Microbiota and Mental Health

Given their enormous potential to enhance human health, probiotics are the focus of intense study efforts and constitute a multi-billion dollar global industry. Probiotics may also have the potential to be a cutting-edge, adaptable therapy for depression, as mental health is a crucial area of healthcare that currently has few risky treatment choices. A precision psychiatry-based strategy utilizing probiotics may be suitable for treating clinical depression, a prevalent and possibly crippling disease. Although we still don't fully comprehend it, Johnson et al. (2023) propose that probiotics may present a therapeutic strategy that can be tailored for particular people with their special collection of traits and health problems. Probiotics can change the way depressive disorders are treated because, in principle, they are perfect as stand-alone therapeutics for moderate major depressive disorder (MDD) and as adjuvant therapeutics for major MDD. The microbiota-gut-brain axis (MGBA) mechanisms involved in the pathophysiology of depression provide a sound foundation for using probiotics as a therapy for the illness. Although there are many different probiotics available and virtually endless therapeutic combinations, the authors aim in this review to focus on the most popular and extensively researched strains, namely Lactobacillus and Bifidobacterium, and to compile the evidence supporting their use in people with MDD. Clinicians, researchers, and businesspeople are vital participants in investigating this novel concept. [NPID: Probiotics, depression, psychiatry, precision, gut microbes, Major Depressive Disorder]

In this study by Badri et al. (2021), the authors used data from a Quality of Life survey conducted in the city of Abu Dhabi (September 2019 - March 2020, participants aged 15 and above, n = 72,034) to investigate the links between how we perceive health, happiness, healthy eating habits, psychological symptoms of mental health and physical activity. Analysis of participant responses to the online survey revealed three distinct mental variables as pathways to perceived happiness, namely, “having lots of energy,” “feeling calm and peaceful,” and “feeling downhearted and depressed.” Happiness also correlated positively with self-rated health, and positively related to “often doing physical activities.” On the other hand, mental variables relating to “often feeling rushed or pressed for time” are linked directly to self-rated health only. Finally, the consumption of healthy food was substantially linked to the self-perception of health and happiness domains. The authors conclude by discussing their study’s limitations, and recommendations for future research, and present these findings to improve policymakers' understanding of self-rated health and happiness to guide efficient decision-making. [NPID: Eating healthy, happiness, mental health, path analysis, physical activities, self rated health]

Studies have shown how probiotics enhance mood in healthy individuals, which postulates that probiotics can play a role as therapeutic adjuncts and as a non-invasive intervention in the treatment of clinically diagnosed depression and in the prevention of depressive moods in otherwise healthy populations. In this double-blind, placebo-controlled study by Marotta et al. (2019), the authors investigated the impact of probiotics on mood changes (namely, the cognitive responses towards sad moods, anxiety and depression), quality of sleep and personality dimensions related to mood, in a population of 38 healthy individuals divided into either a control or experimental groups. The study participants received either a placebo or a daily probiotic mixture (composed of Lactobacillus fermentum LF16, L. rhamnosus LR06, L. plantarum LP01, and Bifidobacterium longum BL04) for a period of six weeks, and had their personality dimensions, mood and quality of sleep investigated at four time points (prior to the study, at 3 weeks, at 6 weeks and three weeks after study conclusion). The authors noted a substantial enhancement of mood in the intervention group, where administering the probiotic mixture led to a decrease in anger, fatigue, depression and enhanced sleep quality. The authors conclude that their results align with published evidence on the beneficial impact of probiotics on mood, and postulate that administering probiotics may help enhance mood, sleep quality and overall psychological well-being. [NPID: Mood disorders, probiotics, depression, anger, anxiety, placebo-control]

