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

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

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required

Cheese Fermented with Human-Derived Limosilactobacillus reuteri DSM 17938 and Mushroom Powders: A Novel Psychobiotic Food with Enhanced Bioactivity and Sensory Acceptability

Fermented foods containing psychobiotics are of growing interest among food scientists. Human-derived Limosilactobacillus reuteri DSM 17938, a gut symbiont and potential psychobiotic strain, has been shown to exhibit the following health benefits: anti-inflammation and GABA-production capacity, as well as modulation of pathogen and cancer cell growth. The aim of this research was to develop an acid-coagulated fresh soft quark-type cheese, fermented with L. reuteri DSM 17938, with enhanced bioactivity, sensory acceptability, and overall likeability. Psychobiotic-containing cheeses represent the food of a new generation, so it is of great importance to gain the trust of the consumers. To develop a familiar taste, cheese samples were enriched with mushroom powders of Agaricus bisporus and Pleurotus ostreatus. A high abundance of lactic acid bacteria was maintained in all cheese samples (>log 7.64 CFU/mL), while cheese extracts exhibited cytotoxicity to colon cancer cell line HCT116 (up to 30.96%) in vitro. Additionally, cheese samples provided a favorable medium for the growth of the probiotic Escherichia coli Nissle 1917 (>log 7.11 CFU/mL). Sensory evaluation revealed high scores for all samples (up to 97.21% of maximum overall quality). The survey conducted in this study offered insights into consumer willingness to try products containing psychobiotics. This study demonstrates the potential for the successful development of fermented food products with L. reuteri DSM 17938, which exhibits all the desired traits that consumers may receive well. Further research is required to explore the potential health benefits of these innovative food products

Psychobiotics Regulate the Anxiety Symptoms in Carriers of Allele A of IL-1β Gene: A Randomized, Placebo-Controlled Clinical Trial

Background. Probiotic oral intake, via modulation of the microbiota-gut-brain axis, can impact brain activity, mood, and behavior; therefore, it may be beneficial against psychological distress and anxiety disorders. Inflammatory cytokines can influence the onset and progression of several neurodegenerative mood disorders, and the IL-1β rs16944 SNP is related to high cytokine levels and potentially affects mood disorders. The aim of this study was to examine the combined effect of IL-1β polymorphism and probiotic administration in mood disorder phenotypes in the Italian population. Methods. 150 subjects were randomized into two different groups, probiotic oral suspension group (POSG) and placebo control group (PCG), and received the relative treatment for 12 weeks. Psychological profile assessment by Hamilton Anxiety Rating Scale (HAM-A), Body Uneasiness Test (BUT), and Symptom Checklist 90-Revised (SCL90R) was administered to all volunteers. Genotyping was performed on DNA extracted from salivary samples. Results. After 12 weeks of intervention, a significant reduction of HAM-A total score was detected in the POSG (p < 0.01), compared to the PCG. Furthermore, IL-1β carriers have moderate risk to develop anxiety (OR = 5.90), and in POSG IL-1β carriers, we observed a reduction of HAM-A score (p = 0.02). Conclusions. Consumption of probiotics mitigates anxiety symptoms, especially in healthy adults with the minor A allele of rs16944 as a risk factor. Our results encourage the use of probiotics in anxiety disorders and suggest genetic association studies for psychobiotic-personalized therapy

The role of probiotics in the treatment of depressive disorders. A critical review

Depressive disorders are a widespread problem in modern medicine. According to current data from the World Health Organisation, an estimated 280 million people worldwide suffer from depression. In recent years, there have been reports of a correlation between the composition of the gut microbiota and the development of depressive disorders and attempts to modify it through the use of psychobiotics. The literature from the PubMed database published between 2018-2023 has been explored. 596 articles were selected based on the keywords "probiotics" and "depression". Six randomized clinical trials were finally included in the analysis. As defined elsewhere, psychobiotics are probiotic bacteria which supplemented in adequate amounts, interact with the gut-brain axis and show beneficial effects on patients' mental health. Results from recent RCTs suggest that daily probiotic supplementation significantly reduces the severity of depression compared to placebo (p&lt;0.05). Additionally, this effect may be enhanced by the combined use of a probiotic with a prebiotic. Furthermore, some researchers indicate that probiotics may lead to significant improvements in cognitive function in patients suffering from depressive disorders. In conclusion, intestinal dysbiosis may be an important factor leading to the development of mental illness. Results of recent studies suggest that specific strains of probiotic bacteria may offer therapeutic benefits in the treatment of the aforementioned disorders. However, further clinical studies are needed to objectively confirm the relationship between gut microbiota composition and the development of depression

