Investigating the impact of probiotic on neurological outcomes in Rett syndrome: A randomized, double-blind, and placebo-controlled pilot study.

LAY ABSTRACT: Rett syndrome often involves gastrointestinal symptoms and gut microbiota imbalances. We conducted a study to explore the feasibility of probiotic Lactobacillus plantarum PS128 and the impact on neurological functions in Rett syndrome. The results of our investigation demonstrated that the supplementation of probiotic L. plantarum PS128 was feasible and well tolerated, with 100% retention rate and 0% withdrawal rate. In addition, there was only one participant who had loose stool after taking L. plantarum PS128. Further, there was a tendency to enhance overall cognitive developmental level, as assessed using Mullen Scales of Early Learning. In addition, it significantly improved dystonia, as assessed using the Burke-Fahn-Marsden Movement Scale, in comparison with the placebo group. This study provides a strong foundation for future research and clinical trials exploring the potential of L. plantarum PS128 probiotics as a complementary therapy for individuals with Rett syndrome.

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.

Neuroprotective Effects of Lactobacillus plantarum PS128 in a Mouse Model of Parkinson's Disease: The Role of Gut Microbiota and MicroRNAs.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of Lactobacillus plantarum PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them, Bifidobacterium, Ruminiclostridium_6, Bacteroides, and Alistipes were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice.

Dynamic prevalence of sleep disturbance among critically ill patients in intensive care units and after hospitalisation: A systematic review and meta-analysis.

BACKGROUND: Sleep disturbance is a common complaint among critically ill patients in intensive care units and after hospitalisation. However, the prevalence of sleep disturbance among critically ill patients varies widely. OBJECTIVE: To estimate the prevalence of sleep disturbance among critically ill patients in the intensive care unit and after hospitalisation. METHODS: Electronic databases were searched from their inception until 15 August 2022. Only observational studies with cross-sectional, prospective, and retrospective designs investigating sleep disturbance prevalence among critically ill adults (aged ≥ 18 years) during intensive care unit stay and after hospitalisation were included. RESULTS: We found 13 studies investigating sleep disturbance prevalence in intensive care units and 14 investigating sleep disturbance prevalence after hospitalisation, with 1,228 and 3,065 participants, respectively. The prevalence of sleep disturbance during an ICU stay was 66 %, and at two, three, six and ≥ 12 months after hospitalisation was 64 %, 49 %, 40 %, and 28 %, respectively. Studies using the Richards-Campbell Sleep Questionnaire detected a higher prevalence of sleep disturbance among patients in intensive care units than non-intensive care unit specific questionnaires; studies reported comparable sleep disturbance prevalence during intensive care stays for patients with and without mechanical ventilation. CONCLUSION: Sleep disturbance is prevalent in critically ill patients admitted to an intensive care unit and persists for up to one year after hospitalisation, with prevalence ranging from 28 % to 66 %. The study results highlight the importance of implementing effective interventions as early as possible to improve intensive care unit sleep quality.

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 paragasseri BBM171 Ameliorates Allergic Airway Inflammation Induced by Ovalbumin in Mice via Modulating the Th1/Th2 Balance

Supplementation with specific probiotics has been shown to improve allergic airway symptoms. This study aimed to investigate immunomodulatory effects of a potential probiotic strain isolated from breast milk, Lactobacillus paragasseri BBM171 (BBM171), in an ovalbumin (OVA)-induced allergic mouse model. OVA-sensitized and OVA-challenged BALB/c mice were orally administered live or heat-inactivated BBM171 for 48 consecutive days. After the last allergen challenge, serum immunoglobulin (Ig) levels, inflammatory cell levels in the lungs, and cytokine levels in bronchoalveolar lavage fluid (BALF) were assessed. The results showed that oral administration of live or heat-inactivated BBM171 decreased serum levels of total IgE, OVA-specific IgE, and OVA-specific IgG1, while increasing OVA-specific IgG2a and reducing the extent of airway inflammation in OVA-induced allergic mice. In addition, both live and heat-inactivated BBM171 modulated the cytokine profile in BALF to a type 1 T helper (Th1) response. Furthermore, ex vivo experiments using OVA-induced allergic mouse splenocytes showed that both live and heat-inactivated BBM171 could regulate the Th1/Th2 balance, decrease the proinflammatory cytokine interleukin (IL)-17 level, and increase the anti-inflammatory cytokine IL-10 level. Taken together, these results suggest that oral administration of live or heat-inactivated BBM171 improved allergen-induced airway inflammation symptoms by modulating the host immune response toward Th1 dominance.

Psychobiotic supplementation of HK-PS23 improves anxiety in highly stressed clinical nurses: a double-blind randomized placebo-controlled study.

