Assessment of the beneficial effects of Lactobacillus rhamnosus GM12 on depression in both in vitro and in vivo models

Introduction Depression is a prevalent mental disorder that profoundly affects patients’ quality of life and work efficiency. The exploration of effective and safe treatment options remains a research focus for alleviating depression. This study aimed to assess the potential of Lactobacillus rhamnosus GM12 (GM12), newly isolated from traditional fermented foods for the treatment of depression in both in vitro and in vivo models. Methods We initially investigated the effects of GM12 on corticosterone (CORT)-induced injury in PC12 cells. Subsequently, the male Sprague-Dawley rats ( n = 10 per group) were randomly assigned into the control group, CUMS group, and CUMS + GM12 group. The CUMS and CUMS + GM12 groups were exposed to CUMS for 42 consecutive days. From day 22 to day 42, the CUMS + GM12 group received daily gavage of 10 mL/kg GM12. Behavioral tests, the serum and hippocampal levels of 5-HT, brain-derived neurotrophic factor (BDNF), hypothalamic-pituitary-adrenal (HPA) axis hormone and pro-inflammatory cytokines were measured. The protein expression of BDNF and cAMP response element binding protein (CREB) in the hippocampus were also analyzed. Additionally, the diversity and composition of the gut microbiota were evaluated. Results GM12 improved the viability of PC12 cells, reduced LDH release and apoptosis, thereby exerting protective effects against CORT-induced cell damage. GM12 administration significantly ameliorated depressive-like behaviors, restored 5-HT levels, normalized HPA axis hormone imbalances, reduced inflammatory response and upregulated of BDNF level and the BDNF/CREB protein expression in rats. The beneficial effects of GM12 may be mediated via multiple mechanisms, including regulation of gut microbiota composition and homeostasis, inhibition of inflammation and the modulation of the microbiota-gut-brain axis. Conclusions This study can provide early evidence for the research of in-depth mechanism and development of this strain. Overall, GM12 shows promise as a potential treatment strategy or dietary supplement for depression, with significant potential for future application.