Antidepressants May Restore Anti-Inflammatory Bacteria Diminished by Depression in Parkinson's Patients

Abstract

Depression is highly prevalent among Parkinson’s disease (PD) patients. The gut-brain axis and gut microbiota dysbiosis are associated with both PD and depression. Antidepressants, commonly prescribed for treatment, are known to alter gut microbial composition. However, the relationship between these microbial changes and depression outcomes in PD patients remains poorly understood. This study investigated whether gut microbiota mediates the efficacy of antidepressants in PD patients. We hypothesized that antidepressant use restores the gut microbiome to a non-depressive state, contributing to improved depression outcomes. Using the Cirstea et al. (2020) dataset, we analyzed gut microbiota profiles from 66 PD patients considering depression severity and antidepressant use. Raw sequencing data was processed in QIIME2 to generate amplicon sequence variants (ASVs) and taxonomically classify them using the SILVA database. Alpha and beta diversity metrics were calculated to assess microbial diversity, core microbiome analysis was conducted, and differential abundance analysis was performed. Diversity metrics revealed no significant associations with depression severity or antidepressant use. However, core microbiome analysis indicated that microbial profiles in high depression patients using antidepressants were 20% more similar to low depression patients. Furthermore, our study also revealed that antidepressant use restored two anti-inflammatory genera and reduced one pro-inflammatory genus, indicating a potential anti-inflammatory and restorative effect on the gut microbiome. These findings suggest a possible microbial basis for antidepressant efficacy in PD patients, highlighting the potential of microbiota-targeted therapies to improve depression outcomes and guide future therapeutic strategies for neurodegenerative diseases.