Sapienbiotics

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Lactobacillus plantarum

Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish

Abstract

The consumption of probiotics has become increasingly popular as a means to try to improve health and well-being. Not only are probiotics considered beneficial to digestive health, but increasing evidence suggests direct and indirect interactions between gut microbiota (GM) and the central nervous system (CNS). Here, adult zebrafish were supplemented with Lactobacillus plantarum to determine the effects of probiotic treatment on structural and functional changes of the GM, as well as host neurological and behavioral changes. L. plantarum administration altered the β-diversity of the GM while leaving the major core architecture intact. These minor structural changes were accompanied by significant enrichment of several predicted metabolic pathways. In addition to GM modifications, L. plantarum treatment also significantly reduced anxiety-related behavior and altered GABAergic and serotonergic signaling in the brain. Lastly, L. plantarum supplementation provided protection against stress-induced dysbiosis of the GM. These results underscore the influence commensal microbes have on physiological function in the host and demonstrate bidirectional communication between the GM and the host.

Source: Davis, D., Doerr, H., Grzelak, A. et al. “Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish.” Sci Rep 6, 33726 (2016).

Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomized, double-blind, placebo-controlled study

Abstract

Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomized, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×109 cfu/day) for 12 weeks reduced symptoms of stress (P=0.024), anxiety (P=0.001), and total psychological scores (P=0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 (P<0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning (P<0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo (P<0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.

Source: Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, Yusoff MSB, Wahid N, Abdullah MFIL, Zakaria N, Ong KL, Park YH, Liong MT. “Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomized, double-blind, placebo-controlled study.” Benef Microbes. (2019);10(4):355-373.

Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice

Abstract

Ingestion of specific probiotics, namely "psychobiotics", produces psychotropic effects on behavior and affects the hypothalamic-pituitary-adrenal axis and neurochemicals in the brain. We examined the psychotropic effects of a potential psychobiotic bacterium, Lactobacillus plantarum strain PS128 (PS128), on mice subjected to early life stress (ELS) and on naïve adult mice. Behavioral tests revealed that chronic ingestion of PS128 increased the locomotor activities in both ELS and naïve adult mice in the open field test. In the elevated plus maze, PS128 significantly reduced the anxiety-like behaviors in naïve adult mice but not in the ELS mice; whereas the depression-like behaviors were reduced in ELS mice but not in naïve mice in forced swimming test and sucrose preference test. PS128 administration also reduced ELS-induced elevation of serum corticosterone under both basal and stressed states but had no effect on naïve mice. In addition, PS128 reduced inflammatory cytokine levels and increased anti-inflammatory cytokine level in the serum of ELS mice. Furthermore, the dopamine level in the prefrontal cortex (PFC) was significantly increased in PS128 treated ELS and naïve adult mice whereas serotonin (5-HT) level was increased only in the naïve adult mice. These results suggest that chronic ingestion of PS128 could ameliorate anxiety- and depression-like behaviors and modulate neurochemicals related to affective disorders. Thus PS128 shows psychotropic properties and has great potential for improving stress-related symptoms.

Source: Liu YW, Liu WH, Wu CC, Juan YC, Wu YC, Tsai HP, Wang S, Tsai YC. “Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice.” Brain Res. (2016);1631:1-12.

Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice

Abstract

Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. These results suggest that the chronic administration of PS128 is safe and could induce changes in emotional behaviors. The behavioral changes are correlated with the increase in the monoamine neurotransmitters in the striatum. These findings suggest that daily intake of the L. plantarum strain PS128 could improve anxiety-like behaviors and may be helpful in ameliorating neuropsychiatric disorders.

Source: Liu WH, Chuang HL, Huang YT, Wu CC, Chou GT, Wang S, Tsai YC. “Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice.” Behav Brain Res. (2016);298(Pt B):202-9.

Lactobacillus casei

A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome

Abstract

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.

Source: Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, Logan AC. “A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome.” Gut Pathog. (2009);1(1):6.

The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers

Abstract

Objective: The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic-pituitary-adrenal axis in petrochemical workers.