The impact of probiotics on brain functionality in healthy older adults is not well understood, despite probiotics holding promise in improving depression and cognitive derangements through modulating the gut-brain axis, as seen in both human and animal models. In this randomized, double-blind, placebo-controlled multicenter trial by Kim et al. (2021), the authors investigated the impact of probiotics on mood and cognition in a population of 63 healthy, community-dwelling older adults (≥65 years old). The participants were given either a placebo or an intervention containing two probiotic bifidobacterium species (B. bifidum [BGN4] and B. longum [BORI]) for 12 weeks. The cerebral function was evaluated using a validated stress questionnaire, the Consortium to Establish a Registry for Alzheimer's disease, the Geriatric depression scale, the Satisfaction with life scale, and the Positive affect and negative affect schedule. In addition, the gut microbiome population was evaluated using RNA sequencing and bioinformatics, while serum brain-derived neurotrophic factor (BDNF) was measured using ELISA. Analysis of the results revealed a substantial decrease in inflammation-associated gut microbiota, enhanced mental flexibility and stress scores, and raised BDNF levels, compared to Placebo. The rise in BDNF levels was also associated with a substantial reduction in the population of Eubacterium and Clostridiales species. The authors conclude that probiotics cause a shift in the gut microbiome population, help ameliorate stress and enhance mental flexibility in older adults, commenting that these results highlight the value of exploring probiotic-based health interventions to improve the health status of older adults. [NPID: Cognitive function, gut microbiota, healthy older adults, mood status, probiotics, RCT]

Probiotics are postulated to alleviate a myriad of health problems, such as immunologic and metabolic diseases, however, their impact on brain function remains poorly understood. In this cross-sectional study by Kim & Shin (2019), the authors investigated the relationship between probiotic food intake and depression in a sample of 26,118 individuals (19-64 years of age) derived from the Korean National Health and Nutrition Examination Survey (KNHANES, 2012-2016). The participants accounted for their probiotic intake through a food frequency questionnaire, while depression was investigated using a Patient Health Questionnaire (PHQ-9) and self-reported clinical diagnostic data. Analysis of the results revealed that men consuming the highest amounts of probiotic foods were substantially less likely to report clinical depression and had the lowest depression severity PHQ-9 scores. No substantial relationship was found with probiotic consumption and depression in women. The authors conclude that their results show a beneficial effect on depression with the consumption of probiotic foods in men, and that additional research is necessary to understand the mechanisms governing the relationship between probiotics and depression. [NPID: Depression, KNHANES, probiotics]

A novel dietary intervention for major depressive disorder (MDD) involves modulation of the gut microbiome to influence the microbiota-gut-brain (MGB) axis, an integral part of the pathology underlying physiological and behavioral derangements seen in MDD. Schaub et al. (2022) conducted this randomized controlled trial investigating the impact of a short-term, high-dose probiotic intervention on reducing symptoms of depression, neural, and gut microbiome derangements in MDD patients, a first of its kind. Patients suffering from depression at the time of the study were divided into two groups, and received either a multi-strain probiotic supplement (N = 21) or placebo (N = 26) for 31 days as an adjunct to their current treatment regimen. Participants were assessed for treatment effects before the study, immediately after study conclusion and once more after 4 weeks. The Hamilton Depression Rating Scale (HAM-D) was used to evaluate depression, while microbiome profiling and neuroimaging investigated MGB axis changes. The results demonstrated a significant reduction in HAM-D scores in addition to increased microbiome diversity (with an expansion of the genus Lactobacillus linked to the observed reduction in the symptoms of depression, compared to other genera) with probiotic treatment compared to placebo. Furthermore, a reduction in putamen activation triggered by neutral faces (a finding seen in MDD) was also substantially reduced with probiotic treatment. The authors conclude that adjunctive therapy with probiotics helps in reducing the symptoms of depression (as evident by lower HAM-D scores), alter the gut microbiome, and brain activity of depressed patients, thus highlighting the key part played by MGB axis in MDD and the promise it holds as a therapeutic target of microbiome-based interventions, which are particularly feasible, sensible, and devoid of MDD therapeutic stigmas. [NPID: Major Depressive Disorder, MDD, microbiome, microbiota-gut-brain axis, MGB, probiotics]