Nurses often experience adverse health effects associated with increasing levels of work-related stress. Stress may induce systemic effects through the HPA axis, glucocorticoid responses, and inflammatory cascades. Psychobiotics may help alleviate stress through associations of the microbiota, anti-inflammation factors, and the gut-brain axis. We aimed to investigate whether interventions with a psychobiotic, heat-killed (HK)-PS23 cells, may help improve perceived stress, anxiety, and related biological markers among highly stressed clinical nurses. This double-blind, randomized, placebo-controlled study included seventy clinical nurses from a medical center in Northern Taiwan who scored 27 or higher on the 10-item version of the Perceived Stress Scale (PSS), and participants were randomized into either taking HK-PS23 or a placebo for 8 weeks. Baseline and endpoint results of the PSS, Job Stress Scale, State and Trait Anxiety Index (STAI), emotional questionnaires, gastrointestinal severity questionnaires, Trails Marking Tests, blood biological markers, and sleep data were analyzed. While both groups demonstrated improvements in most measures over time, only the blood cortisol measure demonstrated significant group differences after the 8-week trial. Further analyses of the subgroup with higher anxiety (nurses with STAI ≥ 103) revealed that anxiety states had improved significantly in the HK-PS23 group but not in the placebo group. In summary, this placebo-controlled trial found significant reduction in the level of blood cortisol after 8 weeks of HK-PS23 use. The distinctive anxiolytic effects of HK-PS23 may be beneficial in improving perceived anxiety and stress hormone levels in female nurses under pressure. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT04452253-sub-project 1.

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.

Safety Evaluation and Anti-Inflammatory Efficacy of Lacticaseibacillus paracasei PS23.

Lacticaseibacillus paracasei strain PS23 (PS23) exhibits some probiotic properties. In this study, a genomic analysis of PS23 revealed no genes related to virulence or antibiotic resistance. Moreover, ornithine decarboxylase activity was not detected in vitro. In addition, PS23 was sensitive to the tested antibiotics. Genotoxicity tests for PS23 including the Ames test and chromosomal aberrations in vitro using Chinese hamster ovary cells and micronuclei in immature erythrocytes of ICR mice were all negative. Moreover, following a 28-day study involving repeated oral dose toxicity tests (40, 400, and 4000 mg/kg equal 1.28 × 1010, 1.28 × 1011, and 1.28 × 1012 CFU/kg body weight, respectively) using an ICR mouse model, no adverse effects were observed from any doses. In addition, supplementation with live or heat-killed PS23 ameliorates DSS-induced colonic inflammation in mice. Our findings suggest that PS23 is safe and has anti-inflammatory effects and may therefore have therapeutic implications.

Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome.

Tourette syndrome results from a complex interaction between social-environmental factors, multiple genetic abnormalities, and neurotransmitter disturbances. This study is a double-blinded, randomized controlled trial using probiotics Lactobacillus plantarum PS128 as an intervention to examine if probiotics improve symptoms of children with Tourette syndrome. This study enrolled children aged 5 to 18 years old who fulfilled DSM-V diagnostic criteria for Tourette syndrome. Patients were assessed before initiating the trial, at one month, and at two months after randomization. The primary outcome was evaluated by Yale Global Tic Severity Scale (YGTSS), and the secondary outcome studied the possible comorbidities in these children. The results revealed no significant difference in improvement in YGTSS between the control group and the PS128 group. As for secondary endpoints, an analysis of Conners' Continuous Performance Test (CPT) showed improvement in commission and detectability in the PS128 group. In conclusion, although probiotics may not have tic-reducing effects in children with Tourette syndrome, it may have benefits on comorbidities such as attention deficit and hyperactivity disorder (ADHD). Further studies are needed to clarify the effects of probiotics on the comorbidities of Tourette syndrome children.

Effect of Daily Oral Lactobacillus plantarum PS128 on Exercise Capacity Recovery after a Half-Marathon.