Effect of a multistrain probiotic (Lactoflorene® Plus) on inflammatory parameters and microbiota composition in subjects with stress-related symptoms

Stress affects the immune system and intestinal microbiota composition and can lead to imbalance between pro- and anti-inflammatory cytokines or to uncontrolled production of cytokines. The effect of emotional stress on secretory IgA levels also indicates that stress decreases mucosal integrity. Our aim was to evaluate whether a probiotic product (Lactoflorene® Plus) can prevent alterations in the immune response associated with self-reported stress and microbiota composition. Healthy adult volunteers who self-reported psychological stress were enrolled and randomised into a placebo and a probiotic group. Salivary stress markers (α-amylase, cortisol, chromogranin A) and immunological parameters (sIgA, NK cell activity, IL-8, IL-10, TNF-α) in feces and the composition of intestinal microbiota were evaluated. Administration of the product did not exert a direct effect on the salivary stress markers or NK cell activity but did reduce abdominal pain and increase faecal IgA and IL-10 levels. The probiotic product induced a moderate increase in Bifidobacterium and Lactobacillus spp., as expected, and in Faecalibacterium spp., and decreased the size of the Dialister spp. and Escherichia and Shigella populations. Administration of the product helped protect the mucosal barrier by supporting the number of short-chain fatty acid producers and decreasing the load of potentially harmful bacteria, thus reducing intestinal inflammation and abdominal discomfort. ClinicalTrials.gov: NCT03234452

Clinical Potential of Microbial Strains, Used in Fermentation for Probiotic Food, Beverages and in Synbiotic Supplements, as Psychobiotics for Cognitive Treatment through Gut–Brain Signaling

Pure and viable strains of microorganisms identified and characterized as probiotic strains are used in the fermentation process to prepare probiotic food and beverages. These products are sources of nutrition and help in the maintenance of gut microflora. The intake of food products prepared with the use of probiotic microorganisms and containing their metabolites and whole microbial cells can be considered as a natural formulation of synbiotic products with prebiotic substrates and culture. Other than through the intake of fermented food and beverages, probiotic microorganisms can be taken through a supplement, which is a complementary form prepared by combining separate sources of prebiotic substrates and specific probiotic cultures. Whether a fermented solid food or beverage, both the components in the product are in a synergistic relationship and contribute to several health benefits at a lower cost. The aim of this article is to review the relevant literature and present the outcomes of recent studies which have been conducted to explore the clinical potential of probiotic strains and their effect on psychological conditions. Studies have shown the relationship between gut microbiota and the brain, and their interaction through signaling. The studies have concluded that the gut–brain axis can be manipulated with the intake of probiotic foods or synbiotic supplements containing specific probiotic strains accompanied with their complementary prebiotics for the enhanced sustainability of healthy GIT microflora

Sedative-like effect of intraperitoneal GABA administration in the open field test

Gamma-Amino Butyric Acid (GABA) is the main inhibitor neurotransmitter of the Central Nervous System (CNS). Its peripheral administration has been matter of discussion. On the one hand, it has been reported that it does not cross the Blood-Brain Barrier (BBB), and, on the other hand, it has been associated with multiple therapeutic regimens and supplements by peripheral administration. The aim of the present study is to elucidate the possibility of a central sedative effect when administered peripherally. An experimental cohort of 90-day-old Holtzman male rats weighing 240-270 g was used. It was divided into 2 groups: saline-controls (n = 9) and GABA treated rats (12.5 mg/kg, n = 9). Both groups were intraperitoneally injected. The motor behavioral patterns displayed in the Opto Varimex (OVM) were studied. Vertical, horizontal, ambulatory and non-ambulatory movements and the number of movements were recorded in an automated way. Horizontal movements constitute the integration of ambulatory and non-ambulatory movements. Student t test was used comparing groups. In this experiment, there were non-significant downward trends in vertical, ambulatory, non-ambulatory and number of movements. Ambulatory and non-ambulatory tendencies acquired significance when treated together as horizontal movements (p < 0.05). We may conclude that peripheral administration of GABA produced a decrease of the horizontal movements in the open field test. It may be interpreted as a sedative effect, suggesting a passage of GABA through BBB, with central effects. However, there are several alternative possibilities to explain present findings. Other experiments will elucidate the implications or scope of the present findings.Fil: Gargiulo, Augusto Pascual Ítalo. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Marquez Herrero, Santiago. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Romanowicz, Esteban Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Guevara, Manuel Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Landa, Adriana Inés. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Lafuente, José Vicente. Universidad del País Vasco; EspañaFil: Mesones, Humberto Luis. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Fundación Instituto de Neurobiología; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentin