Lactobacillus delbrueckii alleviates depression-like behavior through inhibiting toll-like receptor 4 (TLR4) signaling in mice

Abstract

Background: The intestinal flora can influence behavior through the microbiota-gut-brain axis and is closely related to the occurrence and development of nervous system diseases such as depression. Probiotics like Lactobacillus may regulate the balance of the intestinal flora and play an active role in preventing and treating depression.Methods: Eight-week-old C57BL/6J mice (n=32) were randomly and equally divided into a normal control group, a control + Lac group, a model group, and a model + Lac group. The model and model + Lac groups were intraperitoneally injected with 1.2 mg/kg lipopolysaccharide for 7 days, and the behavior of the mice was assessed 24 hours later. The normal and model groups received intragastric administration of saline daily, while the control + Lac and model + Lac groups were given 10 9 cfu Lac intragastrically daily for 7 days. The inhibitory effect of Lac and its fermentation products on depression-related bacteria were examined in vitro.Results: Lac effectively inhibited the production of depression-like behaviors in mice. The expression levels of zonula occludens-1 (ZO-1) and E-cadherin in the small intestine in the model group were significantly decreased, but Lac abrogated this effect. Overactivation of microglia and decreased expression of dopamine transporter (DAT) in brain tissues, which are closely related to depression, were also abrogated by Lac treatment. Furthermore, the expression of toll-like receptor 4 (TLR4) and nod-like receptor protein-3 (NLRP3), as well as the level of interleukin-1 beta (IL-1β) in the intestine and brain, were all significantly increased; however, these effects were subsequently abrogated by Lac. Moreover, Lac inhibited dysbiosis through its metabolites.Conclusions: Lac has a remarkable antidepressant function, which it performs through the inhibition of dysbiosis (via its metabolites) and pattern recognition receptor TLR4 signaling.

Abnormal gut microbiota and bile acids in patients with first‐episode major depressive disorder and correlation analysis

“…Multiple clinical studies have found that probiotics could improve depression symptoms. [25][26][27][28] In animal studies, for instance, probiotics have also been found to improve depression-like behavior in rats and mice, [29][30][31][32] whereas others have found no difference between probiotics and placebos in improving depression symptoms. 33 Currently, more studies have shown that probiotics have a positive effect on depression symptoms, but the amount, type, and duration of probiotics in each study is inconsistent, and more studies are needed.…”

Lactobacillus paragasseri OLL2809 Improves Depression-Like Behavior and Increases Beneficial Gut Microbes in Mice

“…The combination of Lactobacillus and Bifidobacterium has an antidepressive effect when administered to rodents ( Arseneault-Bréard et al, 2012 ). A more recent report suggested that Lactobacillus suppresses inflammation, with decreases in toll-like receptor, NOD-like receptor and interleukin-1β, and exerts an antidepressant-like effect ( Qiu et al, 2021 ). Cytokines changes are well known to be implicated in the pathology of depression ( Himmerich et al, 2019 ).…”

“…A clinical study has showed that major depressive disorder patients have less Bifidobacterium or Lactobacillus ( Aizawa et al, 2016 ). In an experimental mouse lipopolysaccharide-induced depressive model, treatment with Lactobacillus delbrueckii inhibited depression-like behavior ( Qiu et al, 2021 ). Previous studies revealed that Lactobacillus paragasseri OLL2809 (formerly classified as L. gasseri ) ( Tanizawa et al, 2018 ) can induce an immune reaction ( Sashihara et al, 2006 ), and modulate anxiety and stress in young athletes ( Sashihara et al, 2013 ).…”

Novel Insights into the Role of Probiotics in Respiratory Infections, Allergies, Cancer, and Neurological Abnormalities

“…Inclusion of L. acidophilus and L. rhamnosus in the drinking water of the 5xFAD mice transiently increased Lactobacillaceae species without improving the nesting score but displayed reduced plaque load in the hippocampus [ 93 ]. In a similar mouse model, L. delbrueckii was described as able to improve depression-like behavior through inhibiting toll-like receptor 4 (TLR4) [ 94 ]…”