Exopolysaccharide is the potential effector of Lactobacillus fermentum PS150, a hypnotic psychobiotic strain.

Psychobiotics are a class of probiotics that confer beneficial effects on the mental health of the host. We have previously reported hypnotic effects of a psychobiotic strain, Lactobacillus fermentum PS150 (PS150), which significantly shortens sleep latency in experimental mice, and effectively ameliorate sleep disturbances caused by either caffeine consumption or a novel environment. In the present study, we discovered a L. fermentum strain, GR1009, isolated from the same source of PS150, and found that GR1009 is phenotypically distinct but genetically similar to PS150. Compared with PS150, GR1009 have no significant hypnotic effects in the pentobarbital-induced sleep test in mice. In addition, we found that heat-killed PS150 exhibited hypnotic effects and altered the gut microbiota in a manner similar to live bacteria, suggesting that a heat-stable effector, such as exopolysaccharide (EPS), could be responsible for these effects. Our comparative genomics analysis also revealed distinct genetic characteristics in EPS biosynthesis between GR1009 and PS150. Furthermore, scanning electron microscopy imaging showed a sheet-like EPS structure in PS150, while GR1009 displayed no apparent EPS structure. Using the phenol-sulfate assay, we found that the sugar content value of the crude extract containing EPS (C-EPS) from PS150 was approximately five times higher than that of GR1009, indicating that GR1009 has a lower EPS production activity than PS150. Through the pentobarbital-induced sleep test, we confirmed the hypnotic effects of the C-EPS isolated from PS150, as evidenced by a significant reduction in sleep latency and recovery time following oral administration in mice. In summary, we utilized a comparative approach to delineate differences between PS150 and GR1009 and proposed that EPS may serve as a key factor that mediates the observed hypnotic effect.

Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD. Here, the therapeutic efficacy of PS128 was examined in the 6-hydroxydopamine rat PD model. Suppression of the power spectral density of beta oscillations (beta PSD) in the primary motor cortex (M1) was recorded as the indicator of disease progression. We found that 6 weeks of daily PS128 supplementation suppressed M1 beta PSD as well as did levodopa and DBS. Long-term normalization of M1 beta PSD was found in PS128-fed rats, whereas levodopa and DBS showed only temporal effects. PS128 + levodopa and PS128 + DBS exhibited better therapeutic effects than did levodopa + DBS or either alone. Significantly improved motor functions in PS128-fed rats were correlated with normalization of M1 beta PSD. Brain tissue analyses further demonstrated the role of PS128 in dopaminergic neuroprotection and the enhanced availability of neurotransmitters. These findings suggest that psychobiotic PS128 might be used alongside conventional therapies to treat PD patients.

Lactobacillus paracasei PS23 improves cognitive deficits via modulating the hippocampal gene expression and the gut microbiota in D-galactose-induced aging mice.

Probiotic supplements are potential therapeutic agents for age-related cognitive deficits. A prior study showed that probiotic Lactobacillus paracasei PS23 (PS23) supplementation delayed age-related cognitive decline in mice. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of live or heat-killed PS23 (HK-PS23) on cognitive function in D-galactose (D-gal)-induced aging mice and explore the underlying mechanisms. We designed four groups of mice: control, D-gal aging mice, and PS23 supplemented and HK-PS23 supplemented D-gal aging mice. We evaluated memory function and anxiety using Morris water maze and open field tests, respectively. Neural monoamines and activities of superoxide dismutase (SOD) in the hippocampus were evaluated. RNA-seq was used to evaluate hippocampal gene expression profiles in each group, and the composition of the gut microbiota was analyzed. We revealed that PS23 and HK-PS23 supplementation ameliorated D-gal-induced memory deficits and improved motor and anxiety-behaviors in aging mice. In the hippocampus, serotonin levels (5-HT) were increased and the genes involved in neuroplasticity, anti-inflammatory, and antioxidant functions were upregulated in PS23 and HK-PS23 supplemented groups. The gut microbiota showed specific changes. Our results suggest that PS23 and HK-PS23 supplements could ameliorate age-related cognitive decline, possibly by upregulating the genes involved in synaptic plasticity and preventing oxidation and inflammation.

Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice.

Lactobacillus plantarum PS128 has been reported as a psychobiotic to improve mental health through the gut-brain axis in experimental animal models. To explore its mechanism of action in the gut, this study aimed to analyze the effects of L. plantarum PS128 ingestion on naïve and loperamide (Lop)-induced constipation mice. We found that, in the two mouse models, the weight, number, and water content of feces in the L. plantarum PS128 group were higher than those in the vehicle control group. Histological observation revealed that L. plantarum PS128 increased the level of colonic mucins including the major mucin MUC2. In addition, the charcoal meal test showed that L. plantarum PS128 significantly increased the small intestine transit in naïve mice, but not in the Lop-treated mice. Since intestinal serotonin has been found to modulate motility, we further analyzed the expression of genes related to serotonin signal transduction in the small intestine of naïve mice. The results showed that L. plantarum PS128 significantly altered the expression levels of Tph1, Chga, Slc6a4, and Htr4, but did not affect the expression levels of Tph2, Htr3a, and Maoa. Furthermore, immunohistochemistry revealed that L. plantarum PS128 significantly increased the number of serotonin-containing intestinal cells in mice. Taken together, our results suggest that L. plantarum PS128 could promote intestinal motility, mucin production, and serotonin signal transduction, leading to a laxative effect in mice.