Human gut microbiome influences the central nervous system (CNS) by the microbiota-gut-brain axis. Therapeutic interventions that modulate the gut microbiota, like probiotics, may be helpful for mental health. In this systematic review and meta-analysis by De Sequeira et al. (2022), the authors present the available scientific evidence on the impact of probiotics on psychological well-being, symptoms of psychiatric disorders and CNS function. Conducting a search on several databases (PubMed, Web of Science and the Cochrane Library), the authors identified 54 randomized placebo-controlled studies (of which, 30 underwent meta-analysis). Current evidence demonstrates no quantitative relationships between probiotics and mood, stress, anxiety, depression, or psychiatric distress. From a qualitative standpoint, however, probiotics showed a modest improvement of depression and psychiatric distress. The authors thus conclude that the current state of evidence is promising, yet remains unclear as to how influential probiotics are and the domains of their efficacy in terms of improving psychiatric conditions and CNS functionality. [NPID: Anxiety, central nervous system (CNS), depression, meta-analysis, mood, paraprobiotics, probiotics, psychiatric distress, stress, systematic review]

The aim of this 2022 study was to examine the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress during public speaking. The healthy student participants were randomized to consume either L. rhamnosus-containing (the probiotic) or acidified (placebo) milk twice daily for 4 weeks. Small intestinal permeability was determined by the lactulose–mannitol ratio in the urine, as well as fractional excretion of lactulose (FEL) and mannitol (FEM). The students were also assessed on anxiety levels (through the State-Trait Anxiety Inventory) and perceived stress (through the Perceived Stress scores). There were no significant differences in urinary lactulose–mannitol ratio or lactose and mannitol excretion between the groups. But the increase in anxiety observed after the stress exposure was significantly lower in the test group than in the placebo group. According to the perceived stress score, those taking the probiotics seemed to show a preventative effect of Lactobacillus. This impact was more apparent in subjects with high stress-induced cortisol. With regards to safety of the probiotic, there were no adverse effects reported. In conclusion, L. rhamnosus CNCM I-3690 was found to prevent stress-induced hyperpermeability to mannitol. Some subjective stress markers were reduced with L. rhamnosus, compared with the placebo, suggesting that this probiotic can also reduce anxiety. [NPID: Lactobacillus, probiotic, anxiety, perceived stress, gut permeability, gut-brain interaction]

Since there has been increasing evidence indicating that the microbiota-gut-brain axis plays an influential role in health and disease, this 2017 study investigated whether chronic prebiotic treatment modifies behavior related to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered with fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), or a combination of both for the 3 weeks leading up to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. As well as this, the mice were examined on behavior and immunity upon exposure to chronic psychosocial stress. Chronic prebiotic treatments demonstrated antidepressant and anxiolytic effects. The administration of GOS, and the FOS+GOS combination reduced stress-induced corticosterone release. The prebiotics also modified specific gene expression in the hippocampus and hypothalamus and altered short-chain fatty acid concentrations in a manner that strongly suggests the therapy positively affects behavior. The combination of FOS and GOS attenuated the effect of chronic stress on corticosterone and proinflammatory cytokine levels, reduced depression-like and anxiety-like behavior, and normalized the impact of stress on the microbiota. Considering all this data, prebiotic treatments may improve stress-related behaviors. [NPID: diet, probiotics, gut microbiota, stress, microbiota-gut-brain axis, fructo-oligosaccharides, galacto-oligosaccharides]

This 2021 study examined the effect of taking galacto-oligosaccharides (GOS) daily for 4 weeks on nutrient intake and the gut microbiota. Recent research has shown the potential impact of prebiotics on general well-being and behaviors. Thus, young female adults were randomized to either receive GOS daily or a placebo for 4 weeks. Food diaries and stool samples were collected before and 28 days after the treatment. The GOS supplementation appeared to affect macronutrient intake. Intakes of carbohydrates, sugars, and fats were lower post-treatment. The greater abundances of Bifidobacterium in the GOS group, compared to the placebo group, predicted the reduction in carbohydrate consumption. This suggests that increased abundances of Bifidobacterium may help the gut microbiota composition by changing the individual’s desire to eat specific types of carbohydrates. [NPID: gut microbiota, prebiotics, probiotics, Bifidobacterium, galacto-oligosaccharides, nutrients]

