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Effect of Lactobacillus plantarum PS128 (PS128) on visceral hypersensitivity (VH). The visceromotor reflex was measured 30 min before (baseline) and after 5-hydroxytryptophan (5-HTP) injection for rats oral administration with saline for 14 days (Saline) (a) and rats received Lactobacillus plantarum PS128 (PS128) for 14 days (b). ***P < 0.001; **P < 0.01, versus baseline by repeated 2-way ANOVA with Bonferroni correction
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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Current treatments for IBS are unsatisfactory due to its multifactorial pathogenesis involving the microbiota–gut–brain axis. Lactobacillus plantarum PS128 (PS128) was reported to exhibit neuromodulatory a...
Citations
... L. plantarum PS128 was found to inhibit the 5-hydroxytryptophan-induced visceral hypersensitivity during colorectal distention, the effect followed by decreased serum corticosterone, decreased neurotransmitter protein [substance P, CGRP, BDNF, and NGF] in the spinal cord, and increase of the glucocorticoid receptor and decrease of mineralocorticoid receptor in the amygdala. These findings suggest that L. plantarum PS128 decreased splanchnic hypersensitivity through modulating the gut-brain axis and the HPA axis [156]. ...
Post-operative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall, and the splanchnic pain, induced by the activation of nociceptors of the viscera, which are highly sensi-tive to distension, ischemia and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly af-fected by both anaesthesia and surgical manipulation. Thus, efforts to restore the disturbed micro-biome by supplementation with beneficial bacteria, namely probiotics, seems to be effective. In this article the knowledge gained mainly from experimental research on this topic is analyzed, the con-cluding message being that each probiotic strain works in its own way towards pain relief.
... Lactobacillus plantarum PS128 is a novel psychobiotic that alleviates depression-and anxiety-like behaviors [10, Chih-Ming Chen and Chien-Chen Wu contributed equally to this study. 11], visceral hypersensitivity [12], and neurobehavioral aspects of movement disorders [13,14] in experimental animals. Clinically, L. plantarum PS128 appears to ameliorate the opposition/defiance behaviors in children with ASD [15], enhance exercise performance in triathletes [16], and improve self-perceived stress and salivary cortisol levels in highly stressed information technology specialists [17]. ...
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.
... PS128 was prescribed for dogs at the dosage of 1 × 10 9 CFU/kg (equal to 0.02 g/kg) once a day for a course of 14 days. The dosage was chosen referring to the previous studies in mice (Liu et al., 2016a(Liu et al., , 2016b and rats (Liu et al., 2020). It was taken every morning after meal. ...
... Based on the previous evidences on mice and rats, the experimental period was set for 14 days. Consecutive ingestion of PS128 for 14 days has been demonstrated to reduce anxiety-like behaviors in both germfree (Liu et al., 2016a) and naïve adult mice (Liu et al., 2016b), improve tic-like hyperactive behaviors in Tourette syndrome model rats (Liao et al., 2019), and ameliorate visceral hypersensitivity in irritable bowel syndrome model rats (Liu et al., 2020). According to these findings, we aimed to investigate effects of PS128 for 14 days on dogs with behavioral problems in this study. ...
Certain strains of Lactiplantibacillus were found to have a positive impact on host neuromodulation through the gut-brain axis and thus ameliorate emotional and behavioral problems. A number of researches have been performed on humans, mice and rats; however, studies on dogs are limited. Forty-five dogs with behavioral problems were enrolled in this study, including aggression (n=22), separation anxiety (n=15), compulsive disorder (n=7) and unclassifiable inappropriate behavior (n=1, excessive barking). The behavioral diagnosis was made based on the primary behavioral consultation questionnaires and the careful interrogations at interviews. Lactiplantibacillus plantarum PS128 (PS128) probiotic was administered to these physically healthy dogs with behavioral problems over a course of two weeks to determine the probiotic effectiveness on canine behaviors. Dogs were evaluated and scored using the Evaluation of Dog’s Emotional and cognitive Disorders (EDED) scale and the Canine Behavioral Checklist (CBC) questionnaire at the visits before and after the probiotic treatment. Plasma serotonin levels were measured using high-performance liquid chromatography- electrochemical detection (HPLC-ECD) and the serotonin turnover ratios (5-HIAA/5-HT) were compared pre- and post-treatment. The results showed that the general behavioral stability was improved, and the problems of aggression and separation anxiety were ameliorated after treatment. A significant decrease in 5-HIAA/5-HT ratio was observed in dogs with separation anxiety, suggesting a serotonin-related mechanism. These results proved that PS128 was beneficial for emotional stabilization, which might be useful as a therapeutic supplement for canine aggression and separation anxiety.
