Li DX, Gu Y, Xia WJ, Sun YF, Hou L, Zhu WX, Wang J. Pediococcus acidilactici CCFM6432 alleviates anhedonia in major depression through immune-inflammatory modulation: An extended trial analysis. World J Psychiatry 2026; 16(3): 114446 [DOI: 10.5498/wjp.v16.i3.114446]
Corresponding Author of This Article
Jun Wang, MD, PhD, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, No. 156 Qianrong Road, Binhu District, Wuxi 214151, Jiangsu Province, China. woodfish2@126.com
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Psychiatry
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Randomized Controlled Trial
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Mar 19, 2026 (publication date) through Feb 28, 2026
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World Journal of Psychiatry
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2220-3206
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Li DX, Gu Y, Xia WJ, Sun YF, Hou L, Zhu WX, Wang J. Pediococcus acidilactici CCFM6432 alleviates anhedonia in major depression through immune-inflammatory modulation: An extended trial analysis. World J Psychiatry 2026; 16(3): 114446 [DOI: 10.5498/wjp.v16.i3.114446]
World J Psychiatry. Mar 19, 2026; 16(3): 114446 Published online Mar 19, 2026. doi: 10.5498/wjp.v16.i3.114446
Pediococcus acidilactici CCFM6432 alleviates anhedonia in major depression through immune-inflammatory modulation: An extended trial analysis
Jun Wang, Wen-Xian Zhu, Lu Hou, Yi-Fan Sun, Wen-Juan Xia, Yi Gu, Du-Xing Li
Du-Xing Li, Yi Gu, Wen-Juan Xia, Yi-Fan Sun, Wen-Xian Zhu, Jun Wang, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
Lu Hou, Department of Psychiatry, Huai’an Third People’s Hospital, Huai’an 223001, Jiangsu Province, China
Author contributions: Li DX, Xia WJ, and Wang J contributed to conceptualization; Li DX and Gu Y contributed to formal analysis; Gu Y, Sun YF, and Hou L contributed to software; Xia WJ, Hou L, and Zhu WX contributed to investigation; Xia WJ and Wang J contributed to writing - review and editing; Sun YF, Zhu WX, and Wang J contributed to resources; Li DX contributed to methodology, visualization, writing - original draft; Gu Y contributed to data curation; Zhu WX contributed to supervision; Wang J contributed to funding acquisition.
Supported by the Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee, No. BJ2023086; and Wuxi Taihu Talent Project, No. WXTTP 2021.
Institutional review board statement: This study received approval from the Ethics Committee of Wuxi Mental Health Center (No. WXMHCIRB2023 LLky030) and adhered rigorously to the principles of the Declaration of Helsinki.
Clinical trial registration statement: This study was retrospectively registered at https://www.chictr.org.cn/ (registration number: No. ChiCTR2400093687; date of registration: December 10, 2024).
Informed consent statement: Informed consent was obtained from all subjects involved in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Jun Wang, MD, PhD, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, No. 156 Qianrong Road, Binhu District, Wuxi 214151, Jiangsu Province, China. woodfish2@126.com
Received: September 19, 2025 Revised: November 6, 2025 Accepted: December 9, 2025 Published online: March 19, 2026 Processing time: 162 Days and 16.8 Hours
Abstract
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.
Core Tip: This study investigated whether Pediococcus acidilactici CCFM6432 alleviates anhedonia in major depressive disorder through immune-inflammatory modulation and reward-related electrophysiological changes. The probiotic significantly reduced inflammatory markers (lipopolysaccharide, C-reactive protein, and interleukin-6) and enhanced reward anticipation, as reflected by increased stimulus-preceding negativity amplitude and higher Temporal Experience of Pleasure Scale scores. These results suggest that CCFM6432 may improve anhedonia via an immune-inflammatory pathway. Large-scale, multicenter studies integrating multimodal biomarkers are warranted to validate and extend these findings.