This 2021 study tested the efficacy and safety of the probiotic NVP-1704 (a bacterial mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98) in improving health-related outcomes such as stress, depression, anxiety, sleep disturbances, and the levels of various blood biomarkers in the blood. The 156 participants were healthy adults with subclinical depression, anxiety, or insomnia. They were randomly chosen to either consume NVP-1704 or placebo for a period of 8 weeks. Assessments took place at baseline, and after 4 and 8 weeks of treatment. The composition of each subject’s gut microbiota was also examined at the end of the intervention through DNA sequencing. When compared with placebo, the group that received the bacterial mixture NVP-1704 demonstrated considerably fewer depressive symptoms at the 4- and 8-week mark, and fewer signs of anxiety at 4 weeks. Moreover, this treatment group reported better sleep quality than the placebo group. There was also a reduction in the blood concentration of interleukin-6 in the NVP-1704 group. Furthermore, consuming this probiotic resulted in increased Bifidobacteriaceae and Lactobacillaceae and decreased Enterobacteriaceae populations in the gut. The results suggest that the probiotic NVP-1704 promotes better mental health and sleep. [NPID: probiotics, bacteria, gut, microbiota, microbes, supplements, sleep, mental health, stress, depression, anxiety, insomnia]

This 2019 paper outlines the promise of probiotic use in the treatment of schizophrenia. The supporting clinical studies, as well as the pathways involved, availability in the Indian market, and relevant regulatory issues, are all discussed. Firstly described was the gut-brain communication pathway that is thought to be modulated by immune function and neurotransmitter concentration. Researchers ought to investigate how these modulations lead to the cognitive changes and improvement of schizophrenic symptoms. The results of some germ-free mice experiments particularly backed up this gut-brain relationship, since the antibiotic usage, which depleted the gut of bacteria, was associated with psychiatric side effects. While clinical trials confirming the safety and efficacy of probiotics in schizophrenia are ongoing, Grover et al. suggest other key areas of research to be studied such as gut microorganism transplants and the pharmacovigilance of probiotics. Another potential prospect is analyzing the effects of different diet types on the genetic make-up of the bacteria, neurotransmitters production capacity, and the psyche of the human host. This paper also discusses factors to take into account from a manufacturing standpoint such as the shelf life of probiotics, the stability of probiotics in the gut milieu, in the presence of food, secretions, and the exact volume needed for a particular age group. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, affect, cognition, depression, mania]

This 2019 double-blind, randomized, placebo-controlled study documented the affective and cognitive functions and biochemical parameters of 79 participants with major depressive disorder (MDD) to analyze the psychobiotic and immunomodulatory impact of the probiotic bacteria Lactobacillus Plantarum 299v (LP299v). Forty subjects were randomly selected to take a combination of SSRI antidepressant and the probiotic for 8 weeks, while the remaining 39 individuals were given the SSRI plus a placebo for the same length of time. The study only included data from the thirty people from each intervention group who completed the 8-week intervention for the analysis. In the LP299v group, there was a greater improvement in the Attention and Perceptivity Test (APT) and the California Verbal Learning Test (CVLT) total recall of trials 1-5 between pre- and post- intervention, compared with that of the placebo group. Biochemical analyses revealed significantly lower concentrations of kynurenine (KYN), and significantly increased 3-hydroxykynurenine: kynurenine ratio in the LP299v group relative to the placebo group. Moreover, a significant effect of interaction of Treatment x time was observed for anthranilic acid (AA) concentration. But there was no statistical significance found by post hoc analysis in neither probiotic nor placebo groups, and no significant changes of TNF-α, IL-6 and IL-1b and cortisol concentrations detected in either group. Rudzki et al. (2019) presented the first piece of evidence of cognitive functions improving and also KYN concentrations decreasing in MDD patients treated with probiotic bacteria. It was suggested that the lower KYN levels may have contributed to the enhanced cognitive results observed in the LP299v group compared to the placebo group. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, affect, cognition, depression, MDD, major depressive disorder, Lactobacillus Plantarum, SSRIs, SSRI]