A half-marathon (HM) is a vigorous high-intensity exercise, which could induce lower extremity musculoskeletal injury risks for recreational runners. They usually consume nonsteroidal anti-inflammatory drugs (NSAIDs) in order to shorten their return to play but ignore the side effects, such as peptic ulcers and renal and vascular disorders. Lactobacillus plantarum PS128 (PS128) could improve inflammation and oxidative stress by modulating the gut microbiota, thus potentially improving muscle damage and recovery. However, few studies have addressed the PS128 exercise capacity recovery 96 h after HM. Thus, this study aimed to investigate the effect of PS128 on exercise capacity and physiological adaptation after HM. A double-blind, randomized, placebo-controlled, counterbalanced, crossover trial was used for the experiment. HM was conducted at the beginning and end of the 4-week nutritional supplement administration. Eight recreational runners took two capsules (3 × 1010 CFU/capsule) of PS128 each morning and evening before meals for 4 weeks as the PS128 treatment (LT), or they took two capsules of placebo for 4 weeks as the placebo treatment (PT). In both treatments, an exercise capacity test (lower extremity muscle strength, anaerobic power, lower extremity explosive force, and aerobic capacity) and blood test (muscle fatigue, muscle damage, oxidative stress, and renal injury) were performed before the administration of the nutritional supplement (baseline), 48 h before HM (pre), and 0 h (0 h post), 3 h (3 h post), 24 h (24 h post), 48 h (48 h post), 72 h (72 h post), and 96 h (96 h post) after HM. There was no significant difference in the total duration of HM between PT and LT, but PT was found to be significantly higher than LT at Stage 4 (15,751-21,000 m) of HM (3394 ± 727 s vs. 2778 ± 551 s, p = 0.02). The lower extremity muscle strength measured using an isokinetic dynamometer in PT was significantly lower than that in LT at 72 h after HM. The lower extremity explosive force from the countermovement jump (CMJ) in PT was significantly decreased compared to 24 h prior. There was no significant difference between anaerobic power and aerobic capacity between the two treatments after HM. After HM, LT had lower muscle damage indices, such as myoglobin (3 h post-PT vs. -LT: 190.6 ± 118 ng/mL vs. 91.7 ± 68.6 ng/mL, p < 0.0001) and creatine phosphokinase (24 h post-PT vs. -LT: 875.8 ± 572.3 IU/L vs. 401 ± 295.7 IU/L, p < 0.0001). Blood urea nitrogen recovered in 24 h (24 h pre- vs. post-LT, p > 0.05) and higher superoxide dismutase was found in LT (96 h post-PT vs. -LT: 0.267 ± 0.088 U/mL vs. 0.462 ± 0.122 U/mL, p < 0.0001). In conclusion, PS128 supplementation was associated with an improvement in muscle damage, renal damage, and oxidative stress caused by HM through microbiota modulation and related metabolites but not in exercise capacity.

Coculture Strategy for Developing Lactobacillus paracasei PS23 Fermented Milk with Anti-Colitis Effect.

Few studies have documented the effects of fermented milk on intestinal colitis, which are mediated by regulating various microbial and inflammatory processes. Here, we investigated the effects of fermented milk with Lactobacillus paracasei PS23 on intestinal epithelial cells in vitro and dextran sulfate sodium (DSS)-induced colitis in vivo. As L. paracasei PS23 grew poorly in milk, a coculture strategy with yogurt culture was provided to produce fermented milk (FM). The results indicated that the coculture exhibited a symbiotic effect, contributing to the better microbial and physicochemical property of the fermented milk products. We further evaluated the anti-colitis effect of fermented milk with L. paracasei PS23 in vitro. Both PS23-fermented milk (PS23 FM) and its heat-killed counterpart (HK PS23 FM) could protect or reverse the increased epithelial permeability by strengthening the epithelial barrier function in vitro by increasing transepithelial electrical resistance (TEER). In vivo analysis of the regulation of intestinal physiology demonstrated that low-dose L. paracasei PS23-fermented ameliorated DSS-induced colitis, with a significant attenuation of the bleeding score and reduction of fecal calprotectin levels. This anti-colitis effect may be exerted by deactivating the inflammatory cascade and strengthening the tight junction through the modification of specific cecal bacteria and upregulation of short-chain fatty acids. Our findings can clarify the role of L. paracasei PS23 in FM products when cocultured with yogurt culture and can elucidate the mechanisms of the anti-colitis effect of L. paracasei PS23 FM, which may be considered for therapeutic intervention.

Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer's disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis.

