Major depressive disorder (MDD) is a complex mental disorder, potentially linked to the gut-microbiota-brain axis. Probiotics like Lactobacillus plantarum PS128 (PS128) may improve depressive symptoms by modulating the gut microbiota based on our previous open trial. We conducted an 8-week double-blind, placebo-controlled trial to investigate the impact of PS128 on depression severity, markers of inflammation and gut permeability, and the gut microbiota composition in 32 patients with MDD with stable antidepressant treatment but moderate symptom severity. Following the 8-week intervention, both the Hamilton Depression Rating Scale-17 score (HAMD), and Depression and Somatic Symptoms Scale (DSSS) showed a significant decrease in both groups (p<0.001). However, there was no significant difference in the change of depression severity between groups (p=0.203). Moreover, alterations in serum levels of high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and intestinal fatty acid binding protein, as well as changes in the gut microbiota composition, did not exhibit significant differences before and after intervention or between the groups. In comparison to the placebo group, our study did not find significant effects of PS128 on depressive symptoms, biomarkers of inflammation and gut permeability, and the overall gut microbiota composition. Nonetheless, we observed a potential impact of PS128 on the symbiosis of specific taxa. To comprehensively understand the psychophysiological effects of PS128 in patients with MDD, further research with a larger sample size is imperative.
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