A Promising Adjunctive Therapy: Pediococcus acidilactici CCFM6432 as a Targeted Psychobiotic for Anhedonia in Major Depressive Disorder

Gabriel McLaughlin

Study Objective

The objective of this study was to evaluate the efficacy of Pediococcus acidilactici CCFM6432 as an adjunctive treatment to antidepressant therapy in alleviating anhedonia in patients with Major Depressive Disorder (MDD). The trial used a combination of clinical subjective assessments, objective neurophysiological measures, and feedback-related negativity amplitudes via electroencephalography over a 30-day intervention period.

Key Takeaway

Adjunctive Pediococcus acidilactici CCFM6432 significantly improves anticipatory anhedonia in major depressive disorder, offering a safe, cost-effective, and targeted therapy for treatment of resistant symptoms with potential relevance for co-occurring gastrointestinal issues of MDD.

Design

A randomized, double-blinded, placebo-controlled trial conducted from March 2023 to June 2024 at Wuxi Mental Health Center, including 71 adults between the ages of 18 and 65 with Major Depressive Disorder (MDD) and accompanying symptoms of anhedonia described by a score of 3 or greater on the Snaith-Hamilton Pleasure Scale (SHAPS). All included patients were on a stable antidepressant treatment plan previously outlined by their psychiatrist. Participants were randomized into two groups. The treatment group received standard antidepressant therapy alongside Pediococcus acidilactici CCFM6432, and the placebo group received standard antidepressant therapy alongside a placebo. The trial lasted 30 days, and clinical outcomes were assessed using the Hamilton Depression Rating Scale (HAMD), Temporal Experience of Pleasure Scale (TEPS), and electroencephalography (EEG) during a Doors Guessing Task measuring stimulus-preceding negativity (SPN) and feedback-related negativity (FRN) amplitudes.

Participants

Of 92 screened patients, 71 adults (aged 18 to 65, primary school education or higher) with MDD and anhedonia (SHAPS score >/= 3) were enrolled. Exclusion criteria included comorbid psychiatric conditions such as bipolar disorder, schizophrenia, etc., severe illness such as cardiovascular disease, antibiotic or probiotic use within the last 30 days, or modified electroconvulsive therapy. 55 participants completed the study (Intervention n=27, 10 males/ 17 females, placebo n=28, 11 males/ 17 females). Six participants in the intervention group and four participants in the control group were dropped during the study due to changes in antidepressant medications. Additionally, three participants in each group were excluded mid-study due to non-compliance.

Intervention

Both groups received their normal antidepressant dose as previously outlined by their psychiatrist. The treatment group also received Pediococcus acidilactici CCFM6432 at a dose of > 109 CFU/ sachet / day for 30 days. The placebo group also received a biologically inactive placebo sachet that was identical in appearance and taste to the Pediococcus acidilactici CCFM6432 sachet. Participants were instructed to maintain their normal diet and exercise routines and were encouraged to avoid alcohol. Additionally, participants were instructed to report any antibiotic use. Adherence was monitored via empty sachets, and by nurses for inpatient participants and family members for outpatient participants.

Study Parameters Assessed

The study collected both subjective and objective data. Primary outcomes centered on anhedonia and were assessed by the Temporal Experience of Pleasure Scale (TEPS) total score, along with its anticipatory (ANT) and consummatory (CON) subscales. Anticipatory anhedonia reflects difficulty in anticipating pleasure, such as excitement about future events. Consummatory anhedonia involves reduced enjoyment during pleasurable activities. Objective measure of reward processing included EEG-based stimulus-preceding negative (SPN) and feedback-related negativity (FRN) amplitudes during a Doors Guessing Task. Secondary outcomes included depression severity using the Hamilton Rating Depression Scale (HAMD), and anxiety severity using the Hamilton Anxiety Rating Scale (HAMA). Baseline assessments were obtained, and post-intervention assessments were obtained within three days of completion of the 30-day trial. 

Primary Outcome the study was designed to assess

The primary outcomes assessed were changes in anhedonia severity, measured by the Temporal Experience of Pleasure Scale (TEPS) total score and its anticipatory (ANT) and consummatory (CON) subscales for subjective anhedonia, and EEG-based stimulus-preceding negative (SPN) and feedback-related negativity (FRN) amplitudes for objective reward processing.

Key Findings

The study provides compelling evidence in favor of Pediococcus acidilactici CCFM6432 as an adjunctive treatment for MDD with anhedonia. The CCFM6432 group (n=27) demonstrated significantly greater improvements compared to the placebo group (n=28) in depression severity as measured by the HAMD scale (p=0.013, np2=0.112), and significant improvements in anhedonia as measured by TEPS scores (p=0.041, np2=0.076), specifically for anticipatory anhedonia (TEPS ANT, P=0.015, np2=0.106). Electroencephalography (EEG) during the Doors Guessing Task revealed a significant increase in stimulus-preceding negativity (SPN) amplitude in the CCFM6432 group (P=0.031, ηp²=0.085), indicating enhanced neural reward anticipation. The intervention group also had improved HAMA scores (P=0.011, np2=0.117). There were, however, no notable changes in FRN amplitudes (P=0.686, np²=0.003) or consummatory anhedonia (P=0.293, np²=0.021) between groups. Major limitations include a modest, single-center sample, lack of dietary standardization, and lack of biomarker analysis, as certain cytokines such as TNF-alpha, IL-6, and CRP could help clarify the mechanisms of action related to results.7 Additionally, the one-month washout period for prior antibiotic/probiotic use may be insufficient to normalize gut microbiota, potentially influencing outcomes. The lack of baseline gut health standardization, such as a fecal microbiota analysis, further complicates interpretation, as varying degrees of dysbiosis could affect probiotic efficacy.

