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Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.
Wauters, L, Van Oudenhove, L, Accarie, A, Geboers, K, Geysen, H, Toth, J, Luypaerts, A, Verbeke, K, Smokvina, T, Raes, J, et al
Gut microbes. 2022;14(1):2031695
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Previous research has shown a bidirectional relationship between the gut and psychological stress, which could be mediated by intestinal permeability followed by an immune and inflammatory response. However, the exact mechanisms of this relationship are yet to be elucidated. This randomised, double-blind, placebo-controlled trial evaluated the beneficial effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress markers during a public speech in healthy students. Participants consumed either milk containing Lactobacillus rhamnosus CNCM I-3690 or acidified milk twice daily for four weeks to assess subjective and objective stress markers and markers of intestinal permeability. Lactobacillus rhamnosus CNCM I-3690 reduced the stress-induced hyperpermeability to mannitol and subjective stress markers (State-Trait Anxiety Inventory/ STAI). A subgroup of healthy students with stress-induced cortisol >P90 of baseline showed a reduction in perceived stress score following Lactobacillus rhamnosus CNCM I-3690 intervention. To evaluate the additional effects of Lactobacillus rhamnosus CNCM I-3690 on stress and gut health, further robust studies are needed. Healthcare professionals can use the findings of this study to understand the anxiolytic effects of Lactobacillus rhamnosus CNCM I-3690.
Abstract
Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.
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Patti & Michael Discuss The Gut-Brain Axis (Rebroadcast)
Genova Diagnostics' podcast, The Lab Report, is focused on functional & integrative medicine, specialty laboratory diagnostics, and natural therapeutics. Join hosts Michael Chapman, ND,Patti Devers, DO, and assorted guests, as they bring their own unique style to the health & wellness discussion. It is aimed at providing the same type of educational content that Genova is well-known for, but to the larger audience of functional & integrative practitioners of all experience levels.
2021
Abstract
In this episode, Patti and Michael discuss some of the mechanisms by which this axis sends and receives those signals. They also talk about the importance of addressing both when optimizing health. The commensal bacteria in our gut and their metabolites can directly affect our memory and mood, while our brain can alter bacterial patterns and GI function. They also chat about the communication mechanisms from the GI tract to the brain, how the brain affects the gut and how to support treatment - also using Genova diagnostics functional tests. To conclude, they talk about the latest research in regards to psychobiotics and their role in influencing neurotransmitter production and, consequently, our mood.
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Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression.
Huang, F, Wu, X
Frontiers in cell and developmental biology. 2021;9:649103
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The causes of anxiety and depression are unclear, but growing evidence points to a role of the gut microbiota. One possible way that the gut microbiota may have an influence on mental health is through a group of chemical messengers in the brain, known as neurotransmitters. This review summarised the research surrounding neurotransmitters and gut microbiota. The review began by looking at research in animal models and the roles of various neurotransmitters and how they may be influenced by the gut microbiota. The neurotransmitters outlined were serotonin, dopamine, and noradrenaline and it was stated that there is evidence that gut microbiota may be able to influence them alleviating anxiety and/or depression, however there was limited evidence with noradrenaline. It was concluded that there is a close connection between the gut microbiota and anxiety and depression. There is more research needed in humans, as most work has been completed in animal models. This paper could be used by healthcare professionals to understand the role of the gut microbiota in mental health disorders and the importance of gut health in individuals suffering from these.
Abstract
Anxiety and depression are highly prevalent mental illnesses worldwide and have long been thought to be closely associated to neurotransmitter modulation. There is growing evidence indicating that changes in the composition of the gut microbiota are related to mental health including anxiety and depression. In this review, we focus on combining the intestinal microbiota with serotonergic, dopaminergic, and noradrenergic neurotransmission in brain, with special emphasis on the anxiety- and depression-like behaviors in stress-related rodent models. Therefore, we reviewed studies conducted on germ-free rodents, or in animals subjected to microbiota absence using antibiotics, as well as via the usage of probiotics. All the results strongly support that the brain neurotransmitter modulation by gut microbiota is indispensable to the physiopathology of anxiety and depression. However, a lot of work is needed to determine how gut microbiota mediated neurotransmission in human brain has any physiological significance and, if any, how it can be used in therapy. Overall, the gut microbiota provides a novel way to alter neurotransmitter modulation in the brain and treat gut-brain axis diseases, such as anxiety and depression.
