Bifidobacterium Longum R0175 Research Articles

The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol

BackgroundCurrent treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut–brain–microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study—a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet — is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients.MethodsA total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters.DiscussionMicrobiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits.Trial registrationNCT03877393.

Effect of Coordinated Probiotic/Prebiotic/Phytobiotic Supplementation on Microbiome Balance and Psychological Mood State in Healthy Stressed Adults

Background: Interest in and knowledge of the gut microbiome has increased exponentially in the past decade. This once overlooked component of the gastrointestinal tract is now implicated in multiple aspects of human health, including mental (e.g. depression, anxiety, stress), metabolic (e.g. diabetes/obesity), neurological (e.g. Alzheimer’s, Parkinson’s, Autism Spectrum Disorder), gastrointestinal (e.g. irritable bowel syndrome, Crohn’s), and immunological (e.g. inflammation, cancer) wellness, among others. Previous research has demonstrated the “strain specificity” of probiotic therapy (e.g. Lactobacillus helveticus R0052 for serotonin/depression; Bifidobacterium longum R0175 for GABA/anxiety; Lactobacillus rhamnosus R0011 for cortisol/stress). Similarly, probiotic bacteria demonstrate different growth trajectories based on availability of preferred fiber substrates (e.g. prebiotics) and phytonutrients such as flavonoids/polyphenols (e.g. phytobiotics). Thus, our objective was two-fold: to determine the change in microbiome ecology/balance and to evaluate the psychological mood state following a coordinated pro-/pre-/phyto-biotic supplementation regimen.Methods: Thirty-two healthy subjects screened for “moderate” levels of psychological stress were randomly assigned to 1-month of Supplement (Amare Fundamentals, N=21) or matching Placebo (N=11). Microbiome balance was assessed in fecal samples using a PCR-based analysis (BiomeTracker) that has previously compared favorably to 16S sequencing for abundance quantification for major phyla/families of bacteria. Psychological mood state parameters were assessed using the validated Profile of Mood States survey (POMS) to generate scores for Global Mood State, and six sub-scales (Depression, Tension, Fatigue, Anger, Confusion, and Vigor).Results: Following supplementation, there was a significant increase in populations of “good” bacteria in the Supplement group (+28% Lactobacillus; +30% Bifidobacterium) and overall composite score (+17%) versus Placebo (p<0.05). Psychological indices were significantly improved in the Supplement group for both positive (+25% Global Mood; +44% Vigor) and negative (-64% Fatigue; -55% Depression; -54% Anger; -45% Tension; -43% Confusion) mood state parameters versus Placebo (p<0.05).Conclusion: The World Health Organization has identified mental wellness issues as the leading contributor to global health burden – highlighting the urgency to develop lifestyle interventions to effectively manage depression, anxiety, and stress. These results demonstrate the close relationship between microbiome balance and psychological parameters – and the utility of targeted supplementation to positively influence the gut-brain-axis for improved mental wellness.Keywords: Lactobacillus helveticus, Bifidobacterium longum, Lactobacillus rhamnosus, depression, anxiety, stress, vigor, mood state, mental wellness

Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats.

In recent years, the beneficial impact of targeted gut microbiota manipulation in various neurological disorders has become more evident. Therefore, probiotics have been considered as a promising approach to modulate brain gene expression and neuronal pathways even in some neurodegenerative diseases. The purpose of this study was to determine the effect of probiotic biotherapy with combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the expression levels of proteins critical to neuronal apoptosis in hippocampus of lipopolysaccharide (LPS)-exposed rats. Four groups of animals (Control, LPS, Probiotic + LPS, and Probiotic) were treated with maltodextrin (placebo) or probiotic (109CFU/ml/rat) for 2weeks by gavage. On the 15th day, a single intraperitoneal dose of saline or LPS (1mg/kg) was injected and 4h later, protein assessment was performed by western blotting in hippocampal tissues. LPS significantly increased the Bax, Bax/Bcl-2 ratio, and cleaved caspase-3 expression along with decreased the Bcl-2 and procaspase-3 protein levels. However, probiotic pretreatment (L. helveticus R0052 + B. longum R0175) significantly downregulated the Bax and Bax/Bcl-2 ratio accompanied with upregulated Bcl-2 expression. Prophylactic treatment with these bacteria also attenuated LPS-induced caspase-3 activation by remarkably increasing the expression of procaspase-3 while reducing the level of cleaved caspase-3 in target tissues. Our data indicate that probiotic formulation (L. helveticus R0052 + B. longum R0175) alleviated hippocampal apoptosis induced by LPS in rats via the gut-brain axis and suggest that this probiotic could play a beneficial role in some neurodegenerative conditions.