The aim of this 2018 systematic review and meta-analysis was to determine the influence of probiotic supplementation on anxiety using clinical and preclinical data found on scientific databases (PubMed, PsycINFO, and Web of Science). The search results produced 22 preclinical studies (743 animals) and 14 clinical studies (1527 individuals) that met the inclusion criteria. Anxiety-like behavior was reduced by probiotics in animals, although the reduction was significant among diseased animals only, subgroup analyses revealed. Furthermore, the only species with anxiolytic ability was Lactobacillus (L.) rhamnosus, observed in the probiotic species-level analyses, which were later discovered to be broadly under-powered. Whereas, in human studies probiotics did not alleviate anxiety significantly, with similar measures for both healthy and clinical subjects. Although the anxiolytic qualities of probiotics were demonstrated in some preclinical studies, these findings have not been translated to clinical research, thus future research must explore the use of probiotics in anxiety further, especially considering the promising probiotic species L. rhamnosus. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, anxiety, animal, L. rhamnosus]

The effect of probiotic intake on psychological symptoms was explored by Mckean et al. (2017) through the systematically reviewing of randomized, placebo-controlled studies measuring depression, anxiety, and perceived stress in healthy volunteers before and after a probiotic intervention, and meta-analyzing those matching the inclusion criteria. The 7 included studies, which passed the quality assessment (using the Rosendal scale), provided adequate data for nine comparisons to be made. The meta-analysis showed that improvements seen in psychological symptoms of the probiotic-supplemented group were larger (standardized mean difference 0.34), and statistically significant, compared with placebo. These results portray the positive changes in psychological symptoms of depression, anxiety, and perceived stress that were induced by probiotic supplementation in healthy human volunteers. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, probiotics, depression, anxiety, stress]

In this triple-blind, placebo-controlled, randomized controlled trial published in 2015, 20 healthy participants without current mood disorder were administered with a multispecies probiotic [containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58)] for 4 weeks, while another 20 subjects received a placebo for the same length of time. Before and after the intervention, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. The aim was to examine the multispecies probiotic’s ability to reduce cognitive reactivity in a non-depressed population. The results indicated significantly reduced overall reactivity to sad mood in the probiotic-receiving group, largely taking into account the fewer aggressive thoughts and instances of rumination reported. Since it appears that the negative thoughts associated with sad mood were reduced after consuming probiotics for 4 weeks, probiotic supplementation could be a revelation as a preventer of depression and thus warrants further exploration. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, spatial memory, pro-inflammatory cytokines, neurodegeneration, depression, rumination]

This 2019 mouse-model study examined the impact of consuming multistrain probiotics for 21 days on hippocampal damage, spatial and learning memory of mice with cerebral hypoperfusion and assessed the possible mechanisms behind these effects. Several probiotic cocktails of bacteria were administered orally to the mice at concentrations of 10^7, 10^8 and 10^9 CFU/day for 3 weeks, before cerebral hypoperfusion was established in the mice by bilateral common carotid artery occlusion (BCCAO) for 20 min and 24 h reperfusion. Rahmati et al. (2019) also measured malondialdehyde (MDA) content and brain-derived neurotrophic factor (BDNF) level (using the ELISA technique), in addition to histological damage and apoptosis in the CA1, CA3 and dentate gyrus (DG) of the hippocampus 24 hours after ischaemia. All 3 concentrations of probiotic treatments substantially reduced the number of neuronal deaths and apoptotic cells in the CA1, CA3 and DG of the hippocampus. But none of the probiotics affected the BDNF and MDA levels in the hippocampus. At 10^9 CFU/day of probiotic supplementation, the spatial memory impairment and neurological dysfunction of the mice significantly improved. The data suggested daily consumption of the various bacteria strains in probiotics lessened the hippocampus damage and prevented learning and memory decline by stopping apoptosis in the mouse model with cerebral hypoperfusion. Probiotics may be a promising prophylactic for people susceptible to cerebrovascular diseases. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, hippocampus, BDNF, brain-derived neurotrophic factor, animal, spatial memory]