Methods: The present randomized double-blind, placebo-controlled trial was conducted on 70 petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule (n = 25) or one probiotic capsule daily + 100 g/day conventional yogurt (n = 25) or 100 g/day conventional yogurt + one placebo capsule (n = 20) for 6 weeks. Mental health parameters including general health questionnaire (GHQ) and depression anxiety and stress scale (DASS) scores were measured. Fasting blood samples were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic-pituitary-adrenal axis.

Results: After 6 weeks of intervention, a significant improvement of GHQ was observed in the probiotic yogurt (18.0 ± 1.5 vs. 13.5 ± 1.9, P = 0.007) and in the probiotic capsule group (16.9 ± 1.8 vs. 9.8 ± 1.9, P = 0.001), as well as a significant improvement in DASS scores in the probiotic yogurt (23.3 ± 3.7 vs. 13.0 ± 3.7, P = 0.02) and the probiotic capsule group (18.9 ± 3.2 vs. 9.4 ± 4.0, P = 0.006). However, there was no significant improvement in the conventional yogurt group (P = 0.05 for GHQ and P = 0.08 for DASS).

Discussion: The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers.

Source: Mohammadi AA, Jazayeri S, Khosravi-Darani K, Solati Z, Mohammadpour N, Asemi Z, Adab Z, Djalali M, Tehrani-Doost M, Hosseini M, Eghtesadi S. “The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers.” Nutr Neurosci. (2016);19(9):387-395.

Lactobacillus rhamnosus

The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria

Abstract

There is accumulating evidence that certain gut microbes modulate brain chemistry and have antidepressant-like behavioural effects. However, it is unclear which brain regions respond to bacteria-derived signals or how signals are transmitted to distinct regions. We investigated the role of the vagus in mediating neuronal activation following oral treatment with Lactobacillus rhamnosus (JB-1). Male Balb/c mice were orally administered a single dose of saline or a live or heat-killed preparation of a physiologically active bacterial strain, Lactobacillus rhamnosus (JB-1). 165 min later, c-Fos immunoreactivity in the brain was mapped, and mesenteric vagal afferent fibre firing was recorded. Mice also underwent sub-diaphragmatic vagotomy to investigate whether severing the vagus prevented JB-1-induced c-Fos expression. Finally, we examined the ΔFosB response following acute versus chronic bacterial treatment. While a single exposure to live and heat-killed bacteria altered vagal activity, only live treatment induced rapid neural activation in widespread but distinct brain regions, as assessed by c-Fos expression. Sub-diaphragmatic vagotomy abolished c-Fos immunoreactivity in most, but not all, previously responsive regions. Chronic, but not acute treatment induced a distinct pattern of ΔFosB expression, including in previously unresponsive brain regions. These data identify that specific brain regions respond rapidly to gut microbes via vagal-dependent and independent pathways, and demonstrate that acute versus long-term exposure is associated with differential responses in distinct brain regions.

Source: Bharwani A, West C, Champagne-Jorgensen K, McVey Neufeld KA, Ruberto J, Kunze WA, Bienenstock J, Forsythe P. “The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria.” Neuropharmacology. (2020);170:108067.

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial

Abstract

Background: Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms.

Objective: The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12 months of age.

Design, setting, participants: A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16 weeks gestation.

Intervention: Women were randomised to receive either placebo or HN001 daily from enrolment until 6 months postpartum if breastfeeding.

Outcome measures: Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum.

Trial registration: Australia NZ Clinical Trials Registry: ACTRN12612000196842.

Findings: 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002).

Interpretation: Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum.

Source: Slykerman RF, Hood F, Wickens K, Thompson JMD, Barthow C, Murphy R, Kang J, Rowden J, Stone P, Crane J, Stanley T, Abels P, Purdie G, Maude R, Mitchell EA; Probiotic in Pregnancy Study Group. “Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.” EBioMedicine. (2017);24:159-165.

Bifidobacterium longum

Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress

Abstract

Objectives: Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum 1714™ has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714™ to modulate brain function in humans is unclear.

Methods: In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the "Cyberball game," a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 10 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey.

Results: B. longum 1714™ altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex (P < 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and temporal cortex (P < 0.05), both of which were associated with subjective vitality changes. All groups showed increased social stress after a 4-week intervention without an effect at behavioral level due to small sample numbers. However, only B. longum 1714™ altered neural oscillation after social stress, with increased theta and alpha band power in the frontal and cingulate cortex (P < 0.05) and supramarginal gyrus (P < 0.05).

