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Lactobacillus johnsonii BS15 Prevents Psychological Stress-Induced Memory Dysfunction in Mice by Modulating the Gut-Brain Axis.

ABSTRACT: Researchers are attempting to harness the advantages of the gut-brain axis to prevent neurocognitive disorders by enhancing intestinal health. In this study, four groups of ICR mice were orally gavaged with either phosphate-buffered saline (control and CW groups) or the probiotic strain Lactobacillus johnsonii BS15 (P and PW group; daily amounts of 2 × 108 colony-forming units) for 28 days. From days 22 to 28, the mice in the CW and PW groups were subjected to water-avoidance stress (WAS). The issue of whether psychological stress-induced memory dysfunction can be prevented via L. johnsonii BS15 pretreatment to modulate the gut-brain axis was investigated. Results show that L. johnsonii BS15 enhanced gut development by increasing villus height in the jejunum and ileum as well as villus height:crypt depth ratio in the ileum. L. johnsonii BS15 increased the activities of digestive enzymes, including trypsin and lipase in the jejunum and ileum. The intestinal goblet cell number was also increased by L. johnsonii BS15 pretreatment. Moreover, L. johnsonii BS15 balanced the gut microbiota by increasing the log10 DNA gene copies of Lactobacillus spp. and L. johnsonii and decreasing that of Enterobacteriaceae in the cecum. L. johnsonii BS15 also exerted preventive effects on intestinal permeability WAS by modulating diamine oxidase and D-lactate levels in the serum and mRNA expression levels of the tight junction proteins claudin-1, occludin, and ZO-1 in the jejunum and ileum. L. johnsonii BS15 pretreatment modulated inflammatory factors, specifically tumor necrosis factor-alpha, interferon-gamma, and interleukin-10. L. johnsonii BS15 pretreatment improved their performance in two behavioral tests, namely the novel object and T-maze tests. This result indicates that psychological stress-induced memory dysfunction possibly could be prevented through the gut-brain axis. In addition, L. johnsonii BS15 exerted beneficial effects on the hippocampus by modulating memory-related functional proteins, especially those related to synaptic plasticity, such as brain-derived neurotrophic factor and stem cell factor. Moreover, L. johnsonii BS15 recovered antioxidant capacity and exerted protective effects on mitochondrion-mediated apoptosis in the hippocampus. Collectively, the modulation of the gut-brain axis by L. johnsonii BS15 could be considered a promising non-invasive treatment modality for psychological stress-induced memory dysfunction.

SUBMITTER: Wang H

PROVIDER: S-EPMC7438410 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lactobacillus johnsonii BS15 Prevents Psychological Stress-Induced Memory Dysfunction in Mice by Modulating the Gut-Brain Axis.

Wang Hesong H Sun Ye Y Xin Jinge J Zhang Tao T Sun Ning N Ni Xueqin X Zeng Dong D Bai Yang Y

Frontiers in microbiology 20200813

Researchers are attempting to harness the advantages of the gut-brain axis to prevent neurocognitive disorders by enhancing intestinal health. In this study, four groups of ICR mice were orally gavaged with either phosphate-buffered saline (control and CW groups) or the probiotic strain Lactobacillus johnsonii BS15 (P and PW group; daily amounts of 2 × 108 colony-forming units) for 28 days. From days 22 to 28, the mice in the CW and PW groups were subjected to water-avoidance s ...[more]

PMID: 32903531

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Project description:BackgroundExcessive 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.MethodsMice 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.ResultsThe 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.ConclusionL. johnsonii BS15 intake could benefit the neuroinflammation and demyelination in the hippocampus by improving the gut environment and ameliorating fluorine-induced memory dysfunction.

Project description:The negative effects of ethanol (EtOH) abuse on the body have been widely reported in recent years. Building on the microbiota-gut-brain axis hypothesis, our study aimed to demonstrate the potential psychobiotic role of Lactobacillus johnsonii BS15 in the preventive effects of acute EtOH intake on memory impairment. We also determined whether L. johnsonii BS15 intake could effectively improve resistance to acute drinking and alleviate the adverse effects of EtOH. Male mice were fed L. johnsonii BS15 orally with (Probiotic group) or without (Control and Alcohol groups) daily dose of 0.2 × 109 CFU/ml per mouse for 28 days. Gavage with L. johnsonii BS15 significantly modified the ileal microbial ecosystem (assessed by 16S rRNA gene sequencing) in favor of Firmicutes and Lactobacillus, indicating the ability of BS15 to restore the gut microbiota. The acute EtOH exposure model (7 g/kg EtOH per mice) was established by gavage, which was administered to the alcohol and probiotic groups on day 28 of the experiment. The L. johnsonii BS15 intake effectively reduced alcohol unconsciousness time, blood alcohol concentration, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Meanwhile, the improvement of ethanol resistance time and the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were shown by BS15 in acute alcohol-induced mice. We found that acute EtOH exposure reduced the exploration ratio (assessed by the novel object recognition test), escape latency, number of errors (assessed by passive avoidance test), and spontaneous exploration (assessed by T-maze test) in mice, which were obviously improved by L. johnsonii BS15. In the hippocampus, L. johnsonii BS15 significantly reversed the decrease in antioxidant capacity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) and mRNA expression of memory-related functional proteins of brain-derived neurotrophic factor (BDNF) and cyclic ampresponse element binding protein (CREB) in the hippocampal tissue after acute EtOH exposure. In conclusion, L. johnsonii BS15 intake appears as a promising psychoactive therapy to ameliorate alcohol-mediated memory impairment by increasing EtOH metabolic levels.

