ABSTRACTABSTRACTObjective The main purpose of the present study was to assess the beneficial effect of Lactobacillus plantarum GM11 (LacP GM11), screened from Sichuan traditional fermented food, in depressive rats induced by chronic unpredictable mild stress (CUMS).Methods Male SPF SD rats were randomly assigned to 3 groups: the control group, CUMS group and CUMS + LacP GM11 group (n = 10). The rats in the CUMS and LacP GM11 groups received CUMS stimulation for 42 d. The behavioral tests and levels of monoamine neurotransmitter, glucocorticoid hormone and brain-derived neurotrophic factor (BDNF) in the serum and hippocampus were measured. The effects of LacP GM11 on the mRNA and protein expression of BDNF and cAMP response element binding protein (CREB) in the hippocampus were also investigated.Results After supplementation for 21 d, LacP GM11 was associated with alleviation of depressive-like behavior, not anxiety-like behavior, in depressive rats. LacP GM11 increased the levels of 5-hydroxytryptamine (5-HT) and BDNF and decreased the level of cortisol (CORT) in the serum and hippocampus in depressed rats. In addition, treatment with LacP GM11 also increased the mRNA and protein expression of BDNF and CREB in the hippocampus.Conclusions This work has revealed that LacP GM11 has potential beneficial effects on depression. This effect might be related to alleviating monoamine neurotransmitter deficiency, HPA axis hyperfunction and CREB-BDNF signaling pathway downregulation. This study demonstrates that LacP GM11 could be a potential therapeutic approach to treat depression and other mental health problems.KEYWORDS: Lactobacillus plantarumchronic unpredictable mild stressdepressionprobioticspsychobioticsHypothalamic-Pituitary-Adrenal (HPA) axisbrain-derived neurotrophic factor (BDNF)cAMP response element binding protein (CREB) Disclosure statementNo potential conflict of interest was reported by the author(s).Data availability statementThe authors declare that all data associated with the current study are available from the corresponding authors upon reasonable request. The data are not publicly available due to restrictions in the process of patent application.Additional informationFundingThis work was supported by the Sichuan Science and Technology Program from the Science & Technology Department of Sichuan Province of People' s Republic of China (Program Nos. 2022YFQ0006 and 2022ZYD0096).Notes on contributorsJie MaJie Ma, PhD in Biological Engineering, works in the Department of Research and Development at Weichuang Tianyi Biotechnology Co., Ltd.Junrui WangJunrui Wang is a PhD candidate in Savaid Medical School at University of Chinese Academy of Sciences and works in the Department of Orthopaedics, Chengdu Second People's Hospital.Gang WangGang Wang is a Senior Engineer in the Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd.Yujun WanYujun Wan is a Senior Engineer in the Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd.Nanzhen LiNanzhen Li is an Engineer in the Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd.Lijuan LuoLijuan Luo is an Engineer in the Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd.Hongmei GouHongmei Gou is an Assistant Engineer in the Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd.Jianwen GuJianwen Gu, PhD in Biological Engineering, is a professor in the Department of Neurosurgery at PLA Strategic Support Force Characteristic Medical Center.