Transparency

There is no acknowledgement of referencing any grants, institutional funding, or external contributions. The probiotic used in the study was developed by the School of Food Science and Technology at Jiangnan University and several authors are affiliated with that institution. It was explicitly stated, however, that the authors have no conflicts of interest to declare.

Practice Implications & Limitations

This study underscores the therapeutic potential of Pediococcus acidilactici  CCFM6432 in managing MDD with anhedonia, a symptom often linked to gut dysbiosis and inflammation, common in conditions such as SIBO and IBS.1 Pediococcus acidilactici  CCFM6432 was selected for this trial based on prior preclinical evidence of its ability to modulate the gut-brain axis, reduce neuroinflammation, and improve depressive-like behavior in animal models. In a 2023 randomized trial of multi-probiotic formulations including CCFM6432, MDD patients experienced significant reductions in gastrointestinal symptoms, including gut motility dysfunction and abdominal discomfort, alongside decreased depression severity, mediated by serotonergic system regulation.2 Similarly, a 2024 single-strain trial demonstrated CCFM6432’s efficacy in alleviating overall depressive symptoms, sleep disturbances, and comorbid GI dysfunction in depressed patients with effects attributed to gut-microbiota shifts.3 These findings align with a broader and growing body of evidence supporting pyschobiotics in the management of depression. Multiple randomized controlled trials have demonstrated benefits from other genera and strains, including Lactobacillus and Bifidobacterium species often used in multi-strain formulations.4 Recent meta-analyses confirm modest but statistically significant antidepressant effects of probiotics, particularly when used as adjunctive therapy in clinical populations with major depressive disorder.5 For example, a 2025 systematic review and meta-analysis of randomized controlled trials in clinically diagnosed samples found that probiotics produced substantial reductions in depression symptoms and moderate reductions in anxiety symptoms.6 Another 2023 meta-analysis concluded that probiotic containing interventions significantly improved depression symptoms compared with placebo.7 Pediococcus acidilactici CCFM6432 showed selective improvement in anticipatory anhedonia (TEPS-ANT), but not consummatory pleasure (TEPS-CON), suggesting it preferentially targets reward anticipation pathways rather than hedonic consumption. This distinction is clinically meaningful, as anticipatory deficits are more strongly tied to inflammatory signaling and gut-brain axis dysfunction than consummatory deficits.9,10 Anhedonia in MDD often arises from gut-dysbiosis and chronic low-grade inflammation that disrupts the gut-brain axis via increased intestinal permeability, bacterial lipopolysaccharide (LPS) translocation, elevated pro-inflammatory cytokines such as TNF-alpha and IL-6, impaired vagal signaling, and microglial activation in the hippocampus.6,7,8 Mechanistically, P. acidilactici CCFM6432 may exert its effects through anti-inflammatory modulation of the gut-brain axis, potentially via LPS reduction, downregulation of hippocampal microglial activation, or enhanced vagal signaling pathways previously implicated in reward processing and mood regulation.3 The observed negative correlation between SPN amplitude increases and HAMD score improvements further supports a neural basis for these clinical benefits, reinforcing the probiotic’s role in restoring reward anticipation circuitry. The efficacy on anticipatory anhedonia is relevant, as it helps address root causes of anhedonia, rather than merely addressing symptom palliation. Pediococcus acidilactici CCFM6432 is also a valuable treatment option as it appears to be safe, cost-effective, and can easily be integrated into treatment plans for patients with MDD and comorbid GI symptoms. It complements anti-inflammatory dietary interventions (low-FODMAP, Mediterranean, etc.), and botanicals (Curcuma longa, Zingiber officinale) that similarly target gut permeability and neuroimmune activity. Given its specificity for anticipatory anhedonia, it is particularly suited for patients with treatment-resistant depressive symptoms or those seeking to minimize pharmaceutical use. Currently, Pediococcus acidilactici CCFM6432 is not widely commercially available as a single-strain product; there are a select number of products that contain Pediococcus acidilactici CCFM6432 in formulation. Additionally, other P. acidilactici strains are found in various multi-strain probiotic formulations. 

One limitation, to this study is the absence of pre- and post-intervention gastrointestinal symptoms assessment leaving clinicians with a lack of data on gut function impact. While prior evidence does suggest CCFM6432 may improve GI symptoms in patients with MDD, there is no direct data on the use of CCFM6432 in patients with pure MDD and no GI symptoms.  

Additionally, it may be beneficial for clinicians to monitor adherence when trialing Pediococcus acidilactici CCFM6432. Baseline gut-health assessments through stool testing should also be considered to help personalize therapy while offering deeper insight into how CCFM6432 may affect the gut microbiome. Dysbiosis markers that may predict response, such as reduced  Bifidobacterium levels, elevated Escherichia shigella, increased fecal LPS/ endotoxin, or leaky gut indicators like zonulin, could be considered. 

The findings of this study also help encourage integrative healthcare for mental health, where further advocacy for combining lifestyle, diet, and supplemental intervention with mindfulness and stress reduction is warranted, as these interventions may amplify gut-brain axis benefits. Future research should focus on long-term efficacy, dose-response trials, and synergistic protocols with dietary or botanical interventions. A critical next step is a three-arm RCT comparing CCFM6432 alone, antidepressants, and a placebo to clarify its standalone efficacy. Inclusion of inflammatory markers such as IL-6, CRP, and LPS with a fecal microbiota profiling will further elucidate mechanisms and enable precision in clinical practice. 

Author Conflict of Interest

Gabriel McLaughlin declares no conflict of interest, financial or otherwise, related to this work. No funding was received for the preparation of this commentary. Pediococcus acidilactici CCFM6432 is not manufactured, distributed, or sold by the author or any affiliated entity. The commentary is based solely on the published study and publicly available literature

Reference

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