Discussion: B. longum 1714™ modulated resting neural activity that correlated with enhanced vitality and reduced mental fatigue. Furthermore, B. longum 1714™ modulated neural responses during social stress, which may be involved in the activation of brain coping centers to counter-regulate negative emotions.

Source: Wang H, Braun C, Murphy EF, Enck P. “Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress.” Am J Gastroenterol. (2019);114(7):1152-1162.

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

Abstract

The emerging concept of psychobiotics—live microorganisms with a potential mental health benefit—represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

Source: Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J. F., Dinan, T. G., & Clarke, G. “Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.” Translational psychiatry (2016), 6(11), e939.

Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice

Abstract

An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.

Source: Kim H, Shin J, Kim S, Kim S, Cho B, Park SJ, Park G, Shin H, Park MS, Kim J. “Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice.” Biochem Biophys Res Commun. (2022);603:41-48.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects

Abstract

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Source: Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. “Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.” Br J Nutr. (2011);105(5):755-64.

Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers

Abstract

Methods: In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the “Cyberball game,” a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 109 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey.

Source: Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. “Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers.” Gut Microbes. (2011);2(4):256-61.

Bifidobacterium breve

Fermented foods, neuroticism, and social anxiety: An interaction model

Abstract

Animal models and clinical trials in humans suggest that probiotics can have an anxiolytic effect. However, no studies have examined the relationship between probiotics and social anxiety. Here we employ a cross-sectional approach to determine whether consumption of fermented foods likely to contain probiotics interacts with neuroticism to predict social anxiety symptoms. A sample of young adults (N=710, 445 female) completed self-report measures of fermented food consumption, neuroticism, and social anxiety. An interaction model, controlling for demographics, general consumption of healthful foods, and exercise frequency, showed that exercise frequency, neuroticism, and fermented food consumption significantly and independently predicted social anxiety. Moreover, fermented food consumption also interacted with neuroticism in predicting social anxiety. Specifically, for those high in neuroticism, higher frequency of fermented food consumption was associated with fewer symptoms of social anxiety. Taken together with previous studies, the results suggest that fermented foods that contain probiotics may have a protective effect against social anxiety symptoms for those at higher genetic risk, as indexed by trait neuroticism. While additional research is necessary to determine the direction of causality, these results suggest that consumption of fermented foods that contain probiotics may serve as a low-risk intervention for reducing social anxiety.

Source: Hilimire MR, DeVylder JE, Forestell CA. “Fermented foods, neuroticism, and social anxiety: An interaction model.” Psychiatry Res. (2015);228(2):203-8.

Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice

Abstract

Background: Accumulating evidence points to an association between gut microbial abnormalities and depression disorder. The microbiota-gut-brain axis is an emerging target for treating depression using nutritional strategies, considering the numerous limitations of current pharmacological approaches. Here we studied the effect and probable mechanisms of psychobiotic treatment on depression.

Methods: Chronically stressed C57BL/6J male mice were administered viable Bifidobacterium breve CCFM1025 for 5 weeks prior to behavioral testing. Brain neurological alterations, serum corticosterone, cytokines levels, fecal microbial composition, and short-chain fatty acid (SCFA) content were measured. In addition, the effect of SCFA on 5-hydroxytryptophan (5-HTP) biosynthesis was investigated in an in vitro model of enterochromaffin cells (RIN14B).

Results: CCFM1025 treatment significantly reduced depression- and anxiety-like behaviors. The hyperactive hypothalamic-pituitary-adrenal response, as well as inflammation, were also alleviated, possibly via regulating the expression of glucocorticoid receptors (Nr3c1). Moreover, CCFM1025 also down-regulated the pCREB-c-Fos pathway but increased the expression of brain-derived neurotrophic factor (BDNF). Meanwhile, chronic stress-induced gut microbial abnormalities were restored, accompanied by increased SCFA and 5-HTP levels. The intestinal 5-HTP biosynthesis positively correlated with fecal SCFA and Bifidobacterium breve levels.

Conclusions: In summary, Bifidobacterium breve CCFM1025 showed considerable antidepressant-like and microbiota-regulating effects, which opens avenues for novel therapeutic strategies towards treating depression.

