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Deciphering psychobiotics' mechanism of action: bacterial extracellular vesicles in the spotlight

FRONTIERS IN MICROBIOLOGY (2023)

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Review Nutrition & Dietetics

Probiotic supplements are effective in people with cognitive impairment: a meta-analysis of randomized controlled trials

Nanyang Liu et al.

Summary: This systematic review evaluated the effect of probiotic supplements on cognitive function. The study found that probiotic supplementation significantly improved cognitive function in individuals with cognitive impairment or Alzheimer's disease. However, it may be ineffective for individuals without cognitive impairment.

NUTRITION REVIEWS (2023)

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Article Microbiology

Escherichia coli-Derived Outer Membrane Vesicles Relay Inflammatory Responses to Macrophage-Derived Exosomes

Risa Imamiya et al.

Summary: Extracellular vesicles (EVs) released from macrophages infected with live Escherichia coli can induce inflammatory responses by uninfected macrophages. The inflammatory responses induced by EVs from macrophages infected with heat-inactivated E. coli or lipopolysaccharide are weaker compared to those induced by outer membrane vesicles (OMVs) from live E. coli. The proteins OmpA, GroL1, DegP, CirA, and FepA from E. coli are potential triggers of exosome-mediated inflammatory responses.

MBIO (2023)

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Article Biochemistry & Molecular Biology

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report

Michal Seweryn Karbownik et al.

Summary: Butyrate and indole-3-propionic acid, gut microbiota metabolites, have potentially beneficial effects on human brain function and are being tested as antidepressants. In a human astrocyte cell-line culture, a 10-minute incubation with 1-5 mM butyrate significantly increased ATP gliotransmitter release by 78%, mediated by cytosolic Ca2+ mobilization. Indole-3-propionic acid had no significant effect on gliotransmitter release. Further evaluation is needed to confirm these findings.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Multidisciplinary Sciences

Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice

Shan Yao et al.

Summary: The authors report a glycolytic deficit in mice under social stress, which is associated with depressive-like behaviors. They demonstrate that astrocytic LDHA affects neuronal excitability and the production of L-lactate, and this plays a role in preventing depressive-like behaviors. Mechanistic studies reveal that L-lactate promotes neuronal excitability through MCT2 and by inhibiting BK channels.

NATURE COMMUNICATIONS (2023)

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Article Neurosciences

Extracellular Vesicles from Gram-positive and Gram-negative Probiotics Remediate Stress-Induced Depressive Behavior in Mice

Juli Choi et al.

Summary: Chronic stress leads to changes in gut microbiota composition, which is related to depressive behavior. The study finds that certain probiotics can ameliorate stress-induced depressive-like behavior by restoring the changes in neurotrophic factors in the hippocampus.

MOLECULAR NEUROBIOLOGY (2022)

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Article Neurosciences

Psychobiotic Therapy: Method to Reinforce the Immune System

Karina Teixeira Magalhaes-Guedes

Summary: Psychobiotics are probiotic microorganisms that positively affect the central nervous system functions and improve the host's immune system. They have the potential to be a promising strategy for enhancing and maintaining the quality of life for healthy individuals as well as those suffering from anxiety/stress disorders, intestinal dysbiosis, and immune suppression.

CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE (2022)

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Article Cell Biology

Small Extracellular Vesicles from Peripheral Blood of Aged Mice Pass the Blood-Brain Barrier and Induce Glial Cell Activation

Diana M. Morales-Prieto et al.

Summary: Extracellular vesicles, specifically small EVs, are involved in neuroinflammation and neurodegenerative diseases. Aging brains show increased neuroinflammation and glial activation, which can be influenced by EVs. Our study demonstrates that sEVs from aged mice can cross the blood-brain barrier and induce glial cell activation in young animals.

CELLS (2022)

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Quality Control of Bacterial Extracellular Vesicles with Total Protein Content Assay, Nanoparticles Tracking Analysis, and Capillary Electrophoresis

Aleksandra Stec et al.

Summary: This study isolated EVs from Pectobacterium zantedeschiae culture media using different ultracentrifugation techniques and characterized them using BCA, NTA, and CE. The results showed that there was a satisfactory correlation between quantitative results obtained with BCA, NTA, and CE only for isolates obtained with the IDGUC. Moreover, NTA was found to be unable to provide reliable information on EVs quantity in samples isolated with UC and ICUC.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Cell Biology

Short chain fatty acids: Microbial metabolites for gut-brain axis signalling

Kenneth J. O'Riordan et al.

Summary: The role of the intestinal microbiota in regulating gut-brain axis signaling has gained attention in recent years. Understanding the relationship between the gut microbiota, its metabolites, and the brain is crucial for developing new therapeutic approaches, including identifying psychobiotics. Current research focuses on the effects of short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, on brain function, behavior, and physiology, and how these SCFAs enter the systemic circulation and can potentially impact the brain.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2022)

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Article Nutrition & Dietetics

Small Extracellular Vesicles in Milk Cross the Blood-Brain Barrier in Murine Cerebral Cortex Endothelial Cells and Promote Dendritic Complexity in the Hippocampus and Brain Function in C57BL/6J Mice

Fang Zhou et al.

Summary: This study assessed the transportation of sEVs across the blood-brain barrier and their accumulation in the brain, as well as their effects on neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice. The findings suggest that sEVs play a crucial role in these processes.

FRONTIERS IN NUTRITION (2022)

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Article Biochemistry & Molecular Biology

Extracellular Vesicles from 50,000 Generation Clones of the Escherichia coli Long-Term Evolution Experiment

David Laurin et al.

Summary: This study characterized the outer membrane vesicles (OMVs) released by evolved Escherichia coli clones after 50,000 generations of adaptation. The researchers found that the production and composition of OMVs varied along bacterial evolution. Tracking labeled OMVs showed that they fused with both ancestral and evolved cells, but in different proportions. These results suggest a potential role of OMVs in bacterial adaptation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Pharmacology & Pharmacy

Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-β axis

Zhang Yang et al.

Summary: This study found that Lactobacillus plantarum-derived extracellular vesicles (LEVs) could reduce apoptosis in ischemic neurons, potentially through the miR-101a-3p/c-Fos/TGF-beta axis. Additionally, has-miR-101-3p may be a potential marker for neurological recovery in ischemic stroke patients.

PHARMACOLOGICAL RESEARCH (2022)

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Editorial Material Microbiology

Early probiotics shape microbiota

Kaitlyn Oliphant et al.

Summary: Probiotics given to preterm infants have a long-term impact on their microbiota, emphasizing the importance of understanding the consequences for developmental outcomes.

NATURE MICROBIOLOGY (2022)

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Review Biochemistry & Molecular Biology

How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics

Kazunori Suda et al.

Summary: The gut microbiome influences the brain functions and psychological state of its host through the gut-brain axis, and gut dysbiosis is associated with mental illnesses. Animal experiments have shown that gut microbiota depletion leads to behavioral changes and pathological changes. Short-chain fatty acids like butyrate are associated with the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, potentially impacting neuronal development and synaptic plasticity. The influx of gut microbial components and systemic inflammation may cause neuroinflammation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Nutrition & Dietetics

Probiotics for the treatment of depression and anxiety: A systematic review and meta-analysis of randomized controlled trials

Regina El Dib et al.

Summary: This study suggests that probiotics may have a beneficial effect on depression and anxiety symptoms in clinical patients. However, the overall certainty of evidence is rated as low, and further large-scale studies with long-term follow-up are needed to confirm these findings.

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Article Biotechnology & Applied Microbiology

A next-generation probiotic: Akkermansia muciniphila ameliorates chronic stress-induced depressive-like behavior in mice by regulating gut microbiota and metabolites

Yang Ding et al.

Summary: The study demonstrated that Akkermansia muciniphila (AKK) significantly ameliorated depressive-like behavior induced by chronic stress, restored abnormal molecular levels related to depression, and altered chronic stress-induced gut microbial abnormalities. Additionally, untargeted metabolomics analysis identified potential biomarkers associated with the mechanisms underlying depression and the therapeutic effects of AKK.

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Review Biochemistry & Molecular Biology

The extracellular vesicle generation paradox: a bacterial point of view

Hannah M. McMillan et al.

Summary: Bacteria produce secreted vesicles that have both advantages and disadvantages, including improving adaptation and survival but also eliciting host immune responses and reducing viability. The production of vesicles is energetically costly, leading to questions about whether the benefits outweigh the costs.

EMBO JOURNAL (2021)

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Review Clinical Neurology

The effects of psychobiotics on the microbiota-gut-brain axis in early-life stress and neuropsychiatric disorders

Annie Tremblay et al.

Summary: Psychobiotics are considered as a potential avenue to modulate the communication between the gut and central nervous system, with a focus on early intervention for neuropsychiatric disorders. While animal studies have shown promise in countering stress effects during early developmental periods, evidence for psychobiotics efficacy in improving mental outcomes in NPDs other than depression in humans is limited.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2021)

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Article Multidisciplinary Sciences

Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

Katherine A. Partrick et al.

Summary: Probiotic administration alters gut microbial composition and promotes an anti-inflammatory profile, but these changes may not lead to reductions in behavioral responses to social stress.

SCIENTIFIC REPORTS (2021)

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Review Health Care Sciences & Services

A narrative review of relationship between gut microbiota and neuropsychiatric disorders: mechanisms and clinical application of probiotics and prebiotics

Huan Yang et al.

Summary: The gut microbiota plays a crucial role in maintaining health and disease mechanisms, influencing the central nervous system through the microbe-gut-brain axis and impacting the development and function of the brain. Probiotics and prebiotics are beneficial for regulating intestinal microecological balance and have a good preventive effect on neurological and mental diseases.

ANNALS OF PALLIATIVE MEDICINE (2021)

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Article Microbiology

Phage-Mediated Explosive Cell Lysis Induces the Formation of a Different Type of O-IMV in Shewanella vesiculosa M7T

Nicolas Baeza et al.

Summary: The study analyzed the secretion of membrane vesicles (MVs) from the Antarctic bacterium Shewanella vesiculosa M7(T) using high-resolution techniques, revealing an increase in MV secretion during different growth phases and activation of prophage-mediated explosive cell lysis. The findings highlighted a diversity of MVs, with a proposed new type termed explosive O-IMVs, suggesting potential different functions and emphasizing the importance of further development in bacterial MV separation techniques for deeper understanding.

FRONTIERS IN MICROBIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Role of Microbiota-Derived Extracellular Vesicles in Gut-Brain Communication

Carlos M. Cuesta et al.

Summary: This study discusses the critical role of bacterial extracellular vesicles (EVs) from the gut in the neuropathology of brain dysfunctions by modulating the immune response, leading to neuroinflammatory immune response activation. These vesicles, containing harmful bacterial contents, can cross tissue barriers and interact with immune receptors to produce cytokines and inflammatory mediators, ultimately causing brain impairment and behavioral dysfunctions.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Microbiology

Microbiota-host communications: Bacterial extracellular vesicles as a common language

Rogers A. Nahui Palomino et al.

Summary: Both gram-negative and gram-positive bacteria release extracellular vesicles (EVs) that contain components from their mother cells. Bacterial EVs are believed to mediate bacteria-host communications and play important roles in bacteria-bacteria and bacteria-host interactions. The understanding of bacterial EVs may lead to new therapeutics and diagnostics.

PLOS PATHOGENS (2021)

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Review Medicine, General & Internal

Understanding Why Post-Stroke Depression May Be the Norm Rather Than the Exception: The Anatomical and Neuroinflammatory Correlates of Post-Stroke Depression

Tissa Wijeratne et al.

Summary: The study analyzed the inflammatory basis of post-stroke depression, which results in cell death, persistent neuro-inflammation, and disrupted neuronal networks in mood-related brain regions. Furthermore, the anatomical structures related to post-stroke depression may involve complex circuitries in cortical and subcortical regions.