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Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis.
Sjöstedt, P, Enander, J, Isung, J
Frontiers in psychiatry. 2021;12:682868
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In preceding centuries common thought was that psychiatric disorders originated from the gut. In later years this concept was replaced by the idea of it being a disorder of the brain and that an imbalance of neurotransmitters is the cause of depression and other psychiatric conditions (monoamine hypothesis). This theory has been dominating psychiatric research for the past decades, and selective serotonin reuptake inhibitors (SSRIs) have become a widespread treatment option for psychological disorders. Despite their benefits, their use also presents clinical challenges such as treatment resistance, side effects or loss of effect. Consequently, the monoamine hypothesis has become disputed with other pathophysiological mechanisms having been proposed in recent years. With an appreciation of the pathophysiological complexities, this opinion-based article sought to present alternate views and to suggest areas for future research regarding psychiatric disorders, SSRIs and the gut-brain axis. The gut-brain axis has complex communication and signalling pathways in essence, the gut microbiome can exert significant effects on emotions, behaviours, metabolic risks, and the metabolism of drugs. Nerve cells of the gut also generate substantial amounts of serotonin for use within the gut. Equally, the gut microbiome produces and uses serotonin. It appears that some of the side effects associated with SSRIs, such as weight gain, are mediated via the gut microbiome. Further evidence suggests that SSRIs and several other psychotropic drugs exert antimicrobial action, which can alter the balance and integrity of the gut microbiome. Therefore, it would be valuable to further investigate the impact of long-term SSRI use on the microbial constellation in the gut and whether certain microbiome patterns could help predict treatment responsiveness or side effects, that may be manageable via microbiome manipulation. The authors believe that an advanced understanding of the dynamics of the gut microbiome could provide better and personalized treatment options for mental health conditions. This article provides a brief insight into current thoughts and theories of psychiatric disorders, SSRIs and the gut.
Abstract
The monoamine hypothesis of psychopharmacology has been dominating the biological psychiatric research field for decades. Currently psychiatric research has increasingly appreciated psychiatric disorders and suicidal behavior as being highly complex and multi-etiological. In this pathway the gut microbiome and its interrelationship with the brain is gaining traction. The usage of selective serotonin reuptake inhibitors (SSRIs) is increasing in the general population. This is due to their effect on a broad range of psychiatric disorders, and their favorable side effect profile. Still, there are enigmatic aspects about SSRIs, such as the difficulty to predict effect in individual patients, inter-individual differences in side effect, tachyphylaxis (a sudden loss of response to a certain drug), and to date, uncertainties on how they exert their clinical effect. A majority of the serotonin in the human body is produced within the gut, and SSRIs affect enteric neurons. They also exhibit antimicrobial properties that comes with the potential of disrupting microbial hemostasis. We propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted. With this article, together with similar articles, we would like to provide a hypothetical framework for future studies within this field. We believe that this would have the potential to provide a paradigm shift within the field of psychopharmacology, and result in findings that potentially could contribute to the development of a more personalized and tailored treatment.
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Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder.
Johnson, D, Thurairajasingam, S, Letchumanan, V, Chan, KG, Lee, LH
Nutrients. 2021;13(5)
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A bi-directional communication between the brain and the microbiome of the gut may exist, known as the microbiome-gut-brain axis (MGBA). The role of this and the use of probiotics in relation to many psychiatric and neurological disorders is being increasingly researched. This review aimed to summarise the research on the use of probiotics for the treatment of mental health disorders and major depressive disorder (MDD). Probiotics and their use were summarised concluding that they have a diverse range of health benefits due to their anti-inflammatory, antipathogenic and antimicrobial actions. Imbalances in the four major phyla of gut bacteria; Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria may have a major role in the development of MDD. Probiotics may have several mechanisms through which they benefit MDD and decreased inflammation in the brain, increased production of chemicals involved in brain signalling and decreased stress hormones, were all implicated. It was concluded that probiotics have mental health benefits, however gaps in the evidence from studies needs to be addressed. This study could be used by healthcare professionals to understand the role of probiotics in the treatment of mental health disorders and in particular MDD.