Project description:Though the underlying mechanism remains elusive, a close relationship between psychological stress and intestinal inflammation has been widely accepted. Such a link is very important to set the basis for our understanding of the critical role of gut-brain axis (GBA) in homeostatic processes in health and disease. Probiotics that could confer benefits to mental health through GBA are referred to as "psychobiotics". This study aimed to further determine whether a potential psychobiotic strain, Lactobacillus johnsonii BS15 could prevent memory dysfunction in mice induced by psychological stress through modulating the gut environment, including intestinal inflammation and permeability. Memory dysfunction in mice was induced by restraint stress (RS), one of the most commonly utilized models to mimic psychological stress. The mice were randomly categorized into three groups including no stress (NS), restraint stress (RS), and probiotic (RS-P) and administered with either phosphate buffered saline (NS and RS groups) or L. johnsonii BS15 (RS-P group) every day from day 1-28. From days 22-28, the mice in RS and RS-P groups were subjected to RS each day. Results revealed that BS15-pretreatment enhanced the performance of RS-induced mice during three different behavioral tests for memory ability and positively modulated the hypothalamic-pituitary-adrenal axis by attenuating the serum corticosterone level. In the hippocampus, L. johnsonii BS15 positively modulated the memory-related functional proteins related to synaptic plasticity, increased neurotransmitter levels, and prevented RS-induced oxidative stress and mitochondria-mediated apoptosis. In the intestines, L. johnsonii BS15 protected the RS-induced mice from damaged gut barrier by enhancing the mRNA levels of tight junction proteins and exerted beneficial effects on the anti-inflammatory cytokine levels reduced by RS. These findings provided more evidence to reveal the psychoactive effect of L. johnsonii BS15 against memory dysfunction in RS-induced mice by modulating intestinal inflammation and permeability.

Project description:Numerous studies have focused on the beneficial effects of probiotics in animals. Even so, additional information should be obtained about the mechanisms by which a useful probiotic strain successfully exerts such beneficial effects. In this study, we evaluated the effect of the dietary supplementation of both live and disrupted Lactobacillus johnsonii (LJ) strain BS15 in broilers at different ages. Specifically, growth performance, lipid metabolism, gut microbiota, intestinal development, and digestive ability of the broilers were assessed. A total of 180 1-day-old Cobb 500 chicks were randomly distributed into three groups. These chicks were fed diets supplemented with 1 × 106 colony-forming units (cfu) LJ per gram of feed (LJ group); 1 × 106 cfu disrupted LJ per gram of feed (D-LJ group); and de Man, Rogosa, and Sharpe liquid medium (control group), respectively, throughout a 42-day experimental period. The results demonstrated that LJ supplementation of feed had a positive effect on the average daily gain and starter feed conversion ratio. In addition, LJ supplementation of feed decreased serum triglyceride and low-density lipid cholesterol levels, as well as abdominal fat deposition. LJ also reduced the mRNA levels of lipoprotein lipase in adipose tissue and stearoyl-CoA desaturase-1 in the liver. LJ diminished the mRNA quantities of the sterol regulatory element binding protein-1c and fatty acid synthase, as well as increased the level of serum high-density lipid cholesterol. LJ increased the mRNA quantities of peroxisome proliferator-activated receptor ?, acyl-CoA oxidase in the liver, and carnitine palmitoyltransferase-1. LJ also improved the intestinal development and digestive ability mainly by increasing the villus height/crypt depth ratio in the ileum. The probiotic increased the levels of epidermal growth factor and insulin-like growth factor-1, as well as the activities of trypsin and lipase in the jejunum and ileum. LJ exerted beneficial effects on the intestinal flora. Specifically, LJ markedly enhanced the population of Bacteroidetes and Lactobacillus spp. Moreover, the probiotic reduced the population of Enterobacteriaceae and the Firmicutes/Bacteroidetes ratio. Slight changes caused by disrupted LJ were detected. These findings indicated that live LJ supplementation may promote growth performance and lower fat deposition in broilers.

Dataset Information

Lactobacillus johnsonii BS15 Prevents Psychological Stress-Induced Memory Dysfunction in Mice by Modulating the Gut-Brain Axis.

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<i>Lactobacillus johnsonii</i> BS15 Prevents Psychological Stress-Induced Memory Dysfunction in Mice by Modulating the Gut-Brain Axis.

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