The Gut Microbiota Is Altered in Antidepressant-Free Depressed Patients and Is Associated With Depression Severity

Interest in the microbiota-gut-brain axis is increasing, but data on the associations between the microbiota and major depressive disorder (MDD), particularly in relation to symptomatology and treatment response, remain scarce and inconsistent. This study aims at characterizing the gut microbiota of antidepressant-free MDD patients with a Major Depressive Episode (MDE) in comparison to healthy controls (HCs) and to investigate whether microbiota composition is associated with depression severity. Twenty-five adults with a current MDE, who had been antidepressant-free for at least 1 month, were evaluated for both depression severity and fecal microbiota composition using 16S rRNA sequencing. Their microbiota profiles were compared with those of twenty-eight HCs. Psychiatric assessments were conducted at baseline using the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression (CGI) scale. Compared to HCs, MDE patients showed no significant differences in microbial alpha diversity. However, alterations in the relative abundance of several taxa, including Lachnospiraceae and Bifidobacteriaceae, along with an increase in Bifidobacterium, were detected. Beta-diversity analyses (PCoA plot) identified two distinct compositional clusters. Significant alterations were found in 7 out of 25 families and 20 out of 61 genera, with a notable decrease of the Lachnospiraceae NK4A136 genus in MDE patients, which was associated with worse symptom severity. These findings reveal distinct alterations in the gut microbiota of antidepressant-free MDE patients compared to HCs, particularly in key phyla and families. They suggest that the gut microbiota may represent a novel target for the management and treatment of MDD.