The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study

Objectives: (1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression. Design: Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958). Setting: Los Angeles, CA, USA (2016-2018) Participants: Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female. Intervention: Levomilacipran (LVM) or placebo. Measurements: Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses. Results: Baseline microbiota showed no community level alpha-diversity or beta-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters. Conclusions: This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.