Abstract
The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota-gut-brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.
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Chronic Food Antigen-specific IgG-mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder.
Tao, R, Fu, Z, Xiao, L
Genomics, proteomics & bioinformatics. 2019;17(2):183-189
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The prevalence of major depressive disorder (MDD) among adolescents has been on the rise recently. A high level of systemic low-grade inflammation is found in the serum of MDD adults, which is believed to interfere with neurotransmitter metabolism, resulting in symptoms of depression. Furthermore, disruption of the blood-brain barrier may inhibit neurotransmitter metabolism. One hundred and eighty-four adolescents with moderate MDD were evaluated against the same number of healthy controls to determine their serum levels of markers of inflammation, homocysteine, food sensitivity, histamine, and histamine metabolism. The study found that histamine levels and food antigen-specific antibodies in MDD adolescent patients were significantly higher than those in the control group. Increasing histamine levels, food-specific IgG levels, and S100 calcium-binding protein B levels suggest blood-brain barrier leakage may contribute to adolescent depression. There is still much to be learned about the pathophysiology of MDD, and further studies are needed to elucidate the mechanisms involved. The results of this study can be used by healthcare professionals to understand the role of histamine and food sensitivities in the development of adolescent depression rather than low-grade inflammation.
Abstract
Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
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Small talk: microbial metabolites involved in the signaling from microbiota to brain.
Caspani, G, Swann, J
Current opinion in pharmacology. 2019;48:99-106
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The gut-brain axis (GBA) is the communication network between the gastrointestinal tract and the central nervous system. An array of gut bacteria-derived metabolites mediates this interaction between the gastrointestinal system and the brain, influencing physiological and pathological processes in direct and indirect ways. Thus a variation in the gut microbiome can alter the functional capacity and output of the gut-brain-communication. In this review, the authors summarise key bacterial metabolites from the gut and their effect on the brain. Addressed are short-chain fatty acids, their impact on gut and brain barrier integrity, their role in appetite regulation, and their association with anxiety and depressive disorders amongst other aspects. Secondly, bile acids, which are processed by the microbiome, can activate several receptors. And thus divergence gut bacteria can alter the composition of bile acids and change their signalling capacity. Bile acids can also directly modify gut and blood-brain barrier function and may carry a signalling role in the brain. A few neurotransmitters are covered in this article, as several types of gut bacteria synthesize neurotransmitters, such as serotonin and dopamine. Though, it is uncertain whether all gut-derived neurotransmitters can reach the brain. However, certain GABA-producing bacteria have been shown to elicit higher GABA levels in the brain. The microbiota can also be involved with the conversion of neurotransmitters such as dopamine. The final section briefly capture the evidence of other brain health-relevant molecules derived from the intestinal microbiota, including Lipopolysaccharides, choline, lactate and B-Vitamins. This review yields a short and comprehensive summary highlighting the many ways the gut can influence brain function and health and could be of interest to those providing mental health support in light of gut function.
Abstract
The wealth of biotransformational capabilities encoded in the microbiome expose the host to an array of bioactive xenobiotic products. Several of these metabolites participate in the communication between the gastrointestinal tract and the central nervous system and have potential to modulate central physiological and pathological processes. This biochemical interplay can occur through various direct and indirect mechanisms. These include binding to host receptors in the brain, stimulation of the vagus nerve in the gut, alteration of central neurotransmission, and modulation of neuroinflammation. Here, the potential for short chain fatty acids, bile acids, neurotransmitters and other bioactive products of the microbiome to participate in the gut-brain axis will be reviewed.