Lactobacillus johnsonii BS15 improves intestinal environment against fluoride-induced memory impairment in mice—a study based on the gut–brain axis hypothesis

Abstract

Background Excessive fluoride can lead to chronic neurodegeneration characterized by neuron and myelin loss and memory dysfunction. The gut–brain axis hypothesis suggests that gut microbiota plays a crucial role in regulating brain function. Thus, using probiotics to adjust the gut microenvironment may be a potential therapy for mental diseases. Methods Mice in the prob group were administrated with Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70-day exposure to sodium fluoride. The drinking water of all groups (F and prob groups) except the control group were replaced by high-fluoride water (100 mg NaF/L) on day 28. Animals in each group were divided into two subsets: one underwent behavioral test, and the other was sacrificed for sampling. The mRNA expression level and protein content related to inflammatory reaction in the ileum and hippocampus were respectively detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of proteins related to myelin structure, apoptosis, and memory in the hippocampus and tight junction proteins in the ileum were determined by RT-qPCR and/or immunohistochemistry. Gut permeability markers (D-lactate and diamine oxidase (DAO)) in the serum were also examined by ELISA. Results The results showed that fluoride exposure induced a lower spontaneous exploration (P < 0.05) in T-maze test, which indicated an impairment of memory. Spontaneous exploration of BS15-treated mice was significantly higher (P < 0.05) than that in F group. Fluoride reduced (P < 0.05) levels of myelin structural protein (proteolipid protein) and neurogenesis-associated proteins (brain-derived neurotrophic factor and cAMP/Ca2+ responsive element-binding protein), induced disordered inflammatory cytokines (TNF-α, IFN-γ, and IL-6; P < 0.05), increased pro-apoptotic genes (caspase-3; P < 0.05), and decreased anti-apoptotic genes (Bcl-2; P < 0.05) in the hippocampus, of which the influences were reversed by BS15. BS15 treatment exerted significant preventive effects on reversing the gut inflammation induced by excessive fluoride intake by reducing (P < 0.05) the levels of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) and remarkably increasing (P < 0.05) the level of anti-inflammatory cytokines (IL-10). Moreover, the serum DAO activity and D-lactate concentration significantly increased by fluoride were also reduced (P < 0.05) by BS15. This result indicated the profitable effect of BS15 on gut permeability. Conclusion L. johnsonii BS15 intake could benefit the neuroinflammation and demyelination in the hippocampus by improving the gut environment and ameliorating fluorine-induced memory dysfunction.

Psychoactive Effects of Lactobacillus johnsonii BS15 on Preventing Memory Dysfunction Induced by Acute Ethanol Exposure Through Modulating Intestinal Microenvironment and Improving Alcohol Metabolic Level

“…Notably, the behavioral performance of mice with acute alcohol intake was significantly ameliorated by BS15 pretreatment; thus, the positive effects of L. johnsonii BS15 prove it as a potentially beneficial bacterium. The changes in the behavioral tests induced by L. johnsonii BS15 pretreatment were consistent with the conclusions of our earlier research (Sun et al, 2020;Xin et al, 2020;Wang et al, 2021).…”

“…Our study also verified the preventative influence of L. johnsonii BS15 on drunkenness. The normal animal memory level relies upon a delicate change in the intestinal flora, organizational barrier, and circulation system (Sun et al, 2020;Xin et al, 2020Xin et al, , 2021aWang et al, 2021). Although various factors, such as neuroinflammation, lipid peroxidation, autophagy, and apoptosis, can affect brain health, the gut microbiome plays a significant role as one of the main drivers.…”

Lactobacillus johnsonii 6084 alleviated sepsis‐induced organ injury by modulating gut microbiota

“…For instance, L. johnsonii BS15 can attenuate inflammation in obese mice (Xin et al, 2014 ); L. johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis (Soriano et al, 2012 ). L. johnsonii BS15 intake benefits the neuroinflammation and demyelination in the hippocampus (Xin et al, 2020 ). Similarly, we observed that L. johnsonii decreased the level of inflammatory factors in an LPS‐induced sepsis mouse model.…”

Sodium Butyrate Ameliorates Fluorosis-Induced Neurotoxicity by Regulating Hippocampal Glycolysis In Vivo

“…All animals were fed standard food in the laboratory, and the laboratory temperature was set to 21-24°C, the humidity to 50 ± 5%, and the light and dark cycle to 12 h. After one week of adaptation, the mice were randomly divided into ve groups: a control group (C), uorosis group (F), sodium butyrate group (S), uorosis and 500 mg/kg sodium butyrate treatment group (F + S1), and uorosis and 1000 mg/kg sodium butyrate treatment group (F + S2), with 10 mice in each group. According to the previous literature, 100mg/L sodium uoride can cause brain damage in mice [9,31,32]. Except for groups C and S, all groups were provided with distilled water containing 100 mg/L uoride (Sigma-Aldrich, St. Louis, MO, USA).…”