Hypnotic Effects of Lactobacillus fermentum PS150TM on Pentobarbital-Induced Sleep in Mice.

The bidirectional communication between the gastrointestinal tract and the central nervous system appears to be functionally linked to the intestinal microbiome, namely the microbiome-gut-brain axis (MGBA). Probiotics with health benefits on psychiatric or neurological illnesses are generally called psychobiotics, and some of them may also be able to improve sleep by targeting the MGBA. This study aimed to investigate the effects of a psychobiotic strain, Lactobacillus fermentum PS150TM (PS150TM), on sleep improvement by using a pentobarbital-induced sleep mouse model. Compared with the vehicle control group, the oral administration of PS150TM, but not the other L. fermentum strains, significantly decreased the sleep latency and increased the sleep duration of mice, suggesting strain-specific sleep-improving effects of PS150TM. Moreover, the ingestion of diphenhydramine, an antihistamine used to treat insomnia, as a drug control group, only increased the sleep duration of mice. We also found that the sleep-improving effects of PS150TM are time- and dose-dependent. Furthermore, the oral administration of PS150TM could attenuate a caffeine-induced sleep disturbance in mice, and PS150TM appeared to increase the expression of the gene encoding the adenosine 1 receptor in the hypothalamus of mice, as assessed by quantitative real-time polymerase chain reaction. Taken together, our results present a potential application of PS150TM as a dietary supplement for sleep improvement.

Transcriptomic gene-network analysis of exposure to silver nanoparticle reveals potentially neurodegenerative progression in mouse brain neural cells.

Silver nanoparticles (AgNPs) are commonly used in daily living products. AgNPs can induce inflammatory response in neuronal cells, and potentially develop neurological disorders. The gene networks in response to AgNPs-induced neurodegenerative progression have not been clarified in various brain neural cells. This study found that 3-5nm AgNPs were detectable to enter the nuclei of mouse neuronal cells after 24-h of exposure. The differentially expressed genes in mouse brain neural cells exposure to AgNPs were further identified using Phalanx Mouse OneArray® chip, and permitted to explore the gene network pathway regulating in neurodegenerative progression according to Cytoscape analysis. In focal adhesion pathway of ALT astrocytes, AgNPs induced the gene expression of RasGRF1 and reduced its downstream BCL2 gene for apoptosis. In cytosolic DNA sensing pathway of microglial BV2 cells, AgNPs reduced the gene expression of TREX1 and decreased IRF7 to release pro-inflammatory cytokines for inflammation and cellular activation. In MAPK pathway of neuronal N2a cells, AgNPs elevated GADD45α gene expression, and attenuated its downstream PTPRR gene to interfere with neuron growth and differentiation. Moreover, AgNPs induced beta amyloid deposition in N2a cells, and decreased PSEN1 and PSEN2, which may disrupt calcium homeostasis and presynaptic dysfunction for Alzheimer's disease development. These findings suggested that AgNPs exposure reveals the potency to induce the progression of neurodegenerative disorder.

Silver nanoparticles affect on gene expression of inflammatory and neurodegenerative responses in mouse brain neural cells.

Silver nanoparticles (AgNPs) have antibacterial characteristics, and currently are applied in Ag-containing products. This study found neural cells can uptake 3-5 nm AgNPs, and investigated the potential effects of AgNPs on gene expression of inflammation and neurodegenerative disorder in murine brain ALT astrocytes, microglial BV-2 cells and neuron N2a cells. After AgNPs (5, 10, 12.5 µg/ml) exposure, these neural cells had obviously increased IL-1ß secretion, and induced gene expression of C-X-C motif chemokine 13 (CXCL13), macrophage receptor with collagenous structure (MARCO) and glutathione synthetase (GSS) for inflammatory response and oxidative stress neutralization. Additionally, this study found amyloid-ß (Aß) plaques for pathological feature of Alzheimer's disease (AD) deposited in neural cells after AgNPs treatment. After AgNPs exposure, the gene expression of amyloid precursor protein (APP) was induced, and otherwise, neprilysin (NEP) and low-density lipoprotein receptor (LDLR) were reduced in neural cells as well as protein level. These results suggested AgNPs could alter gene and protein expressions of Aß deposition potentially to induce AD progress in neural cells. It's necessary to take notice of AgNPs distribution in the environment.