Document resource
Background The microbiota-gut-brain axis represents an emerging therapeutic target for neuropsychiatric disorders, particularly depression. We evaluated the efficacy and safety of a novel psychobiotic formula (MQU10) in a clinical study and explored its underlying mechanisms through preclinical models.Methods In multi-centre pilot study, we recruited adults with moderate depressive symptoms based on the Patient Health Questionnaire-9 (PHQ-9). Subjects received MQU10 (20 billion CFU/day consisting of Bifidobacterium, Lactobacillus, and prebiotics) orally for 6 weeks. Primary outcome was the proportion of subjects who achieved clinical improvement on the Clinical Global Impression-Improvement (CGI-I) scale at week 6. Secondary outcomes included changes in PHQ-9, Generalised Anxiety Disorder-7 (GAD-7), World Health Organisation Quality of Life-Brief Version (WHOQOL-BREF), Patient Global Impression of Change (PGI-C), safety, and changes in faecal microbiome. The trial registered at ClinicalTrials.gov (NCT06905223) and Chinese Clinical Trial Registry (ChiCTR2600116796). Complementary mechanistic studies were conducted using an in vitro microglial-neuronal coculture model and an in vivo chronic unpredictable mild stress.Results Between 3 April and 12 June 2025, 43 participants were enrolled42 completed follow-up and were included in the per-protocol analysis, with 41 assessed for CGI-I outcomes. At week 6, 82.9% (34/41; 95% CI: 67.9%-92.8%) achieved clinical improvement (CGI-I ≤3), and 57.1% achieved marked improvement (CGI-I ≤2). Mean PHQ-9 decreased from 12.1±1.2 to 7.5±4.0 (p<0.001), and mean GAD-7 decreased from 9.3±3.5 to 6.2±4.1 (p<0.001). Significant improvements were observed across all WHOQOL-BREF domains (p<0.05). No serious adverse events were reported. Faecal microbiome analysis showed compositional shifts with significant increases in supplemented bacteria strains at week 6. Clinical improvement correlated with increased beneficial taxa, including Akkermansia muciniphila and downregulation of propionate and Lalanine degradation pathways (p < 0.05).In preclinical studies, MQU10 reduced pro-inflammatory cytokines expression in vitro and alleviated depression-like behaviours in CUMS mice model (p<0.05).Conclusions This integrated preclinical and clinical investigation demonstrates that the multistrain psychobiotic formulation MQU10 alleviates depressive symptoms through modulation of the gut-brain axis, with domainspecific symptom improvements and a favourable safety profile.This study was supported by InnoHK, The Government of Hong Kong, China.