... Previously, Lactobacillus plantarum PS128 TM (PS128 TM ), isolated from spontaneously fermented mustard greens in Taiwan (21), has been demonstrated to reduce anxiety-and depressionlike behaviors (22,23), ameliorate tic-like behaviors (24), and improve visceral hypersensitivity (25) in experimental animals. Beneficial effects of PS128 TM on children with autism spectrum disorder (26), triathletes (27), and patients with major depressive disorder (28) have also been reported. ...
... Beneficial effects of PS128 TM on children with autism spectrum disorder (26), triathletes (27), and patients with major depressive disorder (28) have also been reported. PS128 TM may exert its psychotropic effects by altering monoamine neurotransmitter levels (22)(23)(24)(25), and modulating glucocorticoid (22), antiinflammatory, and anti-oxidative responses (21,22,27); however, the underlying mechanisms warrant further investigation. Despite the increase in the number of IT employees, the importance of the IT industry to the economy, and the high stress due to uncertainty and workload under time pressure, no study to date has investigated whether probiotics could help alleviate stress, sleep, or mood symptoms in highly stressed IT specialists. ...
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).
... This nervous system disorder reduces the threshold of gastrointestinal irritation, so IBS-D patients often suffer from abdominal pain and bloating [33]. In animal models, Lactobacillus species have been proven to inhibit visceral hypersensitivity by increasing the pain threshold, reducing the contractile response of colonic smooth muscle, inhibiting the concentrations of serum corticosterone and spinal neurotransmitters, and regulating the hypothalamus-pituitary-adrenal axis [35,36]. Our results are similar to these conclusions. ...
Irritable bowel syndrome with diarrhea (IBS-D) is chronic intestinal dysfunction with diarrhea and other complicated clinical symptoms, and it has a great impact on the daily life and mental state of patients. Some studies have reported that ingestion of probiotics can significantly alleviate a variety of intestinal diseases. The purpose of this study was to investigate the IBS-D-alleviating effects of a probiotic strain, Lactobacillus plantarum CCFM8610, with multiple health-promoting effects. The study was a 12-week, randomized, double-blind, placebo-controlled, pilot clinical trial. Seventy-five patients were randomly assigned to receive the placebo, oligosaccharides, or Lactobacillus plantarum CCFM8610 (1 × 10¹⁰ colony-forming units (CFU) per day), with a 2-week run-in period, an 8-week intervention period, and a 2-week follow-up observation period. The patients’ clinical symptoms and quality of life were examined by the IBS symptom severity scale (IBS-SSS) and the IBS quality of life scale (IBS-QOL). Changes in gut microbiota composition and diversity were measured at the end of the intervention period. The oral administration of L. plantarum CCFM8610 significantly decreased the IBS-SSS and IBS-QOL scores, reduced IBS-D symptom severity, recovered gut microbiota diversity, decreased the relative abundance of bloating-related genus Methanobrevibacter, and increased the relative abundance of butyric acid-producing genera, including Anaerostipes, Anaerotruncus, Bifidobacterium, Butyricimonas, and Odoribacter. These findings suggest that ingestion of L. plantarum CCFM8610 can significantly alleviate clinical symptoms and gut microbiota dysbiosis in IBS-D patients. The IBS-D-alleviating effect of L. plantarum CCFM8610 may be related to the increase in the relative abundance of butyric acid-producing genera in the intestine.
... 43 Lactobacillus plantarum PS128 ameliorated VH through gut-brain axis. 48 Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 restored intestinal permeability and gut microbiota in IBS patients. 49 Prevotella had a negative association with pain in IBS patients. ...
Background/aims:
To explore the role of intestinal flora and mast cells in visceral hypersensitivity (VH).
Methods:
The experimental animals were divided into 4 groups: control group, VH group, VH + VSL#3 group, and VH + ketotifen group. Stool samples were collected from each group (n = 3) for a further analysis using 16S ribosomal DNA gene sequence. Visceral sensitivity was evaluated by abdominal withdrawal reflex (AWR) score. Colon tissues of rats were obtained from each group. Mast cells were detected by toluidine blue staining. The degranulation of mast cells was assessed by transmission electron microscopy.
Results:
VH rat model could successfully be induced by acetic acid enema combined with partial limb restraint method. Compared with rats in the control group, AWR score, number of mast cells, and degranulation of mast cells were increased in the VH rats, which could be reduced by administration of ketotifen or probiotic VSL#3. Clostridium sensu stricto 1 abundance was higher in the VH group compared to the control group, which could be restored by application of probiotic VSL#3.
Conclusions:
Probiotic VSL#3 decreases visceral sensitivity in VH rats. The mechanism may be related to mast cell and intestinal flora. Change of Clostridium sensu stricto 1 abundance may be a basis for VH observed in irritable bowel syndrome and may be prevented by specific probiotic administration.
... Dysregulation of intestinal microbiome composition might influence BDNF release in the spinal cord and contribute to the genesis of pain. For example, a recent study demonstrated that in a rat model of visceral hypersensitivity, treatment with the probiotic Lactobacillus plantarum attenuates visceral pain responses during colorectal distension and reduces spinal BDNF expression (Liu et al., 2019). ...
