression and its treatment, offering potential avenues for gut-targeted therapies and further research into DDI and AMI as biomarkers.