The Impact of Weizmannia coagulans BC99 on Anxiety and Depression: An 8-Week Clinical Pilot Study Through the Gut Microbiota–Brain Axis

<b>Background</b>: An imbalance in the immune system, stress response, and gut microbiota can contribute to the onset and progression of anxiety and depression. This pilot study aimed to explore the effect of <i>Weizmannia coagulans</i> BC99 on anxiety and depression through the gut microbiota-brain axis. <b>Methods</b>: A total of 79 participants with Hamilton Depression Rating Scale (HAMD-17) ≥ 8 or Hamilton Anxiety Rating Scale (HAMA-14) ≥ 7 were included and completed the study. The participants were randomly assigned to either the placebo group or the BC99 intervention group. The intervention lasted 8 weeks, with participants receiving either dextrin (3 g/day) or BC99 probiotics (3 g/day, 5 × 10⁹ CFU) daily. Pre- and post-intervention comparisons were made on HAMD and HAMA scores, inflammatory cytokines, neurotransmitters, gut microbiota, and short-chain fatty acids. <b>Results</b>: Results showed that after 8 weeks, BC99 and placebo intervention were effective in reducing HAMD and HAMA scores, and HAMD and HAMA scores in BC99 group were reduced by 2.40 and 5.53 points compared the placebo group, and the response and remission rates were also higher than that of the placebo, but there was no significant difference. BC99 also could regulate the levels of inflammatory cytokines IL-17 and IL-10, and increase neurotransmitter levels of γ-GABA and NO. Moreover, compared with the placebo group, BC99 also enhanced the abundance of beneficial bacteria such as <i>Faecalibactrium</i>, <i>Megamonas</i>, <i>Dialister</i>, and <i>Agathobacter</i>, which were closely associated with clinical indicators of mental disorders, and increased the production of short-chain fatty acids. <b>Conclusions</b>: These preliminary findings suggested that BC99 might alleviate anxiety and depression symptoms by regulating the level of neurotransmitters or the change of microbiota, which needed further verification in subsequent animal or clinical experiments.