Pediococcus acidilactici CCFM6432 alleviates anhedonia in major depression through immune-inflammatory modulation: An extended trial analysis

BACKGROUND Anhedonia in major depressive disorder remains therapeutically challenging. Building on our prior randomized evidence of clinical benefit with Pediococcus acidilactici CCFM6432, we further investigated candidate peripheral immune and central reward correlates of treatment response. AIM To evaluate whether add-on CCFM6432 alleviates anhedonia through immune-inflammatory modulation and changes in reward-related electrophysiological measures. METHODS Adults with major depressive disorder and anhedonia received standard antidepressant therapy plus CCFM6432 or plus placebo for 30 days. Assessments comprised Hamilton Depression Scale; Temporal Experience of Pleasure Scale (total, anticipatory, consummatory); event-related potentials indexing reward anticipation and feedback - stimulus-preceding negativity and feedback-related negativity; and a 13-marker peripheral panel (immune-inflammatory, neurotrophic, neurotransmitter-related). Of 92 screened, 71 were randomized; 55 completed (CCFM6432 group: n = 27; Placebo group: n = 28). RESULTS CCFM6432 produced greater reductions in lipopolysaccharide, C-reactive protein, and interleukin-6 vs placebo (P < 0.05). Decreases in these markers were aligned with improvements in the Temporal Experience of Pleasure Scale (total and anticipatory subscales) and with increased stimulus-preceding negativity amplitude, although the latter association attenuated after adjustment for depressive and anxiety symptom changes. No between-group differences were observed for neurotrophic or neurotransmitter-related measures, and feedback-related negativity showed no treatment-related effects. CONCLUSION These findings provide preliminary clinical support that immune-inflammatory modulation may contribute to the anhedonia-relieving effects of CCFM6432, particularly in reward anticipation. Larger multicenter studies with multimodal endpoints are warranted to confirm these results and elucidate mechanistic pathways.