BACKGROUND: According to recent evidence, psychobiotics exert beneficial effects on central nervous system-related diseases, such as mental disorders. Lactobacillus plantarum PS128 (PS128), a novel psychobiotic strain, improves motor function, depression, and anxiety behaviors. However, the psychobiotic effects and mechanisms of PS128 in Alzheimer's disease (AD) remain to be explored. OBJECTIVES: The goal of the current study was to evaluate the beneficial effects of PS128 and to further elucidate its mechanism in AD mice. METHODS: PS128 (1010 colony-forming unit (CFU)/ml) was administered via oral gavage (o.g.) to 6-month-old male wild-type B6 and 3 × Tg-AD mice (harboring the PS1M146V, APPswe and TauP30IL transgenes) that received an intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg) or vehicle (saline) for 33 days. After serial behavioral tests, fecal short-chain fatty acid levels and AD-related pathology were assessed in these mice. RESULTS: Our findings show that intracerebroventricular injection of streptozotocin accelerated cognitive dysfunction associated with increasing levels of glycogen synthase kinase 3 beta (GSK3ß) activity, tau protein phosphorylation at the T231 site (pT231), amyloid-ß (Aß) deposition, amyloid-ß protein precursor (AßPP), ß-site AßPP-cleaving enzyme (BACE1), gliosis, fecal propionic acid (PPA) levels and cognition-related neuronal loss and decreasing postsynaptic density protein 95 (PSD95) levels in 3 × Tg-AD mice. PS128 supplementation effectively prevented the damage induced by intracerebroventricular injection of streptozotocin in 3 × Tg-AD mice. CONCLUSIONS: Based on the experimental results, intracerebroventricular injection of streptozotocin accelerates the progression of AD in the 3 × Tg-AD mice, primarily by increasing the levels of gliosis, which were mediated by the propionic acid and glycogen synthase kinase 3 beta pathways. PS128 supplementation prevents damage induced by intracerebroventricular injection of streptozotocin by regulating the propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis in 3 × Tg-AD mice. Therefore, we suggest that PS128 supplementation is a potential strategy to prevent and/or delay the progression of AD.

Lactobacillus fermentum PS150 promotes non-rapid eye movement sleep in the first night effect of mice.

The first night effect (FNE) is a type of sleep disturbance caused by an unfamiliar environment, which leads to difficulty falling asleep and reduced sleep duration. Previously, we reported that Lactobacillus fermentum PS150 (PS150) improves sleep conditions in a pentobarbital-induced sleep mouse model. In this study, we aimed to evaluate the effect of PS150 on the FNE in mice. Briefly, mice were implanted with electrodes and orally administered PS150 for four weeks, and then the FNE was induced by cage changing. Analysis of polysomnographic signals revealed that intervention with PS150 restored non-rapid eye movement (NREM) sleep length under the FNE. Compared to diphenhydramine, a commonly used sleep aid, PS150 had no unwanted side effects, such as rapid eye movement (REM) sleep deprivation and fragmented sleep. Moreover, temporal analysis revealed that PS150 efficiently reduced both sleep latency and time spent restoring normal levels of REM sleep. Taken together, these results suggest that PS150 efficiently ameliorates sleep disturbance caused by the FNE. Additionally, V3-V4 16S rRNA sequencing revealed significant increases in Erysipelotrichia, Actinobacteria, and Coriobacteriia in fecal specimens of the PS150-treated group, indicating that PS150 induces gut microbiota remodeling.

Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial.

Recent animal studies have supported that Lactobacillus plantarum PS128 (PS128) can reduce the severity of anxiety and depression. However, previous studies did not focus on the sleep quality and mood of humans. This study determines whether PS128 reduces the severity of anxiety and depressive symptoms, regulates autonomic nervous system function, and improves sleep quality. Forty participants between 20 and 40 years of age with self-reported insomnia were randomly assigned to two groups, a PS128 group and a placebo group, in a double-blind trial. Participants took two capsules of either PS128 or a placebo after dinner for 30 days. Study measures included subjective depressive symptoms, anxiety and sleep questionnaires, and miniature-polysomnography recordings at baseline and on the 15th and 30th days of taking capsules. Overall, all outcomes were comparable between the two groups at baseline and within the 30-day period, yet some differences were still found. Compared to the control group, the PS128 group showed significant decreases in Beck Depression Inventory-II scores, fatigue levels, brainwave activity, and awakenings during the deep sleep stage. Their improved depressive symptoms were related to changes in brain waves and sleep maintenance. These findings suggest that daily administration of PS128 may lead to a decrease in depressive symptoms, fatigue level, cortical excitation, and an improvement in sleep quality during the deep sleep stage. Daily consumption of PS128 as a dietary supplement may improve the depressive symptoms and sleep quality of insomniacs, although further investigation is warranted.

The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study.

Background: Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis. Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient "ON-OFF" diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures. Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52-72), mean disease duration was 10.12 ± 2.3 years (range, 5-14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675-1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels. Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT04389762.

Psychobiotic Supplementation of PS128TM Improves Stress, Anxiety, and Insomnia in Highly Stressed Information Technology Specialists: A Pilot Study.

