Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1

Abstract

Recent investigations have demonstrated that the chronic stress-induced behavioral disorders can be ameliorated by probiotics including Clostridium butyricum (C. butyricum) via the gut-brain-axis. However, the molecular mechanisms underlying the beneficial effects of C. butyricum on brain remain largely unknown. Here, we investigated whether chronic foot shock stress (CFSS) paradigm used for a hypertensive animal model could induce mood disorders such as anxiety, depression and cognitive impairments. Then, we assessed the impact of C. butyricum RH2 on the behavior disorders and neurobiological alterations in the hippocampus. Male Sprague-Dawley (SD) rats received intermittent electric shocks for consecutive 14 days and were treated with C. butyricum RH2 for 17 days. Anxiety- or depression-like behaviors were evaluated by open field test (OFT), and elevated plus maze (EPM). The Morris water maze test (MWM) was used to evaluate the cognitive functions. CFSS intervention led to mild anxiety- or depression-like behavior or cognitive impairment and C. butyricum RH2 treatment reversed the CFSS-induced symptoms. The serum ACTH or CORT was increased following CFSS but was completely reversed by C. butyricum RH2 treatment. In the hippocampus of CFSS rats, the expressions of BDNF and TrkB were downregulated but proBDNF and P75NTR were upregulated. These expression changes were partially reversed by C. butyricum RH2, suggesting a mode of action on BDNF and proBDNF balance. CFSS exposure resulted in downregulation of tissue-type plasminogen activator (tPA) but upregulation of plasminogen activator inhibitor 1(PAI-1), which could contribute to the decrease in BDNF by reduced conversion from proBDNF to BDNF in the hippocampus. C. butyricum RH2 treatment reversed the upregulated PAI-1 but not the downregulated tPA, which was in parallel with the amelioration of behavioral abnormalities, suggesting a novel tPA independent mechanism for PAI-1 action. Our results demonstrate for the first time that C. butyricum RH2 attenuates stress-induced behavior disorders via inhibiting the expression of brain PAI-1.

Probiotics for the treatment of depression and its comorbidities: A systemic review

“…Fibrinolytic enzymes are converted from fibrinogen in the presence of tissue plasminogen activator, which can be inhibited by plasminogen activator inhibitor-1 (PAI-1), leading to the accumulation of pro-BDNF. Previous studies found that PAI-1 increases in the prefrontal cortex and hippocampus of chronically stressed rats (Party et al, 2019;Zhang W. et al, 2022). The decreased BDNF can be found in patients with depression (Jiang et al, 2015;Youssef et al, 2018), whereas antidepressant treatment can increase the levels of BDNF (Martinotti et al, 2016).…”

“…In fact, recent findings suggest that probiotics may improve host health in patients with IBS both physically and mentally (Le Morvan De Sequeira et al, 2021;Zhang T. et al, 2022). The safety and efficacy of probiotics in the treatment of IBS are supported by numerous clinical studies.…”

“…The safety and efficacy of probiotics in the treatment of IBS are supported by numerous clinical studies. A systematic review and network meta-analysis of 43 RCTs involving 5,531 IBS patients provided data regarding the best probiotic species used in the treatment of IBS (Zhang T. et al, 2022). Several probiotic strains, such as B. bifidum, B. infantis, L. casei, L. acidophilus, L. plantarum, Bacillus coagulans, C. butyricum, and Saccharomyces boulardii alone or in combination, have been used to treat depression in patients with IBS.…”