Bifidobacterium breve CCFM1025 Attenuates Major Depression Disorder via Regulating Gut Microbiome and Tryptophan Metabolism: A Randomized Clinical Trial – ScienceDirect

Bifidobacterium breve CCFM1025 Attenuates Major Depression Disorder via Regulating Gut Microbiome and Tryptophan Metabolism: A Randomized Clinical Trial

Highlights

CCFM1025 attenuates psychiatric and gastrointestinal abnormalities of MDD patients.


CCFM1025 can regulate the host’s serotonergic system.


CCFM1025 caused slight perturbation on the patients’ gut microbial composition.


CCFM1025 significantly changed the gut microbiome’s tryptophan metabolism.

Abstract
Objective
Psychobiotics, as a novel class of probiotics mainly acting on the gut-brain axis, have shown promising prospects in treating psychiatric disorders. Bifidobacterium breve CCFM1025 was validated to have an antidepressant-like effect in mice. This study aims to assess its psychotropic potential in managing major depression disorder (MDD) and unravel the underlying mechanisms.

Methods
Clinical Trial Registration: https://www.chictr.org.cn/index.aspx (identifier: NO. ChiCTR2100046321). Patients (n=45) diagnosed with MDD were randomly assigned to the Placebo (n=25) and CCFM1025 (n=20) groups. The freeze-dried CCFM1025 in a dose of viable bacteria of 1010 CFU was given to MDD patients daily for four weeks, while the placebo group was given maltodextrin. Changes from baseline in psychometric and gastrointestinal symptoms were evaluated using Hamilton Depression Rating scale-24 Items (HDRS-24), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Gastrointestinal Symptom Rating Scale (GSRS). Serum measures were also determined, i.e., cortisol, TNF-α, and IL-β. Serotonin turnover in the circulation, gut microbiome composition, and tryptophan metabolites were further investigated for clarifying the probiotics’ mechanisms of action.

Results
CCFM1025 showed a better antidepressant-like effect than placebo, based on the HDRS-24 (placebo: M=6.44, SD=5.44; CCFM1025: M=10.40, SD=6.85; t(43)=2.163, P=0.036, d=0.640) and MADRS (placebo: M=4.92, SD=7.15; CCFM1025: M=9.60, SD=7.37; t(43)=2.152, P=0.037, d=0.645) evaluation. The factor analysis of BPRS and GSRS suggested that patients’ emotional and gastrointestinal problems may be affected by the serotonergic system. Specifically, CCFM1025 could significantly and to a larger extend reduce the serum serotonin turnover compared with the placebo (placebo: M=-0.01, SD=0.41; CCFM1025: M=0.27, SD=0.40; t(43)=2.267, P=0.029, d=0.681). It may be due to changes in gut microbiome and gut tryptophan metabolism under the probiotic treatment, such as changes in alpha diversity, tryptophan, and indoles derivatives.

Conclusion
B. breve CCFM1025 is a promising candidate psychobiotic strain that attenuates depression and associated gastrointestinal disorders. The mechanisms may be relevant to the changes in the gut microbiome and tryptophan metabolism. These findings support the future clinical applications of psychobiotics in the treatment of psychiatric disorders.

Graphical abstract
A previously isolated psychobiotic strain, Bifidobacterium breve CCFM1025, is tested for psychotropic potential in major depression disorder patients. A four-week CCFM1025 intervention significantly attenuates the psychiatric and gastrointestinal abnormalities, and the mechanisms may involve the regulations on the serotonergic system and gut microbiome’s tryptophan metabolism.

— Read on www.sciencedirect.com/science/article/abs/pii/S0889159121006267

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