Oral Probiotics Ameliorate the Behavioral Deficits Induced by Chronic Mild Stress in Mice via the Gut Microbiota-Inflammation Axis

In recent years, a burgeoning body of research has revealed links between depression and the gut microbiota, leading to the therapeutic use of probiotics for stress-related disorders. In this study, we explored the potential antidepressant efficacy of a multi-strain probiotics treatment (Lactobacillus helveticus R0052, Lactobacillus plantarum R1012, and Bifidobacterium longum R0175) in a chronic mild stress (CMS) mouse model of depression and determined its probable mechanism of action. Our findings revealed that mice subjected to CMS exhibited anxiety- and depressive-like behaviors in the sucrose preference test, elevated plus maze, and forced swim test, along with increased interferon-γ, tumor necrosis factor-α, and indoleamine 2,3-dioxygenase-1 levels in the hippocampus. Moreover, the microbiota distinctly changed from the non-stress group and was characterized by highly diverse bacterial communities associated with significant reductions in Lactobacillus species. Probiotics attenuated CMS-induced anxiety- and depressive-like behaviors, significantly increased Lactobacillus abundance, and reversed the CMS-induced immune changes in the hippocampus. Thus, the possible mechanism involved in the antidepressant-like activity of probiotics is correlated with Lactobacillus species via the gut microbiota-inflammation-brain axis.

The Effects of Probiotic Formulation Pretreatment (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on a Lipopolysaccharide Rat Model

Objective: The role of gut microbiota in the pathogenesis of several neurodegenerative disorders, including Alzheimer’s disease (AD), via the gut–brain axis has recently been demonstrated; hence, modification of the intestinal microbiota composition by probiotic biotherapy could be a therapeutic target for these conditions. The aim of this study was to assess the effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on inflammatory and memory processes in lipopolysaccharide (LPS)-induced rats, one of the animal models used in peripherally induced neuroinflammation and neurodegeneration.Methods: Rats were randomly divided into four groups (Control, LPS, Probiotic + LPS, and Probiotic). All experimental groups were orally administrated maltodextrin (placebo) or probiotic (109 CFU/ml/rat) for 14 consecutive days and then were injected with saline or LPS (1 mg/kg, intraperitoneally [i.p.], single dose) 20 hours later. Memory retention ability and systemic and neuroinflammatory markers were assessed 4 hours after the injections.Results: Systemic exposure to LPS resulted in significant elevation of both the circulating and hippocampal levels of proinflammatory cytokines, which decreased remarkably following probiotic pretreatment. Oral bacteriotherapy with a combination of L. helveticus R0052 and B. longum R0175 also attenuated the decremental effect of LPS on memory through brain-derived neurotrophic factor (BDNF) expression at the molecular level; however, this effect was not significant in the passive avoidance test at the behavioral level.Conclusions: These results suggest that the management of gut microbiota with this probiotic formulation could be a promising intervention to improve neuroinflammation-associated disorders such as AD.

Effect of Coordinated Probiotic/Prebiotic/Phytobiotic Supplementation on Microbiome Balance and Psychological Mood State in Healthy Stressed Adults

