Gut microbiota - a new mechanism of action involved in the antidepressant effects of Hypericum perforatum?

St. John´s wort (Hypericum perforatum L.) is widely used for mild to moderate depressive disorders. Despite numerous clinical studies and meta-analyses, the mechanism of action and the responsible constituents are not fully elucidated. With the overall aim to investigate the role of gut microbiota for the activity of herbal preparations in mental health, a hydroethanolic extract of H. perforatum (STW 3-VI) was subjected to in-vitro upper gastrointestinal tract digestion (1), and subsequently incubated ex-vivo with fecal samples from ten healthy donors (24h, anoxic, 37°C) (2). DNA extraction, followed by 16S rRNA gene sequencing, was used to evaluate the shift in microbial community composition during the incubation. Differential abundance analysis was performed using the combination of CLR abundances as input and Wilcoxon for dependent samples/Mann-Whitney U test for independent samples. The analysis showed that 2 phyla, 7 families, 9 genera and 21 OTUs were significantly modulated by treatment with H. perforatum. Many of the significantly changing taxa have been associated with depression. For example, H. perforatum treatment enhanced the Firmicutes/Bacteroidetes ratio, and decreased the levels of Odoribacter (p= 0.0007) and Erysipelotrichaceae_UCG-003 (p= 0.034) (opposite effects have been observed for individuals with depression (3)). Provided that they also occur in-vivo, these changes in the microbial community composition suggest a potential additional non-CNS mediated mechanism of action for the antidepressant effects of H. perforatum.