With the aim of uncovering the effect of microbiota in the gut, through probiotics intervention, on mental health like anxiety and its related factors, this 2019 double-blind, randomization-control study randomly assigned 86 healthy college students (average age 20.6, 75.6% female) to one of five conditions, including 4 probiotic treatments and one placebo, and provided these subjects with surveys before and after the 28-day probiotic/placebo intervention. These surveys revealed improvements in panic anxiety, neurophysiological anxiety, negative affect, worry, and regulation of negative mood among the groups who received probiotics. Rather than species counts, the number of significant developments seen were better attributed to the CFU (colony-forming unit) level. Furthermore, a ceiling effect was detected, with participants with high distress reporting more progress than those with normal degree of distress. As well as being the first study to analyze the impacts of CFU and species count on probiotics' efficacy, this trial finds that there is therapeutic potential in probiotics in the management of anxiety and encourages future studies to explore further. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, anxiety]

In this 2020 animal study, 62 Long–Evans rats were given Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 for life, along with the Western diet to determine the probiotic’s influence on anxiety, inflammation, and metabolic measures later in life. The formulation changed the rats’ anxiety-like behaviours in adulthood and affected their metabolic profile in various ways depending on sex. After probiotic treatment, calorie intake and leptin levels were increased and body weight was maintained in the female rats, while the nutraceutical supplement appeared to reduce the weight-gaining and calorie-consuming nature of the Western diet, while unaltering leptin levels in the males. The study observed the greatest inflammatory responses in male, Western-diet-exposed, and probiotic-treated rats, which implicate the relevance of steroid hormones. To summarize, the probiotic supplementation with Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 early in life may influence health at adulthood in a sex-dependent manner, although the health outcomes in both sexes may need to be investigated further in future studies. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, anxiety, inflammation, anxiety, leptin, Bifidobacterium longum, Lactobacillus helveticus]

The aims of this 2018 review were to analyze the evidence for the anti-inflammatory influence of probiotics, and to describe the potential mechanisms behind probiotics’ antidepressant effects on patients with major depressive disorders (MDDs), with a particular focus on modulation of the immune system. Park et al. (2018) provide us with a narrative review of studies exploring probiotics’ potential effects on systemic inflammation, obtaining the studies from PubMed/Medline, Google Scholar, and clinicaltrials.gov. The research thus far has suggested that probiotics can reduce the inflammatory activation commonly found in MDD and show promising results as part of adjuvant therapy. Admittedly, the research is still limiting currently, and would need to address several factors such as the roles of the blood-brain-barrier permeability, leaky gut and stress exposure, but nevertheless, depressed individuals appear to benefit from probiotics. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, inflammation, anti-inflammatory, immunity, systemic inflammation, adjuvant therapy, blood brain barrier, leaky gut]

Soldi et al. (2018) tested a probiotic product called Lactoflorene® Plus on healthy adult volunteers who had self-reported psychological stress, to examine its ability to prevent alterations in the immune response that are associated with stress and microbiota composition. The composition of the participants’ gut microbiota were analyzed, as well as their immunological parameters (sIgA, NK cell activity, IL-8, IL-10, TNF-α) in feces and salivary stress markers (α-amylase, cortisol, chromogranin A). The trial did not notice any direct effects of the probiotic product on the salivary stress markers nor NK cell activity, but abdominal pain was reduced and faecal IgA and IL-10 levels were elevated. The induction of moderate increases in Bifidobacterium and Lactobacillus spp were expected while the Faecalibacterium spp. population multiplied, and the Dialister spp. and Escherichia and Shigella communities shrunk. Lactoflorene® Plus was found to reduce intestinal inflammation and abdominal discomfort by protecting the mucosal barrier, achieved through promoting short-chain fatty acid production and reducing potentially harmful bacteria numbers. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, Bifidobacterium, Lactobacillus, inflammation, short-chain fatty acids, fatty acids]

