Probiotics, Prebiotics and Mental Health

Growing older is associated with alterations in the gut microbiota and a reduction in mental capacity. Psychobiotics are microbiota-targeted treatments that can improve mental health and slow down the brain's aging process. In comparison to people who are neurologically healthy, Aljumaah et al. (2022) examined the gut microbiome composition and predicted microbial functional pathways of middle-aged and older adults who met the criteria for mild cognitive impairment (MCI), in addition to conducting a placebo-controlled, double-blind, randomized clinical trial to examine the effects of probiotic Lactobacillus rhamnosus GG (LGG). A total of 169 middle-aged (52–59 years) and older (60–75 years) community-dwelling adults were randomly assigned to probiotic and placebo groups for a three-month intervention. Samples were taken at baseline and after supplementation. Based on their cognitive condition, participants were subsequently separated into intact or impaired cognition groups. Prevotella ruminicola, Bacteroides thetaiotaomicron, and Bacteroides xylanisolvens were found to be taxa linked with MCI by microbiome study. Prevotella was found to be substantially more common in MCI participants than in cognitively intact subjects, according to differential abundance analysis at baseline. An increase in the MCI group's cognitive score was associated with a relative abundance decline of the genera Prevotella and Dehalobacterium in response to LGG administration. According to these results, the authors comment that some gut microbiota members are associated with middle-aged and older persons' cognitive function. Upon further confirmation, these taxa may be utilized as important early markers of MCI and may be stimulated by prebiotics, probiotics, and symbiotics to facilitate favorable brain aging outcomes. [NPID: Prebiotics, probiotics, microbiome, supplements, cognitive decline, aging]

Given that the gut microbiota may contribute to depressive illnesses, it is a desirable target for therapies. The microbiota and the severity of depression symptoms differ significantly between racial and ethnic groups. Therefore, knowledge of mechanisms linking microbiome to depression across ethnic groups is necessary for any treatment for depression that targets the microbiome. In this study by Bosch et al. (2022), the authors describe the gut microbiota and its relationships to depressive symptoms in 6 ethnic groups (African Surinamese, Dutch, South Asian Surinamese, Turkish, Ghanaian, and Moroccan; N = 3211) living in the same metropolitan area using data from the HELIUS cohort. Taking into consideration individual variations in demographics, behavior, and medical conditions, the authors noted that gut microbiome diversity - both between (β-diversity) and within (α-diversity) people - predicts the severity of the symptoms of depression. Notably, no ethnic group has a different set of relationships. 29%–18% of the ethnic disparities in depression symptoms were explained by β-diversity. Numerous families of bacteria house the genera linked to symptoms of depression, most notably, Ruminococcaceae, Lachnospiraceae, and Christensenellaceae. In conclusion, the authors comment that their findings demonstrate how the gut microbiota and depressed symptom levels are related and that this connection is consistent across ethnic groups. Furthermore, the results imply that ethnic variations in the intestinal microbiome may contribute to the corresponding variances in depression. [NPID: Depression, adults, ethnicity, Epidemiology, diet, behavior, microbiome]

Benton, Williams & Brown (2007) investigated if drinking a milk beverage containing probiotics or a placebo would affect mood and memory, as it has been discovered that bad mood correlates with frequent constipation. In their randomly-allocated, double-blind, placebo-controlled experiment, aside from three trips to the lab, the subjects (n = 124, mean age = 61.8 years) carried on with their regular lives within their communities. Participants received either a milk drink containing probiotics or a placebo every day for three weeks. Measurements of mood and cognitive function were done at baseline, 10, and 20 days following ingestion. The authors noted that participants who reported experiencing constipation less frequently had higher baseline mental clarity, self-assurance, and joy levels. Even while taking the probiotic did not typically alter mood, this seemed to be an expression of the sample's positive mood overall. Those in the bottom third of the baseline sad/elated dimension preferentially reported feeling happier instead of depressed after taking the probiotic. The fact that the intervention did not affect reported defecation frequency is likely due to the initially low prevalence of constipation. A surprising and maybe accidental finding was that probiotic use was associated with somewhat worse performance on two memory tests. The authors comment that participants who originally had a low mood found that their mood improved after consuming a probiotic-containing yogurt intervention. However, there was no correlation between this mood enhancement and a higher frequency of defecation. [NPID: Affect, cognition, constipation, defecation, probiotics, yogurt]

A probiotic formulation (PF) including Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) reduced gastrointestinal pain brought on by stress in prior clinical research. Probiotics taken orally may thus have positive effects on mood and psychological discomfort, according to emerging research linking the gut microbiota to central nervous system activities. Investigating PF's anxiolytic-like activity in rats and its potential effects on stress, anxiety, depression, and coping mechanisms in healthy human volunteers were the goals of this study by Messaoudi et al. (2011). In a preliminary investigation, rats were put to the test in the conditioned defensive burying test, a screening procedure for anti-anxiety drugs, after receiving PF daily for two weeks. The Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL), and 24-hour urinary free cortisol (UFC) were used in the clinical trial to assess volunteers' responses to PF administered for 30 days. In particular, the HSCL-90 scale (global severity index, somatization, depression, and anger-hostility), the HADS (HADS global score and HADS anxiety), the CCL (problem-solving), and the UFC level were used to measure the effects of daily subchronic PF administration on anxiety-like behavior in rats and psychological distress in volunteers. The authors noted that, when administered together, L. helveticus R0052 and B. longum R0175 exhibit anxiolytic-like action in rats and positive psychological effects in healthy human volunteers. [NPID: Psychological adaptation, adults, anxiety, Bifidobacterium, depression, Lactobacillus helveticus, probiotics, psychotropic drugs, rats, Somatoform disorders, stress]

Probiotics are a prominent instance of an innovative therapy for mood disorders that aims at the microbiota-gut-brain axis. More safety and effectiveness data are required to support this therapeutic strategy as there haven't been many clinical trials. Through this work by Nikolova et al. (2023), the authors sought to discover more information on probiotics' acceptability and tolerability and estimations of the intervention's effect size in patients with major depressive disorder (MDD). Adults with MDD who were taking antidepressants but had an insufficient response were examined in this single-center, double-blind, placebo-controlled pilot randomized clinical study. Participants received either an 8-week intervention of multistrain probiotic (8 billion CFU/day) or a placebo in addition to their regular antidepressant therapy. Retention, tolerability, acceptability, and estimates of treatment impact on clinical symptoms (depression: Hamilton Depression Rating Scale [HAMD-17] and Inventory of Depressive Symptomatology [IDS] scores; anxiety: Hamilton Anxiety Rating Scale [HAMA] and General Anxiety Disorder [GAD-7] scores) were the trial's pilot results, which were to be used as benchmarks for a more extensive study. Of the 50 individuals included, 49 took part in the intervention and were counted in the analyses with the intention of treating them. Of these 49, 39 (80%) were female, and the mean (SD) age was 31.7 (9.8) years. Twenty-four people were randomized to get probiotics, while 25 received placebos. Adherence was 97.2%, there were no significant negative side effects, and there was an 8% attrition rate (1 in the probiotic group and 3 in the placebo group). Analysis of the results revealed that, compared to the placebo group, the probiotic group saw higher reductions in anxiety symptoms as measured by HAMA scores and greater reductions in depressive symptoms as measured by HAMD-17 and IDS Self Report scores, but not GAD-7 scores. The authors recommend that probiotics be further researched as an adjunctive treatment for MDD patients in a conclusive efficacy study because of their acceptance, tolerability, and predicted impact sizes on important clinical outcomes. [NPID: Diet, probiotics, Major Depressive Disorder, adults, anxiety, adjunctive therapy]

Probiotics have been linked to the management of anxiety and depression, and have been used on individuals with a range of emotional states, but no meta-analysis has explicitly mentioned this. As a result, the findings that have been published in the literature have been uneven. In this meta-analysis by Chao et al. (2020), the authors looked at how well probiotics worked to treat nervous or depressive symptoms in people who were under stress or had been diagnosed with a depressive or anxiety illness. Through December 2019, Medline, PubMed, EMBASE, and the Cochrane Library were examined for randomized controlled studies (RCTs) that met the following criteria: Probiotic RCTs for individuals with a diagnosis of a mood disorder or mental illness or in stressful circumstances were the primary selection criteria, and all subjects had to be adults (minimum age16 years). Depression and anxiety ratings were the main results. Finally, three low-quality studies and seven high-quality studies were identified using the modified Jadad evaluation measure, culminating in the incorporation of ten clinical studies (n = 685 total participants). Analysis of the included studies revealed that probiotics can substantially lower the depression scale for patients with anxiety and depression as well as healthy individuals who are under stress, according to the meta-analysis. Even though the patients were stressed-out healthy volunteers or worried or depressive patients, there was no discernible difference between the probiotics and placebo groups in the decrease of patient anxiety ratings. Further subgroup analysis revealed that probiotics had a substantial impact on depressive symptoms only in patients with depression. However, there was no significant difference in patients' anxiety levels, and there was no gain in participant behavior under duress. The authors conclude that probiotics may be adjunct treatments for mood or emotional disorders because they have been shown to reduce depressive symptoms in patients with a diagnosis of depression or depression scores in an anxiety disorder diagnosis. The authors highlight that probiotics must therefore be used more frequently in the therapy of depressed people in the future. Probiotics are effective in treating depression, but more high-quality research on depressed individuals is still required. [NPID: Probiotics, depression, anxiety, under stress, meta-analysis]