BackgroundInterest in and knowledge of the gut microbiome has increased exponentially in the past decade. This once overlooked component of the gastrointestinal tract is now implicated in multiple aspects of human health, including mental wellness (e.g. depression, anxiety, stress), metabolic (e.g. diabetes, obesity), neurologic (e.g. Alzheimer's, Parkinson's, Autism Spectrum Disorder), gastrointestinal (e.g. irritable bowel syndrome, Crohn's), and immunologic (e.g. inflammation, cancer), among others.Purpose/ObjectivesPrevious research has demonstrated the “strain specificity” of probiotic therapy – elucidating that targeted health benefits are related to the specific strain of bacteria (e.g. Lactobacillus helveticus R0052 for serotonin/depression; Bifidobacterium longum R0175 for GABA/anxiety; Lactobacillus rhamnosus R0011 for cortisol/stress). Similarly, probiotic bacteria demonstrate different growth trajectories based on availability of preferred fiber substrates (e.g. prebiotics) and phytonutrients such as flavonoids/polyphenols (e.g. phytobiotics). Thus, our objective was two‐fold: to determine the change in microbiome ecology/balance; and to assess the change in psychological mood state (e.g. depression/anxiety/vigor) following a coordinated pro‐/pre‐/phyto‐biotic supplementation regimen.MethodsThirty‐two healthy subjects screened for “moderate” levels of psychological stress were randomly assigned to 30‐days of Supplement (Amare Fundamentals containing specific strains of probiotic bacteria, prebiotic fibers, and phytobiotic plant extracts, N=21) or look‐alike Placebo (N=11). Microbiome balance was assessed in fecal samples using a PCR‐based analysis (BiomeTracker) that has previously compared favorably to 16S sequencing (ACN 2017) for abundance quantification for major phyla/families of bacteria. Psychological mood state parameters were assessed using the validated Profile of Mood States survey (POMS) to generate scores for Global Mood State, and six sub‐scales (Depression, Tension, Fatigue, Anger, Confusion, and Vigor).ResultsFollowing 30‐days of supplementation, there was a significant increase in populations of “good” bacteria in the Supplement group (+28% Lactobacillus; +30% Bifidobacterium) and overall composite score (+17%) versus Placebo (p<0.05). Psychological indices were significantly improved in the Supplement group for both positive (+25% Global Mood; +25% Vigor) and negative (−60% Depression; −54% Tension; −52% Fatigue; −42% Confusion; −39% Anger) parameters versus Placebo (p<0.05).ConclusionsThe World Health Organization has identified mental wellness issues as the leading contributor to global health burden – highlighting the urgency to develop lifestyle interventions to effectively manage depression, anxiety, and stress. These results demonstrate the close relationship between microbiome balance and psychological parameters – and the utility of targeted supplementation to positively influence the gut‐brain‐axis for improved mental wellness.Support or Funding InformationThis trial was funded by Amare Global and conducted jointly by EQQIL and Wasatch ScientificThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Coordinated Probiotic/Prebiotic/Phytobiotic Supplementation on Microbiome Balance and Psychological Mood State in Healthy Stressed Adults

BackgroundInterest in and knowledge of the gut microbiome has increased exponentially in the past decade. This once overlooked component of the gastrointestinal tract is now implicated in multiple aspects of human health, including mental wellness (e.g. depression, anxiety, stress), metabolic (e.g. diabetes, obesity), neurologic (e.g. Alzheimer's, Parkinson's, Autism Spectrum Disorder), gastrointestinal (e.g. irritable bowel syndrome, Crohn's), and immunologic (e.g. inflammation, cancer), among others.Purpose/ObjectivesPrevious research has demonstrated the “strain specificity” of probiotic therapy – elucidating that targeted health benefits are related to the specific strain of bacteria (e.g. Lactobacillus helveticus R0052 for serotonin/depression; Bifidobacterium longum R0175 for GABA/anxiety; Lactobacillus rhamnosus R0011 for cortisol/stress). Similarly, probiotic bacteria demonstrate different growth trajectories based on availability of preferred fiber substrates (e.g. prebiotics) and phytonutrients such as flavonoids/polyphenols (e.g. phytobiotics). Thus, our objective was two‐fold: to determine the change in microbiome ecology/balance; and to assess the change in psychological mood state (e.g. depression/anxiety/vigor) following a coordinated pro‐/pre‐/phyto‐biotic supplementation regimen.MethodsThirty‐two healthy subjects screened for “moderate” levels of psychological stress were randomly assigned to 30‐days of Supplement (Amare Fundamentals containing specific strains of probiotic bacteria, prebiotic fibers, and phytobiotic plant extracts, N=21) or look‐alike Placebo (N=11). Microbiome balance was assessed in fecal samples using a PCR‐based analysis (BiomeTracker) that has previously compared favorably to 16S sequencing (ACN 2017) for abundance quantification for major phyla/families of bacteria. Psychological mood state parameters were assessed using the validated Profile of Mood States survey (POMS) to generate scores for Global Mood State, and six sub‐scales (Depression, Tension, Fatigue, Anger, Confusion, and Vigor).ResultsFollowing 30‐days of supplementation, there was a significant increase in populations of “good” bacteria in the Supplement group (+28% Lactobacillus; +30% Bifidobacterium) and overall composite score (+17%) versus Placebo (p<0.05). Psychological indices were significantly improved in the Supplement group for both positive (+25% Global Mood; +25% Vigor) and negative (−60% Depression; −54% Tension; −52% Fatigue; −42% Confusion; −39% Anger) parameters versus Placebo (p<0.05).ConclusionsThe World Health Organization has identified mental wellness issues as the leading contributor to global health burden – highlighting the urgency to develop lifestyle interventions to effectively manage depression, anxiety, and stress. These results demonstrate the close relationship between microbiome balance and psychological parameters – and the utility of targeted supplementation to positively influence the gut‐brain‐axis for improved mental wellness.Support or Funding InformationThis trial was funded by Amare Global and conducted jointly by EQQIL and Wasatch ScientificThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation

Background/AimsVisceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis.MethodsAfter a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured.ResultsA pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic.ConclusionThe combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.

Catabolism of citrus flavanones by the probiotics Bifidobacterium longum and Lactobacillus rhamnosus.

Orange juice (OJ) flavanones undergo limited absorption in the upper gastrointestinal tract and reach the colon where they are transformed by the microbiota prior to absorption. This study investigated the ability of two probiotic bacteria, Bifidobacterium longum R0175 and Lactobacillus rhamnosus subsp. Rhamnosus NCTC 10302 to catabolise OJ flavanones. The bacteria were incubated with hesperetin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperetin and naringenin, and the culture medium and intracellular cell extracts were collected at intervals over a 48h of incubation period. The flavanones and their phenolic acid catabolites were identified and quantified by HPLC-HR-MS. Both probiotics were able to subject hesperetin to ring fission yielding 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid which was subsequently demethylated producing 3-(3',4'-dihydroxyphenyl)propionic acid and then via successive dehydroxylations converted to 3-(3'-hydroxyphenyl)propionic acid and 3-(phenyl)propionic acid. Incubation of both bacteria with naringenin resulted in its conversion to 3-(4'-hydroxyphenyl)propionic acid which underwent dehydroxylation yielding 3-(phenyl)propionic acid. In addition, only L. rhamnosus exhibited rhamnosidase and glucosidase activity and unlike B. longum, which was able to convert hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside to their respective aglycones. The aglycones were then subjected to ring fission and further catabolised in a similar manner to that described above. The flavanones and their catabolites were found in the culture medium but not accumulated in the bacterial cells. These findings demonstrate the enzymatic potential of single strains of bifidobacterium and lactobacillus which may be involved in the colonic catabolism of OJ flavanones in vivo.

Modulation of the TNFα-induced gene expression profile of intestinal epithelial cells by soy fermented with lactic acid bacteria

The effect of soy ferments on gene expression induced by the proinflammatory cytokine tumour necrosis factor α (TNFα) at the intestinal epithelial cell (IEC) level was evaluated. Microarray-based transcriptional analysis revealed that soy fermented with Lactobacillus helveticus R0052 and Streptococcus thermophilus R0083 (SF-Lh) down-regulated 33 of 40 proinflammatory genes up-regulated by TNFα in HT-29 IEC, attenuating expression of genes encoding several proinflammatory cytokines and cell adhesion molecules. TNFα-mediated activation of gene expression associated with the NF-κB pathway was also repressed, as was Interleukin-8 (IL-8) production. In contrast, soy fermented with Bifidobacterium longum R0175 and S. thermophilus R0083 (SF-Bl) up-regulated expression of three proinflammatory genes induced by TNFα. Increased intracellular levels of hydrogen peroxide (H2O2) were detected in HT-29 IEC following incubation with SF-Lh. These results indicate that SF-Lh has immunomodulatory activity through reduction of proinflammatory gene expression at the IEC level.

Effects of storage conditions, microencapsulation and inclusion in chocolate particles on the stability of probiotic bacteria in ice cream

Three technological approaches to enhance viable counts of probiotic bacteria in ice cream were examined: post-freezing inoculation, use of a microencapsulated culture (spray-coating technology) and inclusion of cultures in chocolate or tablet particles. When a free-cell powder (FCP) of Bifidobacterium longum R0175 was added to the soft ice cream before hardening, a drop of almost 3 log cfu g−1 occurred during production and storage, while it was of only 0.43 log cfu g−1 for Lactobacillus rhamnosus R0011. However, inoculation with a powder of microencapsulated cells (MEP) improved stability of B. longum. The viability of probiotics was further improved when the MEP was incorporated into chocolate particles, which were subsequently blended into the ice cream. Viability losses of the FCP culture during storage at −16 °C in a household freezer having periodic defrost cycles were 10 times higher than when constantly maintained at −20 °C.

Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans

Orange juice (OJ) flavanones are bioactive polyphenols that are absorbed principally in the large intestine. Ingestion of probiotics has been associated with favorable changes in the colonic microflora. The present study examined the acute and chronic effects of orally administered Bifidobacterium longum R0175 on the colonic microflora and bioavailability of OJ flavanones in healthy volunteers. In an acute study volunteers drank OJ with and without the microencapsulated probiotic, whereas the chronic effects were examined when OJ was consumed after daily supplementation with the probiotic over 4 weeks. Bioavailability, assessed by 0–24h urinary excretion, was similar when OJ was consumed with and without acute probiotic intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3′-O-sulfate were the main urinary flavanone metabolites. The overall urinary excretion of these metabolites after OJ ingestion and acute probiotic intake corresponded to 22% of intake, whereas excretion of key colon-derived phenolic and aromatic acids was equivalent to 21% of the ingested OJ (poly)phenols. Acute OJ consumption after chronic probiotic intake over 4 weeks resulted in the excretion of 27% of flavanone intake, and excretion of selected phenolic acids also increased significantly to 43% of (poly)phenol intake, corresponding to an overall bioavailability of 70%. Neither the probiotic bacterial profiles of stools nor the stool moisture, weight, pH, or levels of short-chain fatty acids and phenols differed significantly between treatments. These findings highlight the positive effect of chronic, but not acute, intake of microencapsulated B. longum R0175 on the bioavailability of OJ flavanones.

Membrane fatty acid composition and fluidity are involved in the resistance to freezing of Lactobacillus buchneri R1102 and Bifidobacterium longum R0175.

Determinations of membrane fatty acid composition and fluidity were used together with acidification activity and viability measurements to characterize the physiological state after freezing of Lactobacillus buchneri R1102 and Bifidobacterium longum R0175 cells harvested in the exponential and stationary growth phases. For both strains, lower membrane fluidity was achieved in cells harvested in the stationary growth phase. This change was linked to a lower unsaturated-to-saturated fatty acid ratio for both strains and a higher cyclic-to-saturated fatty acid ratio for L. buchneri R1102 alone. These membrane properties were linked to survival and to maintenance of acidification activity of the cells after freezing, which differed according to the strain and the growth phase. Survival of B. longum R0175 was increased by 10% in cells with low membrane fluidity and high relative saturated fatty acid contents, without any change in acidification activity. Acidification activity was more degraded (70 min) in L. buchneri R1102 cells displaying low membrane fluidity and high saturated and cyclic fatty acid levels. Finally, this study showed that membrane modifications induced by the growth phase differed among bacterial strains in terms of composition. By lowering membrane fluidity, these modifications could be beneficial for survival of B. longum R0175 during the freezing process but detrimental for maintenance of acidification activity of L. buchneri R1102.

Probiotic gut effect prevents the chronic psychological stress‐induced brain activity abnormality in mice

A probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 combination, Probio'Stick(®) ) displays anxiolytic-like activity and reduces apoptosis in the lymbic system in animal models of depression. Based on the hypothesis that modulation of gut microbiota by this probiotic formulation has beneficial effects on brain activity in stress conditions, we report a set of probiotic-evoked physiological, cellular, and molecular events in the brain of Probio'Stick(®) pretreated mice submitted to chronic psychological stress. Water avoidance stress (WAS) was applied or not (sham). Hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) responses to the chronic stress were assessed through plasma corticosterone and catecholamine measurements. Specific markers for neuronal activity, neurogenesis, and synaptic plasticity were used to assess brain activity. In addition, gut permeability and tight junction (TJ) proteins levels were also determinated. We observed that a pretreatment with the probiotic formulation attenuated HPA axis and ANS activities in response to WAS, and reduced cFos expression in different brain areas but Lactobacillus salivarius (a negative control) treatment was ineffective on these parameters. Moreover, probiotic pretreatment prevented the WAS-induced decrease hippocampal neurogenesis and expression changes in hypothalamic genes involved in synaptic plasticity. These central effects were associated with restoration of TJ barrier integrity in stressed mice. These data suggest that chronic stress-induced abnormal brain plasticity and reduction in neurogenesis can be prevented by a pretreatment with the Probio'Stick(®) formulation, suggesting that probiotics modulate neuroregulatory factors and various signaling pathways in the central nervous system involved in stress response.

Scientific Opinion on the substantiation of a health claim related to “Transitech®” and “improves transit and durably regulates it” pursuant to Article 13(5) of Regulation (EC) No 1924/2006

Following an application from Vivatech submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to “Transitech®” and “improves transit and durably regulates it”. The food that is the subject of the health claim is “Transitech®”, a food supplement which contains dried parts of Rheum palmatum L. and/or Rheum officinale Baillon and/or their hybrids standardised for hydroxyanthracene derivatives, of Althaea officinalis L., of Rosa centifolia L., of Ocimum basilicum L., of Coriandrum sativum L., dried juice of Cynara scolymus L. standardised for cynarine, Saccharomyces cerevisiae subsp. cerevisiae UVAFERM SC, Bifidobacterium longum R0175 and Lactobacillus helveticus R0052. The information provided was insufficient to establish that Saccharomyces cerevisiae subsp. cerevisiae UVAFERM SC was sufficiently characterised. The Panel considers that if in a combination of several microorganisms and/or ingredients one microorganism or ingredient used in the combination is not sufficiently characterised, then the combination is considered to be not sufficiently characterised. The food, “Transitech®”, which is the subject of the claim, is not sufficiently characterised. The Panel concludes that a cause and effect relationship cannot be established between the consumption of “Transitech®” and “improves transit and durably regulates it”.

The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract

Commercial literature on various probiotic products suggests that they can be taken before meals, during meals or after meals or even without meals. This has led to serious confusion for the industry and the consumer. The objective of our study was to examine the impact of the time of administration with respect to mealtime and the impact of the buffering capacity of the food on the survival of probiotic microbes during gastrointestinal transit. We used an in vitro Digestive System (IViDiS) model of the upper gastrointestinal tract to examine the survival of a commercial multi-strain probiotic, ProtecFlor®. This product, in a capsule form, contains four different microbes: two lactobacilli (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011), Bifidobacterium longum R0175 and Saccharomyces cerevisiae boulardii. Enumeration during and after transit of the stomach and duodenal models showed that survival of all the bacteria in the product was best when given with a meal or 30 minutes before a meal (cooked oatmeal with milk). Probiotics given 30 minutes after the meal did not survive in high numbers. Survival in milk with 1% milk fat and oatmeal-milk gruel were significantly better than apple juice or spring water. S. boulardii was not affected by time of meal or the buffering capacity of the meal. The protein content of the meal was probably not as important for the survival of the bacteria as the fat content. We conclude that ideally, non-enteric coated bacterial probiotic products should be taken with or just prior to a meal containing some fats.

Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model

Myocardial infarction (MI) in rats is accompanied by apoptosis in the limbic system and a behavioural syndrome similar to models of depression. We have already shown that probiotics can reduce post-MI apoptosis and designed the present study to determine if probiotics can also prevent post-MI depressive behaviour. We also tested the hypothesis that probiotics achieve their central effects through changes in the intestinal barrier. MI was induced in anaesthetised rats via 40-min transient occlusion of the left anterior coronary artery. Sham rats underwent the same surgical procedure without actual coronary occlusion. For 7 d before MI and between the seventh post-MI day and euthanasia, half the MI and sham rats were given one billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 per d dissolved in water, while the remaining animals received only the vehicle (maltodextrin). Depressive behaviour was evaluated 2 weeks post-MI in social interaction, forced swimming and passive avoidance step-down tests. Intestinal permeability was evaluated by oral administration with fluorescein isothiocyanate-dextran, 4 h before euthanasia. MI rats displayed less social interaction and impaired performance in the forced swimming and passive avoidance step-down tests compared to the sham controls (P < 0·05). Probiotics reversed the behavioural effects of MI (P < 0·05), but did not alter the behaviour of sham rats. Intestinal permeability was increased in MI rats and reversed by probiotics. In conclusion, L. helveticus R0052 and B. longum R0175 combination interferes with the development of post-MI depressive behaviour and restores intestinal barrier integrity in MI rats.