Globally, it is estimated that one in five people suffer from chronic pain, with prevalence increasing with age. The pathophysiology of chronic pain encompasses complex sensory, immune, and inflammatory interactions within both the central and peripheral nervous systems. Microglia, the resident macrophages of the central nervous system (CNS), are critically involved in the initiation and persistence of chronic pain. Microglia respond to local signals from the CNS but are also modulated by signals from the gastrointestinal tract. Emerging data from preclinical and clinical studies suggest that communication between the gut microbiome, the community of bacteria residing within the gut, and microglia is involved in producing chronic pain. Targeted strategies that manipulate or restore the gut microbiome have been shown to reduce microglial activation and alleviate symptoms associated with inflammation. These data indicate that manipulations of the gut microbiome in chronic pain patients might be a viable strategy in improving pain outcomes. Herein, we discuss the evidence for a connection between microglia and the gut microbiome and explore the mechanisms by which commensal bacteria might influence microglial reactivity to drive chronic pain.
Aim:Chronic stress plays an important role in the pathophysiology of depression. In this study, we aimed to investigate the therapeutic effects of Bactolac (Lactobacillus plantarum NBIMCC 8767+Streptococcus thermophilus NBIMCC 8258) on chronic stress-induced depression in rats.
Methods:This study was performed in a total of 28 rats, in control (C), stress (S), Bactolac (B), Bactolac+stress (BS) groups (each n=7). Behavioral tests were performed to evaluate depressive behaviors (sucrose preference test, three-chamber sociability test, elevated plus maze test, forced swim test). 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NLRP3, MC4R expression levels in hippocampus tissue; NOD1 receptor expression levels in small intestine tissue were determined by RT-PCR method. BDNF levels in hippocampus tissue were determined by elisa kit. Histopathological examinations were performed in cortex and small intestine tissues.
Results:Bactolac treatment reduced depressive-like behaviors (p<0.05), NLRP3 and MC4R expression levels (p<0.05), neurodegeneration, and glial activity, increased BDNF levels. It had no effect on other parameters examined in stressed rats.
Conclusions:Chronic stress decreased the expression levels of 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1 and BDNF level; increased the expression levels of NLRP3 and MC4R, caused neurodegeneration and glial activity, ultimately led to depressive effects. Bactolac was effective in reducing depressive effects and may be a natural treatment agent for depression.
Postoperative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall and the splanchnic pain induced by the activation of nociceptors of the viscera, which are highly sensitive to distension, ischemia, and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly affected by both anesthesia and surgical manipulation. Thus, efforts to restore the disturbed microbiome via supplementation with beneficial bacteria, namely probiotics, seem to be effective. In this article, the knowledge gained mainly from experimental research on this topic is analyzed, the concluding message being that each probiotic strain works in its own way towards pain relief.
Pain perception involves current stimulation in peripheral nociceptive nerves and the subsequent stimulation of postsynaptic excitatory neurons in the spinal cord. Importantly, in chronic pain, the neural activity of both peripheral nociceptors and postsynaptic neurons in the central nervous system is influenced by several inflammatory mediators produced by the immune system. Growing evidence has indicated that the commensal microbiota plays an active role in regulating pain perception by either acting directly on nociceptors or indirectly through the modulation of the inflammatory activity on immune cells. This symbiotic relationship is mediated by soluble bacterial mediators or intrinsic structural components of bacteria that act on eukaryotic cells, including neurons, microglia, astrocytes, macrophages, T-cells, enterochromaffin cells, and enteric glial cells. The molecular mechanisms involve bacterial molecules that act directly on neurons affecting their excitability, or indirectly on non-neuronal cells inducing changes in the production of pro-inflammatory or anti-inflammatory mediators. Importantly, Parkinson's disease, a neurodegenerative and inflammatory disorder that affect mainly the dopaminergic neurons implicated in the control of voluntary movements, involves not only a motor decline but also non-motor symptomatology, including chronic pain. Of note, several recent studies have shown that Parkinson's disease involves a dysbiosis in the composition of the gut microbiota. In this review, first, we summarize, integrate and classify the molecular mechanisms implicated in the microbiota-mediated regulation of chronic pain. Secondly, we analyze the changes on the commensal microbiota associated to Parkinson's disease and propose how these changes affect the development of chronic pain in this pathology. Significance Statement The microbiota regulates chronic-pain through the action of bacterial signals into two main locations: the peripheral nociceptors and the postsynaptic excitatory neurons in the spinal cord. The dysbiosis associated to Parkinson's disease reveals increased representation of commensals that potentially exacerbate chronic pain and reduced levels of bacteria with beneficial effects on pain. This review encourages further research to better understand the signals involved in bacteria-bacteria and bacteria-host communication to get the clues for the development of probiotics with therapeutic potential.