This 2019 narrative review analyzed systematic reviews that assessed randomized controlled trials exploring the efficacy of probiotics as treatments for depressive symptoms. Here, Nadeem et al. (2019) discuss important biological mechanisms, and overview the history of probiotic use, allowing us to understand the impact of modern-day diet on mental health. Out of the 7 systematic reviews included from the 5-database search, 3 conducted meta-analyses, including 2 that found probiotic use led to improvements in depressive symptoms. Moreover, three out of the four reviews that performed qualitative analysis recognized the potential in probiotics as treatments for depression. The effect of probiotics on depressive symptoms can not be definitively concluded yet due to heterogeneity of the clinical trials but probiotics’ therapeutic potential in treating pre-existing depressive symptoms is clear. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, MDD, depression]

Liu et al. (2019) conducted a random-effects meta-analysis of 34 controlled clinical trials examining the effects of prebiotics and probiotics on depression and anxiety. The trial did not observe any difference in measures of depression between the prebiotic and placebo groups, although there was evidence of probiotics eliciting a small but significant impact in terms of depression and anxiety. The relationship between probiotics and depression was moderated by sample type: clinical/medical samples produced a larger effect than community samples; while in a preliminary analysis a medium-to-large effect was seen for psychiatric samples. Probiotics may possess antidepressant and anxiolytic qualities but the pooled effects were reduced here by the limited number of trials with clinical samples. Trials with psychiatric samples are encouraged to fully understand probiotics’ therapeutic potential. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, major depressive disorder, MDD, prebiotics, depression, anxiety]

Akkasheh et al. (2016) designed this randomized, double-blind, placebo-controlled clinical trial involving 40 patients [aged 20-55, diagnosed with major depressive disorder (MDD) based on DSM-IV criteria] and randomly allocating them into 2 groups to receive either probiotics supplements or placebo (split on a 50:50 basis) for 8 weeks. The aim was to test what impact the consumption of probiotics have on symptoms of depression and metabolic status in people with MDD. The probiotic capsule given contained three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) CFU/g), Lactobacillus casei (2 × 10(9) CFU/g), and Bifidobacterium bifidum (2 × 10(9) CFU/g). The participants’ dietary intake, which was determined by the dietary records reported by each individual, was not significantly different between the two groups. However, after 8 weeks of administering probiotics the subjects showed significantly lower Beck Depression Inventory total scores, compared to those in the control group. Significant drops in serum insulin levels were observed also, as well as homeostasis model assessment of insulin resistance, serum hs-CRP concentrations, while total glutathione concentrations in the blood substantially increased in the probiotic group. No marked changes in fasting blood glucose, homeostatic model assessment of beta cell function, quantitative insulin sensitivity check index, lipid profiles, nor total antioxidant capacity levels were reported. Nevertheless, patients with MDD given probiotics for 8 weeks experienced positive effects with respect to insulin levels, Beck Depression Inventory, homeostasis model assessment of insulin resistance, hs-CRP concentrations, and glutathione concentrations. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, major depressive disorder, MDD, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, depression, insulin, glutathione]

Karakula-Juchnowicz et. al (2019) planned this 12-week, randomised, double-blind and placebo-controlled study (SANGUT) to evaluate 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 and in order to determine the impact of interventions focused on the gut-brain-microbiota axis - which is backed by evidence to be a promising approach - in a group of MDD patients. A total of 120 outpatients will be equally assigned into one of four groups: probiotic supplementation plus gluten-free diet group (PRO-GFD); placebo supplementation and gluten-free diet group (PLA-GFD); probiotic supplementation and gluten containing diet group (PRO-GD); or placebo supplementation with 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 idea behind this study is that microbiota and its metabolites have the potential to influence CNS function and probiotics may restore the eubiosis (homeostasis) within the gut while a gluten-free diet may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. With the suggestion that microbiota may also be digest the gluten and play a role in the formation of peptides with different immunogenic capacities, the combination of the gluten-free diet with probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, depression, prebiotics, major depressive disorder, MDD, gluten, inflammation]