Source: Tian, P., O'Riordan, K. J., Lee, Y. K., Wang, G., Zhao, J., Zhang, H., Cryan, J. F., & Chen, W. “Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice.” Neurobiology of stress (2020), 12, 100216.

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study

Abstract

Background: Studies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines.

Methods: In this open-label single-arm study, all participants received B. breve strain A-1 (1011 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition.

Results: Twenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders.

Limitations: This open-label, single-arm study cannot exclude a placebo effect.

Conclusions: The results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome.

Source: Okubo R, Koga M, Katsumata N, Odamaki T, Matsuyama S, Oka M, Narita H, Hashimoto N, Kusumi I, Xiao J, Matsuoka YJ. “Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study.” J Affect Disord. (2019);245:377-385.

Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice

Abstract

Background: Accumulating evidence suggests that commensal bacteria consumption has the potential to have a positive impact on stress-related psychiatric disorders. However, the specific bacteria influencing behaviors related to anxiety and depression remain unclear. To this end, we compared the effects of two different Bifidobacteria on anxiety and depression-like behavior; an antidepressant was also used as a comparator.

Methods: Innately anxious BALB/c mice received daily Bifidobacterium longum (B.) 1714, B. breve 1205, the antidepressant escitalopram or vehicle treatment for 6 weeks. Behavior was assessed in stress-induced hyperthermia test, marble burying, elevated plus maze, open field, tail suspension test, and forced swim test. Physiological responses to acute stress were also assessed.

Key results: Both Bifidobacteria and escitalopram reduced anxiety in the marble burying test; however, only B. longum 1714 decreased stress-induced hyperthermia. B. breve 1205 induced lower anxiety in the elevated plus maze whereas B. longum 1714 induced antidepressant-like behavior in the tail suspension test. However, there was no difference in corticosterone levels between groups.

Conclusions & inferences: These data show that these two Bifidobacteria strains reduced anxiety in an anxious mouse strain. These results also suggest that each bacterial strain has intrinsic effects and may be beneficially specific for a given disorder. These findings strengthen the role of gut microbiota supplementation as psychobiotic-based strategies for stress-related brain-gut axis disorders, opening new avenues in the field of neurogastroenterology.

Source: Savignac HM, Kiely B, Dinan TG, Cryan JF. “Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice.” Neurogastroenterol Motil. (2014);26(11):1615-27.

Probiotic Blend – Microbiome Diversity and Anxiety

Gut microbiome composition and diversity are related to human personality traits

Abstract

The gut microbiome has a measurable impact on the brain, influencing stress, anxiety, depressive symptoms and social behaviour. This microbiome–gut–brain axis may be mediated by various mechanisms including neural, immune and endocrine signalling. To date, the majority of research has been conducted in animal models, while the limited number of human studies has focused on psychiatric conditions. Here the composition and diversity of the gut microbiome is investigated with respect to human personality. Using regression models to control for possible confounding factors, the abundances of specific bacterial genera are shown to be significantly predicted by personality traits. Diversity analyses of the gut microbiome reveal that people with larger social networks tend to have a more diverse microbiome, suggesting that social interactions may shape the microbial community of the human gut. In contrast, anxiety and stress are linked to reduced diversity and an altered microbiome composition. Together, these results add a new dimension to our understanding of personality and reveal that the microbiome–gut–brain axis may also be relevant to behavioural variation in the general population as well as to cases of psychiatric disorders.

Source: Johnson KV. “Gut microbiome composition and diversity are related to human personality traits.” Hum Microb J. (2020);15:None.

Gut microbiota’s effect on mental health: The gut-brain axis

Abstract

The bidirectional communication between the central nervous system and gut microbiota, referred to as the gut-brain-axis, has been of significant interest in recent years. Increasing evidence has associated gut microbiota to both gastrointestinal and extragastrointestinal diseases. Dysbiosis and inflammation of the gut have been linked to causing several mental illnesses including anxiety and depression, which are prevalent in society today. Probiotics have the ability to restore normal microbial balance, and therefore have a potential role in the treatment and prevention of anxiety and depression. This review aims to discuss the development of the gut microbiota, the linkage of dysbiosis to anxiety and depression, and possible applications of probiotics to reduce symptoms.

Source: Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. “Gut microbiota's effect on mental health: The gut-brain axis.” Clin Pract. (2017);7(4):987.

