Gut microbiome in atypical depression

Background: Recent studies showed that immunometabolic dysregulation is related to unipolar major depressive disorder (MDD) and that it more consistently maps to MDD patients endorsing an atypical symptom profile, characterized by energy-related symptoms including increased appetite, weight gain, and hypersomnia. Despite the documented influence of the microbiome on immune regulation and energy homeostasis, studies have not yet investigated microbiome differences among clinical groups in individuals with MDD. Methods: Fifteen MDD patients with atypical features according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-5, forty-four MDD patients not fulfilling the DSM-5 criteria for the atypical subtype, and nineteen healthy controls were included in the study. Participants completed detailed clinical assessment and stool samples were collected. Samples were sequenced for the prokaryotic 16S rRNA gene, in the V3-V4 variable regions. Only samples with no antibiotic exposure in the previous 12 months and a minimum of >2000 qualityfiltered reads were included in the analyses. Results: There were no statistically significant differences in alpha- and beta-diversity between the MDD groups and healthy controls. However, within the atypical MDD group, there was an increase in the Verrucomicrobiota phylum, with Akkermansia as the predominant bacterial genus. Limitations: Cross-sectional data, modest sample size, and significantly increased body mass index in the atypical MDD group. Conclusions: There were no overall differences among the investigated groups. However, differences were found at several taxonomic levels. Studies in larger longitudinal samples with relevant confounders are needed to advance the understanding of the microbial influences on the clinical heterogeneity of depression.