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

In a recent clinical study, we demonstrated in the general population that Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) taken in combination for 30 days decreased the global scores of hospital anxiety and depression scale (HADs), and the global severity index of the Hopkins symptoms checklist (HSCL-90), due to the decrease of the sub-scores of somatization, depression and anger-hostility spheres. Therefore, oral intake of PF showed beneficial effects on anxiety and depression related behaviors in human volunteers. From there, it is interesting to focus on the role of this probiotic formulation in the subjects with the lowest urinary free cortisol levels at baseline.This addendum presents a secondary analyse of the effects of PF in a sub-population of 25 subjects with urinary free cortisol (UFC) levels less than 50 ng/ml at baseline, on psychological distress based on the percentage of change of the perceived stress scale (PSs), the HADs and the HSCL-90 scores between baseline and follow-up. The data show that PF improves the same scores as in the general population (the HADs global score, the global severity index of the HSCL-90 and three of its sub-scores, i.e. somatization, depression and anger-hostility), as well as the PSs score and three other sub-scores of the HSCL-90, i.e. "obsessive compulsive", "anxiety", and "paranoid-ideation". Moreover, in the HSCL-90, the score of the Factor 1, related to anxiety and depression, is significantly improved over time in PF-treated subjects compared with controls.Additional preclinical data showed that PF formulation does not induce side effects such as addiction or learning and memory impairments, and therefore displays a good safety profile.Complementary hypothetical mechanisms of action are proposed to explain the functioning of the brain-gut axis, particularly the relationship between probiotics and stress-related psychopathologies, such as anxiety and depression.

Immunomodulatory bioactivity of soy and milk ferments on monocyte and macrophage models

Fermented products provide a functional food-based approach for probiotic delivery, containing both the bacteria and their potentially bioactive metabolites. This study investigated potential immunomodulatory effects of soy and dairy ferments prepared with Bifidobacterium longum R0175 or Lactobacillus helveticus R0052 in combination with Streptococcus thermophilus ST5 on a human monocyte model (U937). We examined the effects of both soy and dairy ferments on TGF-β1 production by U937 cells challenged with the pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) at either the monocyte stage or the macrophage stage (following differentiation with all-trans retinoic acid). Effects on cell surface markers involved in macrophage activation and adhesion were also examined. Both soy and dairy ferments influenced U937 cytokine production with significant differences seen depending on the U937 differentiation stage. This suggests that potential immunomodulatory effects of fermented products can vary with respect to the target cell type and its stage of differentiation.

Harnessing functional food strategies for the health challenges of space travel—Fermented soy for astronaut nutrition

Astronauts face numerous health challenges during long-duration space missions, including diminished immunity, bone loss and increased risk of radiation-induced carcinogenesis. Changes in the intestinal flora of astronauts may contribute to these problems. Soy-based fermented food products could provide a nutritional strategy to help alleviate these challenges by incorporating beneficial lactic acid bacteria, while reaping the benefits of soy isoflavones. We carried out strain selection for the development of soy ferments, selecting strains of lactic acid bacteria showing the most effective growth and fermentation ability in soy milk (Streptococcus thermophilus ST5, Bifidobacterium longum R0175 and Lactobacillus helveticus R0052). Immunomodulatory bioactivity of selected ferments was assessed using an in vitro challenge system with human intestinal epithelial and macrophage cell lines, and selected ferments show the ability to down-regulate production of the pro-inflammatory cytokine interleukin-8 following challenge with tumour necrosis factor-alpha. The impact of fermentation on vitamin B1 and B6 levels and on isoflavone biotransformation to agluconic forms was also assessed, with strain variation-dependent biotransformation ability detected. Overall this suggests that probiotic bacteria can be successfully utilized to develop soy-based fermented products targeted against health problems associated with long-term space travel.