Emotional well-being and gut microbiome profiles by enterotype

Abstract

With increasing attention being paid to improving emotional well-being, recent evidence points to gut microbiota as a key player in regulating mental and physical health via bidirectional communication between the brain and gut. Here, we examine the association between emotional well-being and gut microbiome profiles (i.e., gut microbiome composition, diversity, and the moderating role of the enterotypes) among healthy Korean adults (n = 83, mean age = 48.9, SD = 13.2). The research was performed using high-throughput 16S rRNA gene sequencing to obtain gut microbiome profiles, as well as a self-report survey that included the Positive Affect Negative Affect Schedule (PANAS). The cluster-based analysis identified two enterotypes dominated by the genera Bacteroides (n = 49) and Prevotella (n = 34). Generalized linear regression analysis reveals significant associations between positive emotion and gut microbiome diversity (Shannon Index) among participants in the Prevotella dominant group, whereas no such relationship emerged among participants in the Bacteroides group. Moreover, a novel genus from the family Lachnospiraceae is associated with emotional well-being scores, both positive and negative. Together, the current findings highlight the enterotype-specific links between the gut microbiota community and emotion in healthy adults and suggest the possible roles of the gut microbiome in promoting mental health.

Source: Lee, SH., Yoon, SH., Jung, Y. et al. “Emotional well-being and gut microbiome profiles by enterotype.” Sci Rep (2020) 10, 20736.

Probiotic Blend – Additional Health Benefits

Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality

Abstract

Recent demonstration that probiotics administration has positive effects on mood state in healthy populations suggests its possible role as an adjunctive therapy for depression in clinical populations and as a non-invasive strategy to prevent depressive mood state in healthy individuals. The present study extends current knowledge on the beneficial effects of probiotics on psychological well-being, as measured by changes in mood (e.g., cognitive reactivity to sad mood, depression, and anxiety), personality dimensions, and quality of sleep, which have been considered as related to mood. For this double-blind, placebo-controlled study 38 healthy volunteers assigned to an experimental or control group assumed a daily dose of a probiotic mixture (containing Lactobacillus fermentum LF16, L. rhamnosus LR06, L. plantarum LP01, and Bifidobacterium longum BL04) or placebo, respectively, for 6 weeks. Mood, personality dimensions, and sleep quality were assessed four times (before the beginning of the study, at 3 and 6 weeks, and at 3 weeks of washout). A significant improvement in mood was observed in the experimental group, with a reduction in depressive mood state, anger, and fatigue, and an improvement in sleep quality. No between-groups differences were found. These findings corroborate the positive effect of probiotics on mood state and suggest that probiotics administration may improve psychological well-being by ameliorating aspects of mood and sleep quality.

Source: Marotta A, Sarno E, Del Casale A, et al. “Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality.” Front Psychiatry. (2019);10:164.

Probiotics may help manage childhood obesity

Abstract

Probiotics may help children and adolescents with obesity lose weight when taken alongside a calorie-controlled diet, according to a new study. The study found that obese children who were put on a calorie-restricted diet and given probiotics Bifidobacterium breve BR03 and Bifidobacterium breve B632, lost more weight and had improved insulin sensitivity compared with children on a diet only.

Source: European Society of Endocrinology. "Probiotics may help manage childhood obesity." ScienceDaily. ScienceDaily, 7 September 2020.

Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: a randomized, double-blind, placebo-controlled trial

Abstract

Accumulating evidence suggests a relationship between the gut microbiota and the development of obesity, indicating the potential of probiotics as a therapeutic approach. Bifidobacterium breve B-3 has been shown to exert anti-obesity effects in high-fat diet-induced obese mice. In the present study, the anti-obesity effects of the consumption of B. breve B-3 by healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a randomized, double-blind, placebo-controlled trial (trial registration: UMIN-CTR No. 000023919; preregistered on September 2, 2016). Eighty participants were randomized to receive placebo or B. breve B-3 capsules (2 × 1010 CFU/day) daily for 12 weeks. The visceral fat area significantly increased at weeks 4 and 8 in the placebo group only; no significant change was observed in the B-3 group. Body fat mass and percent body fat were significantly lower in the B-3 group than in the placebo group at weeks 8 and 12 (p<0.05, ANCOVA adjusted with baseline values). Although no significant differences were observed in blood parameters between the groups, the intake of B. breve B-3 slightly decreased triglyceride levels and improved HDL cholesterol from the baseline. No serious adverse effects were noted in either group. These results suggest that the probiotic strain B. breve B-3 has potential as a functional food ingredient to reduce body fat in healthy pre-obese individuals.