Background: Information technology (IT) is an industry related to the production of computers, information processing, and telecommunications. Such industries heavily rely on the knowledge and solutions provided by IT specialists. Previous reports found that the subjective stress scores were higher in IT specialists who developed diabetes, hypertension, and depression. Specific probiotics, known as psychobiotics, may alleviate stress and mood symptoms. This study aimed to examine whether an 8-week intervention of a novel psychobiotic, Lactobacillus plantarum PS128TM (PS128TM), improved self-perceived stress and mood symptoms among high-stress IT specialists. Methods: This open-label, single-arm, baseline-controlled study included IT specialists from a large IT company in Northern Taiwan. Participants with a Perceived Stress Scale (PSS) 10-item version score of 27 or higher were included. Participants were asked to take two capsules containing PS128TM powder, equivalent to 20 billion colony-forming units, daily. Self-report measures, such as the Job Stress Scale, Visual Analog Scale of Stress, the Insomnia Severity Index, the State and Trait Anxiety Index, the Questionnaire for Emotional Trait and State, the Patient Health Questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire, and Gastrointestinal Severity Index were compared at baseline and at the end of the trial period. The primary outcome was a 20% reduction in the PSS score at endpoint. Objective measures included salivary levels of stress biomarkers, including cortisol, α-amylase, immunoglobulin A, lactoferrin, and lysozymes, as well as results of the Test of Attentional Performance. Results: Of the 90 eligible IT specialists, 36 met the inclusion criteria. After the 8-week trial period, significant improvements in self-perceived stress, overall job stress, job burden, cortisol level, general or psychological health, anxiety, depression, sleep disturbances, quality of life, and both positive and negative emotions were found. Conclusion: Our results suggest that PS128TM has the distinct advantage of providing stress relief and can improve mental health for people with a high-stress job. Future placebo-controlled studies are warranted to explore the effect and underlying mechanisms of action of PS128TM. Clinical Trial Registration: https://clinicaltrials.gov/ (identifier: NCT04452253-sub-project 2).

Gerobiotics: probiotics targeting fundamental aging processes.

Aging is recognized as a common risk factor for many chronic diseases and functional decline. The newly emerging field of geroscience is an interdisciplinary field that aims to understand the molecular and cellular mechanisms of aging. Several fundamental biological processes have been proposed as hallmarks of aging. The proposition of the geroscience hypothesis is that targeting holistically these highly integrated hallmarks could be an effective approach to preventing the pathogenesis of age-related diseases jointly, thereby improving the health span of most individuals. There is a growing awareness concerning the benefits of the prophylactic use of probiotics in maintaining health and improving quality of life in the elderly population. In view of the rapid progress in geroscience research, a new emphasis on geroscience-based probiotics is in high demand, and such probiotics require extensive preclinical and clinical research to support their functional efficacy. Here we propose a new term, "gerobiotics", to define those probiotic strains and their derived postbiotics and para-probiotics that are able to beneficially attenuate the fundamental mechanisms of aging, reduce physiological aging processes, and thereby expand the health span of the host. We provide a thorough discussion of why the coining of a new term is warranted instead of just referring to these probiotics as anti-aging probiotics or with other similar terms. In this review, we highlight the needs and importance of the new field of gerobiotics, past and currently on-going research and development in the field, biomarkers for potential targets, and recommended steps for the development of gerobiotic products. Use of gerobiotics could be a promising intervention strategy to improve health span and longevity of humans in the future.

A Meta-analysis of Dynamic Prevalence of Cognitive Deficits in the Acute, Subacute, and Chronic Phases After Traumatic Brain Injury.

ABSTRACT: BACKGROUND: Reports regarding prevalence of post-traumatic brain injury (TBI) cognitive deficits were inconsistent. We aimed to synthesize the prevalence of cognitive deficits after TBI in the acute, subacute, and chronic phases. METHODS: PubMed, EMBASE, and ProQuest Dissertations and Theses A&I databases were searched from the inception to April 27, 2020. Studies with prospective, retrospective, and cross-sectional designs reporting the prevalence of cognitive deficits after TBI in adults were included. RESULTS: A total of 15 articles were included for prevalence estimation. The pooled prevalence of memory and attention deficits after mild TBI was 31% and 20% in the acute phase and 26% and 18% in the subacute phase, respectively, and 49% and 54% in the subacute phase and 21% and 50% in the chronic phase after moderate-to-severe TBI. The overall prevalence of information processing speed deficits after mild TBI in the acute and subacute phases was 21% and 17%, respectively, and 57% in the chronic phase after moderate-to-severe TBI. The overall prevalence of executive dysfunction in the subacute and chronic phases was 48% and 38%, respectively, after moderate-to-severe TBI. CONCLUSION: Cognitive deficits are prevalent in the acute to chronic phases after TBI. Healthcare providers should design effective intervention targeting cognitive impairment after TBI as early as possible.