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Page 2 of 14 Tian et al. Microbiome Res Rep 2024;3:49 https://dx.doi.org/10.20517/mrr.2024.33

Metabolomic profiling identified elevated levels of fecal lactic acid, which correlated with lower Hospital Anxiety
and Depression Scale (HADS) scores, thereby linking probiotic metabolism to mood enhancement.

Conclusion: These findings imply that CCFM6432 may improve brain function by modulating gut microbiota and
their mediated immune homeostasis, underscoring its potential as an adjunctive treatment for mental disorders.

Keywords: Pediococcus acidilactici, depression, gut microbiota, lactic acid, immune

INTRODUCTION
Depression, as a psychiatric disorder with complex etiology, has garnered widespread attention globally.
According to projections by the World Health Organization, depression is expected to become the leading
cause of global disease burden by 2030 . Particularly in the post-pandemic era, there has been a significant
[1]
[2]
increase in the risk of mood disorders worldwide . However, due to the intricate pathogenesis of
depression and substantial individual variations, the selection and efficacy of antidepressant medications are
[3,4]
currently greatly constrained . Drugs widely used in clinical practice, such as selective serotonin reuptake
inhibitors and serotonin-norepinephrine reuptake inhibitors, often yield remission rates of less than 50% .
[5]
In recent years, with the continuous expansion of knowledge related to the “gut-brain axis”, the correlation
and even causality between changes in gut microbiota and mental health status have been gradually
[6]
established . The gut microbiota can participate in or promote the synthesis of various neurotransmitters,
such as acetylcholine, γ-aminobutyric acid, and glutamate, thereby influencing the host’s emotions,
memory, and cognitive function . Compared to healthy individuals, patients with depression exhibit
[7]
significant differences in gut microbial composition and often experience various gastrointestinal
dysfunctions [8-10] . Transplanting fecal microbiota from patients with depression into the intestines of healthy
[11]
mice can induce depressive-like behavior in the mice . Conversely, transplanting gut microbiota from
healthy volunteers into the intestines of patients with anxiety or depression has been shown to significantly
reduce the patients’ anxiety and depression scores [12,13] . However, fecal microbiota transplantation faces
significant potential safety risks, and the lack of donor screening and recipient adaptability assessment
methods limits its widespread use in the treatment of depression .
[14]
Nevertheless, this has not deterred researchers from exploring alternative approaches to harnessing the gut
microbiota to improve emotional well-being. A plethora of preclinical studies suggest that the ingestion of
probiotics can inhibit the occurrence of organismal inflammation and cortisol levels, reduce stress
responses, enhance memory, and decrease the occurrence of host mood disorder-related symptoms [10,15,16] .
These beneficial live organisms to host mental health are defined as “Psychobiotics” . However, the
[17]
positive effects of psychobiotics on depressive symptoms have shown inconsistent results in clinical trials. A
systematic review based on 13 clinical trials revealed that while the results of seven trials (including reports
from three independent cohorts of the same strain) confirmed a significant reduction in depression scores
during probiotic supplementation, the remaining six trials did not yield beneficial outcomes . This
[18]
inconsistency is believed to be due to significant variations among different strains. Therefore, elucidating
the material basis and mechanisms by which specific effective strains alleviate depression will greatly
promote the selection and application of psychobiotics.

In this context, our previous research has demonstrated that continuous intake of a composite probiotic
formulation containing Pediococcus acidilactici CCFM6432 can improve symptoms in patients with severe
[19]
depression . Furthermore, we confirmed through a chronic stress animal model that intervention with the
single strain CCFM6432 can alleviate anxiety-like behaviors in mice. The aim of this study is to