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Role of the Intestinal Microbiome, Intestinal Barrier and Psychobiotics in Depression.
Trzeciak, P, Herbet, M
Nutrients. 2021;13(3)
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Major depressive disorder (MDD) is a disorder with feelings of depressed mood or loss of interest or pleasure alongside several other symptoms such as weight or appetite changes, difficulty sleeping and an inability to think or concentrate. The development of MDD is not fully understood and may involve several different factors such as the gut microbiome. The gut microbiome may be involved as it can communicate with the brain in a bidirectional fashion, known as the gut-brain axis. This review study aimed to summarise the data on the use of probiotics thought to confer benefits in the brain, known as psychobiotics. Depression is thought to involve aspects of imbalances in brain signalling molecules, stress hormones, and free radicals and inflammation. One of the newest ideas suggests that the gut microbiome may have a role. Individuals with depression have shown to have altered composition of gut microbiota, which may have an impact in several ways. Alterations in vitamin production, altered intestinal barrier function and poor diet during disease, may all contribute to the development of MDD. Psychobiotics may be of benefit to symptoms of depression shown in numerous animal and human studies. It was concluded that there are several ways that the microbiota may be involved in the development of depression. This study could be used by healthcare professionals to justify the introduction of psychobiotics as an adjuvant to standard therapy for MDD, to relieve symptoms.
Abstract
The intestinal microbiota plays an important role in the pathophysiology of depression. As determined, the microbiota influences the shaping and modulation of the functioning of the gut-brain axis. The intestinal microbiota has a significant impact on processes related to neurotransmitter synthesis, the myelination of neurons in the prefrontal cortex, and is also involved in the development of the amygdala and hippocampus. Intestinal bacteria are also a source of vitamins, the deficiency of which is believed to be related to the response to antidepressant therapy and may lead to exacerbation of depressive symptoms. Additionally, it is known that, in periods of excessive activation of stress reactions, the immune system also plays an important role, negatively affecting the tightness of the intestinal barrier and intestinal microflora. In this review, we have summarized the role of the gut microbiota, its metabolites, and diet in susceptibility to depression. We also describe abnormalities in the functioning of the intestinal barrier caused by increased activity of the immune system in response to stressors. Moreover, the presented study discusses the role of psychobiotics in the prevention and treatment of depression through their influence on the intestinal barrier, immune processes, and functioning of the nervous system.
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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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Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.
Reiter, A, Bengesser, SA, Hauschild, AC, Birkl-Töglhofer, AM, Fellendorf, FT, Platzer, M, Färber, T, Seidl, M, Mendel, LM, Unterweger, R, et al
Nutrients. 2020;12(9)
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Major depressive disorder (MDD) is a disease with multiple aetiology and symptoms that can end in death due to suicide. A biological imbalance in free radicals and inflammatory molecules have been associated with depression and diseases such as obesity which are often associated with MDD. Probiotics may potentially be able to redress this imbalance through several mechanisms. The aim of this randomised placebo-controlled trial was to assess the effect of probiotics on mood, brain function, gut microbiome and inflammation genes in 61 individuals with MDD over 4 weeks. The results showed that probiotic intake improved expression of some but not all of the assessed inflammatory genes and it was concluded that positive effects of probiotics on inflammation may mean that they are of benefit to those with MDD. This study could be used by healthcare professionals who are looking at additional, non-pharmacological ways of supporting patients with MDD.
Abstract
Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.
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Reductions in anti-inflammatory gut bacteria are associated with depression in a sample of young adults.
Liu, RT, Rowan-Nash, AD, Sheehan, AE, Walsh, RFL, Sanzari, CM, Korry, BJ, Belenky, P
Brain, behavior, and immunity. 2020;88:308-324
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Alterations to the gut microbiota may be associated with depression and anxiety disorders through a pathway known as the gut-brain axis. Inflammation may be the mediator between the two, as individuals with major depressive disorder (MDD) have reported high levels of inflammation, which the gut microbiota may have the capacity to protect against. This observational study of the gut microbiota of 90 young adults with MDD and 47 healthy controls aimed to determine the relationship between inflammatory gut microbiota and symptoms of depression. The results showed changes to several species of gut microbiota in those with MDD and that the level of change was related to MDD symptom severity. These changes were observed even in those taking psychotropic medications. Changes at the taxonomic level indicated that those with higher symptoms of depression had more pronounced differences compared with healthy controls. Although the observed differences were indicative of an inflammatory microbiome, no changes were observed in blood markers of inflammation between those individuals with MDD and healthy controls. It was concluded that the gut microbiome of individuals with MDD was different from healthy individuals in favour of an inflammatory environment. This study could be used by healthcare professionals to understand that the status of the gut microbiota may be an important measure in individuals with MDD and that a treatment plan to ensure gut health is considered may help with symptoms of depression.
Abstract
We assessed the gut microbiota of 90 American young adults, comparing 43 participants with major depressive disorder (MDD) and 47 healthy controls, and found that the MDD subjects had significantly different gut microbiota compared to the healthy controls at multiple taxonomic levels. At the phylum level, participants with MDD had lower levels of Firmicutes and higher levels of Bacteroidetes, with similar trends in the at the class (Clostridia and Bacteroidia) and order (Clostridiales and Bacteroidales) levels. At the genus level, the MDD group had lower levels of Faecalibacterium and other related members of the family Ruminococcaceae, which was also reduced relative to healthy controls. Additionally, the class Gammaproteobacteria and genus Flavonifractor were enriched in participants with MDD. Accordingly, predicted functional differences between the two groups include a reduced abundance of short-chain fatty acid production pathways in the MDD group. We also demonstrated that the magnitude of taxonomic changes was associated with the severity of depressive symptoms in many cases, and that most changes were present regardless of whether depressed participants were taking psychotropic medications. Overall, our results support a link between MDD and lower levels of anti-inflammatory, butyrate-producing bacteria, and may support a connection between the gut microbiota and the chronic, low-grade inflammation often observed in MDD patients.
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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.
Karakula-Juchnowicz, H, Rog, J, Juchnowicz, D, Łoniewski, I, Skonieczna-Żydecka, K, Krukow, P, Futyma-Jedrzejewska, M, Kaczmarczyk, M
Nutrition journal. 2019;18(1):50
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Major depressive disorder (MDD) has historically been recognised as a brain disease, however more recently it is being recognised as a whole-body disorder. The immune system and the gut microbiota have been implicated in MDD with particular focus on the gut wall integrity and the resultant immune reaction and its influence on the brain. Gluten may incite an immune reaction in certain individuals and a gluten free diet may be of benefit to symptoms of depression in those who have gluten-related disorders. This randomised prospective control trial of 120 patients with MDD aims to determine the effect of a gluten free diet and probiotic supplementation in symptom management over 12 weeks. As this was a prospective study, no results were achieved. However, the study does indicate that randomised control trials on the effect of diet in MDD are advancing and there may be scientifically proven avenues to support standard therapies.
Abstract
BACKGROUND Current 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. METHODS A 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. DISCUSSION Microbiota 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 REGISTRATION NCT03877393 .