Peijun Tian1, Ying Chen1, Huiyue Zhu1, Luyao Wang1, Xin Qian1, Renying Zou1, Jianxin Zhao2, Hao Zhang3, Long Qian4, Qun Wang4, Gang Wang5, Wei Chen6. 1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. 2. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu 225004, China. 3. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu 225004, China; Wuxi Translational Medicine Research Center, Jiangsu Translational Medicine Research Institute, Wuxi, Jiangsu 214122, China. 4. The Tinghu People's Hospital, Yancheng, Jiangsu 224002, China. 5. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu 225004, China. Electronic address: wanggang@jiangnan.edu.cn. 6. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China.
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.
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.
Authors: Sauliha R Alli; Ilona Gorbovskaya; Jonathan C W Liu; Nathan J Kolla; Lisa Brown; Daniel J Müller Journal: Int J Mol Sci Date: 2022-04-19 Impact factor: 6.208