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

Abstract

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 α-diversity or β-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.

Gut Microbiome Diversity and Abundance Correlate with Gray Matter Volume (GMV) in Older Adults with Depression

“…Participants were recruited from geriatric ambulatory care settings (UCLA Geriatric Medicine-Psychiatry clinics) and from local advertisements to participate in the parent clinical trial of levomilnacipran for geriatric depression (NCT 02466958) that was previously reported elsewhere [ 27 , 49 ]. Of 29 randomized patients, 16 older adults (37.5% female; mean age, 70.6 (SD = 5.7) years; Table 1 ) completed both MRI and stool sample collection and were included in this report.…”

“…In addition to the existing neuroimaging data, an emerging and promising area of biological GD mechanisms is that of gut microbiota [ 27 ]. The gut microbiota, as the largest reservoir of microbes in the human body, have an essential role in the central nervous system (CNS) functioning through the bidirectional gut–brain axis [ 28 , 29 , 30 ].…”

“…Gut microbiota composition and diversity change across the lifespan and are likely responsible for higher susceptibility to immune weaknesses and diseases at older ages [ 48 ]. We previously demonstrated that antidepressant treatment response in GD was predicted by an enrichment in Faecalibacterium, Agathobacter, and Roseburia: individual taxa which significantly distinguished remitters from non-remitters [ 27 ]. In addition, we previously found treatment-related changes in differential abundance in remitters.…”

Utilization of Host and Microbiome Features in Determination of Biological Aging

“…Beyond diagnostic and prediction of diseases, the gut microbiome data could also be useful in the prediction of responsiveness to treatment in multiple age-related diseases. For instance, a recent prospective pilot study has shown that the microbial taxonomic composition of elderly with geriatric depression may be indicative of their response to antidepressants [ 134 ]. In another study, the baseline composition of the fecal microbiome, particularly the relative abundance of Faecalibacterium prausnitzii , was used to predict whether Crohn’s disease patients would experience a clinical relapse following discontinuation of immunosuppressive therapy [ 135 ].…”

Gut Microbiota Composition and Functional Prediction in Recurrent Spontaneous Abortion

“…Jin M et al found that Prevotella.9 were signi cantly decreased in patients with positive immune antibodyassociated recurrent abortion [28]. The enrichment of Faecalibacterium, Agathobacter and Roseburia were related to geriatric depression [35].…”