JOURNAL OF CLINICAL MEDICINE (2021)

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Review Biochemistry & Molecular Biology

Neuroprotective Function of High Glycolytic Activity in Astrocytes: Common Roles in Stroke and Neurodegenerative Diseases

Shinichi Takahashi

Summary: Astrocytes consume large amounts of glucose and produce lactate regardless of oxygen availability, playing a crucial role in providing energy substrates for neurons and protecting them against oxidative stress. The pentose-phosphate pathway (PPP) in astrocytes, which is involved in providing reduced glutathione for neurons, is significantly more active compared to neurons. Dysfunction of astrocytic glycolysis and the PPP have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Nutrition & Dietetics

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

Dinyadarshini Johnson et al.

Summary: The field of probiotics has grown significantly in recent years, showing potential in various health domains and in the treatment of depression. The promising role and mechanisms in treating depression provide important insights for probiotic research.

NUTRIENTS (2021)

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Review Nutrition & Dietetics

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

Yijing Chen et al.

Summary: Emerging evidence suggests that gut microbiota plays a crucial role in regulating brain activity and cognitive functions through the microbiota-gut-brain axis. The mechanisms by which gut microbiota regulate neurotransmitter production, transportation, and functioning are not well understood, nor are the effects of these interactions on normal brain functions and cognition. Dysbiosis of the microbiome can adversely affect cognitive function, particularly in neurodegenerative diseases like Alzheimer's and Parkinson's.

NUTRIENTS (2021)

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Article Multidisciplinary Sciences

Membrane vesicles of Lacticaseibacillus rhamnosus JB-1 contain immunomodulatory lipoteichoic acid and are endocytosed by intestinal epithelial cells

Kevin Champagne-Jorgensen et al.

Summary: Intestinal bacteria may influence host physiology by activating TLR2 and inducing IL-10 expression, and LTA appears to not be a necessary factor for MV endocytosis by IEC, in contrast to TLR2.

SCIENTIFIC REPORTS (2021)

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Review Psychiatry

Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultation

Kathrin Cohen Kadosh et al.

Summary: This study systematically reviewed and meta-analyzed microbiota-targeted interventions on anxiety in youth, finding limited evidence for the efficacy of psychobiotics for anxiety treatment in humans, particularly in youth. Further multidisciplinary research is needed to specify mechanisms, provide causal understanding, and address the wider context of anxiety treatment in youth.

TRANSLATIONAL PSYCHIATRY (2021)

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Article Neurosciences

Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease

Charysse Vandendriessche et al.

Summary: Increasing evidence suggests that extracellular vesicles (EVs) are important in the pathogenesis of Alzheimer's disease (AD), particularly through the release of EVs at the blood-cerebrospinal fluid interface. Studies in mice showed that A beta O can induce increased EV secretion, with the choroid plexus being a major source of CSF-EVs. These EVs from CP induced pro-inflammatory effects and inhibiting EV production with GW4869 protected against cognitive decline induced by A beta O.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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Gargi Dey et al.

Summary: As research progresses, probiotics are believed to have the potential to improve neurological conditions, especially symptoms of anxiety and depression. While more clinical trials are needed to clarify the exact mechanism of probiotic action, some established probiotic strains have shown potential as “psychobiotics”. New psychobiotic-based therapeutics are in the spotlight.

FEMS MICROBIOLOGY LETTERS (2021)

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Nicholas H. Pirolli et al.

Summary: Bacterial extracellular vesicles (BEVs) have been identified as potential signaling vectors for long-distance interkingdom communication within the gut-microbiota brain axis, with the ability to regulate brain gene expression and induce pathology in neuroinflammatory and neurodegenerative conditions. BEVs also have therapeutic properties that can be utilized in probiotic therapy, drug delivery, and vaccine development.

ADVANCED BIOLOGY (2021)

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Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

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Review Clinical Neurology

Effects of Probiotics on Depressive or Anxiety Variables in Healthy Participants Under Stress Conditions or With a Depressive or Anxiety Diagnosis: A Meta-Analysis of Randomized Controlled Trials

Limin Chao et al.

FRONTIERS IN NEUROLOGY (2020)

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The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders

Linoy Mia Frankiensztajn et al.

CURRENT OPINION IN NEUROBIOLOGY (2020)

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial

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JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY (2020)

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Masanori Toyofuku et al.

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