Source: Minami J, Iwabuchi N, Tanaka M, et al. “Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: a randomized, double-blind, placebo-controlled trial.” Biosci Microbiota Food Health. (2018);37(3):67-75.

A patented strain of Bacillus coagulans increased immune response to viral challenge

Abstract

Background: Viral respiratory tract infection is the most common illness among humans. Probiotics have been known to enhance the immune system and, therefore, may represent a significant therapeutic advancement for treating viral respiratory tract infections.

Objective: A controlled study was conducted to evaluate the effects of the patented GanedenBC30 probiotic (Bacillus coagulans GBI-30, 6086, marketed as Sustenex [Ganeden Biotech, Inc., Mayfield Heights, OH]) on the immune system when exposed to adenovirus and influenza in otherwise healthy adults.

Methods: Ten healthy men and women (average age, 44 years) were instructed to consume 1 capsule of GanedenBC30 with water once a day for 30 days. At baseline and after completion of the 30-day treatment, blood levels of cytokines were measured in vitro after T-cell exposure to adenovirus and influenza A. Each participant served as his/her own control with baseline blood draw.

Results: The use of GanedenBC30 significantly increased T-cell production of TNF-alpha in response to adenovirus exposure (P = 0.027) and influenza A (H3N2 Texas strain) exposure (P = 0.004), but it did not have a significant effect on the response to other strains of influenza. No serious adverse events were reported throughout the study.

Conclusions: The patented GanedenBC30 probiotic may be a safe and effective therapeutic option for enhancing T-cell response to certain viral respiratory tract infections.

Source: Baron M. “A patented strain of Bacillus coagulans increased immune response to viral challenge.” Postgrad Med. (2009);121(2):114-8.

Effect of probiotic and prebiotic fermented milk on skin and intestinal conditions in healthy young female students

Abstract

Although persistent constipation is considered to be associated with skin problems, the supporting evidence is limited. Hence, this study investigated the effects of probiotic and prebiotic fermented milk on skin and intestinal conditions in an open-label trial. Among the 101 Japanese healthy young female students that participated, the 81 subjects in the intake group consumed a bottle of probiotic and prebiotic fermented milk containing Bifidobacterium breve strain Yakult and galactooligosaccharides daily for 4 weeks after a pre-intake period of 4 weeks, while the 20 subjects in the non-intake group did not consume the test beverage. Defecation patterns, skin conditions including hydration levels in the stratum corneum, and urinary phenol and p-cresol levels were evaluated before (baseline) and after intake. All subjects completed the study. No differences in dietary intake and body mass index were observed between both groups during the trial. In the intake group, hydration levels of the stratum corneum, defecation frequency, and feces quantity significantly increased, and urinary phenol and p-cresol levels significantly decreased after intake compared with the corresponding baseline values. However, they did not significantly change in the non-intake group. A significant difference was observed between the intake group and non-intake group in regard to clearness of the skin as assessed by visual analogue scale. Therefore, consecutive intake of probiotic and prebiotic fermented milk might have beneficial effects on the skin that prevent dryness and beneficial effects on the intestinal conditions that stimulate defecation and decrease phenol production by gut bacteria in healthy young women.

Source: Mori N, Kano M, Masuoka N, et al. “Effect of probiotic and prebiotic fermented milk on skin and intestinal conditions in healthy young female students.” Biosci Microbiota Food Health. (2016);35(3):105-112.

Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy

Abstract

Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 108–109 colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.

Source: Parvaneh, K., Ebrahimi, M., Sabran, M. R., Karimi, G., Hwei, A. N., Abdul-Majeed, S., Ahmad, Z., Ibrahim, Z., & Jamaluddin, R. “Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy.” BioMed research international (2015), 897639.

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

Abstract

Source: Allen, A., Hutch, W., Borre, Y. et al. “Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.” Transl Psychiatry 6, e939 (2016).

Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials

Abstract

Previous clinical studies have reported mixed results regarding the effect of probiotics on lipid metabolism. Therefore, we conducted a meta-analysis of randomized controlled trials to quantify the direction and magnitude of the potential effect of probiotics on blood lipid concentrations.Eligible studies were randomized, placebo-controlled trials whose interventions were probiotic products containing live bacteria. The studies reported net changes in lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) and their associated standard deviations (or the data to calculate them). The probiotic products did not contain prebiotics or other active ingredients, and the full article was accessible in English.The pooled mean net change in lipid profiles and 95% confidence intervals (95% CIs) were calculated. Q statistics and I were calculated to examine heterogeneity. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, and publication biases were estimated.A total of 30 randomized controlled trials with 1624 participants (828 in intervention groups and 796 in placebo groups) were included in this analysis. Subjects treated with probiotics demonstrated reduced total cholesterol and LDL cholesterol compared to control subjects by 7.8 mg/dL (95% CI: -10.4, -5.2) and 7.3 mg/dL (95% CI: -10.1, -4.4), respectively. There was no significant effect of probiotics on HDL cholesterol or triglycerides. The effect of probiotics on total cholesterol and LDL cholesterol depended on a variety of factors. The significant effects were greater for higher baseline total cholesterol levels, longer treatment durations, and certain probiotic strains. In addition, these associations seem stronger in studies supported by probiotics companies.The studies included in this meta-analysis showed significant heterogeneity as indicated by the Q statistics and I. In addition, industry sponsorship may affect study findings.These results suggest that the use of probiotics may improve lipid metabolism by decreasing total and LDL cholesterol concentrations. However, both the efficacy of probiotics for cholesterol lowering and safety should be investigated further in well-designed clinical trials.

Source: Cho YA, Kim J. “Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials.” Medicine (Baltimore). (2015);94(43):e1714.

Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production

Abstract

Recently, a probiotic Lactobacillus rhamnosus GG (LGG) has shown several beneficial effects, including improved insulin sensitivity. To clarify the mechanism underlying the insulin-sensitizing effect of LGG, mice were orally administrated with LGG for 13 weeks, and their body weight, insulin sensitivity, and expression of genes related to glucose and lipid metabolism were examined. LGG-treated mice showed attenuated weight gain and enhanced insulin sensitivity in high fat diet group, while no change was observed in normal diet-fed group. The expression of fatty acid oxidative genes in the liver was increased and gluconeogenic genes were decreased. GLUT4 mRNA expression in skeletal muscle and adiponectin production in adipose tissue were significantly increased. This was corroborated with the increased activation of AMPK in skeletal muscle and adipose tissue. Taken together, these results indicate that LGG treatment improves insulin sensitivity and reduces lipid accumulation by stimulating adiponectin secretion and consequent activation of AMPK.

Source: Kim SW, Park KY, Kim B, Kim E, Hyun CK. “Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production.” Biochem Biophys Res Commun. (2013);431(2):258-63.

Sapienbiotics

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Lactobacillus plantarum

Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish

Abstract

Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomized, double-blind, placebo-controlled study

Abstract

Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice

Abstract

Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice

Abstract

Lactobacillus casei

A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome

Abstract

The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers

Abstract

Lactobacillus rhamnosus

The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria

Abstract

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial

Abstract

Bifidobacterium longum

Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress

Abstract

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

Abstract

Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice

Abstract

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects

Abstract

Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers

Abstract

Bifidobacterium breve

Fermented foods, neuroticism, and social anxiety: An interaction model

Abstract

Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice

Abstract

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study

Abstract

Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice

Abstract

Probiotic Blend – Microbiome Diversity and Anxiety

Gut microbiome composition and diversity are related to human personality traits

Abstract

Gut microbiota’s effect on mental health: The gut-brain axis

Abstract

Emotional well-being and gut microbiome profiles by enterotype

Abstract

Probiotic Blend – Additional Health Benefits

Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality

Abstract

Probiotics may help manage childhood obesity

Abstract

Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: a randomized, double-blind, placebo-controlled trial

Abstract

A patented strain of Bacillus coagulans increased immune response to viral challenge

Abstract

Effect of probiotic and prebiotic fermented milk on skin and intestinal conditions in healthy young female students

Abstract

Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy

Abstract

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

Abstract

Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials

Abstract

Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production

Abstract

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