Current evidence points to the positive impact of probiotics on improving mood and anxiety symptoms via influencing the gut-brain axis. However, the impact of probiotics on Major Depressive Disorder (MDD) patients who are not on treatment is unknown. In this open-label pilot study by Wallace & Milev (2021), the authors investigated the impact of probiotic supplements on 10 treatment-naïve MDD patients for a period of eight weeks, evaluating symptoms of depression before and after the probiotic intervention, with the aim to produce a volume of preliminary data in order to facilitate conducting a more prudent double-blind, randomized, placebo-controlled trial. The participants hailed from the same local community, and were given a probiotic supplement composed of Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 (3 × 109 CFU once/day for eight weeks - CEREBIOME®). Depression was evaluated using the CAN-BIND protocol of self-reported questionnaires and clinical scales. Data for the study was collected at three timepoints: initiation, fourth week and at completion (eighth week). Analysis of the data revealed that participants experienced a substantial amelioration of symptoms of depression by the fourth week, which carried forward to the eighth week. In particular, the participants experienced a substantial enhancement in sleep quality by the eighth week, with no reported adverse effects from using the probiotic supplement. The authors conclude that their study corroborates current findings on the impact of probiotics in improving depressive symptoms in treatment-naïve MDD patients, and that these supplements are safe for use. Finally, the authors comment that more research is necessary in order to develop treatment guidelines. [NPID: Probiotics, Major Depressive Disorder, pilot study]

In this randomized, double-blind, placebo-controlled study by Bagga et al. (2018), the authors examined the effect of introducing a probiotic supplement on the gut microbiome, cognitive and emotional behavior, and cerebral function, in a population of 45 healthy individuals (20 - 40 years old). The participants were divided into three groups (placebo, probiotic, no intervention) and had their emotional decision-making and emotional recognition memory evaluated for the duration of the intervention (four weeks) using functional magnetic resonance imaging (fMRI). In addition, the participants submitted self-reported questionnaires and stool samples to examine their gut microbiome. Analysis of the results revealed that probiotic supplementation leads to substantial enhancements in self-reported positive affect, cognitive reactivity, emotional memory, emotional decision-making, modulated brain activity, and shifted intestinal microbiome composition. The authors comment that their results provide novel evidence of the impact of probiotics on neural, behavioral, and microbiome aspects of the physiology of healthy adults, which presents the necessity of further research to investigate the contributions of the gut microbiota to health and the use of probiotic interventions for therapeutic gains. [NPID: Emotional decision, behavior, fMRI, microbiome, probiotics, recognition, memory, stool]

Stress has been demonstrated to affect human intestinal microbiota, causing mental health derangements like anxiety and depression. The functions of the gut microbiota include the synthesis and/or consumption of several neuroactive molecules, and several human studies demonstrated how probiotics can alter neurotransmitter levels by influencing the microbiome. However, several challenges stood in the face of understanding the biological importance of microbial neuroactive compounds, namely, the need for a reference database documenting their corresponding human intestinal microbiota reference genomes. In their previous studies, Ma et al. showed how consuming the probiotic strain Lactobacillus (L.) plantarum P-8 for 12 weeks improved stress and anxiety in adults. In this recent study (2020), the authors followed up on their previous work to understand the underlying mechanisms behind their results through the use of fecal metagenomic analysis of the probiotic (n = 43) and placebo (n = 36) groups. Analysis of the results demonstrated a substantial difference in gut microbiota between probiotic and placebo groups, with a significant decline of microbiome diversity observed in the placebo group compared to the probiotic group. Furthermore, the probiotic group demonstrated a substantial enhancement in the species-level genome bins (SGBs) of Bifidobacterium adolescent, Bifidobacterium longum, and Fecalibacterium prausnitzii, and reductions in Roseburia faeci and Fusicatenibacter saccharivorans. In addition, the 12-week probiotic supplement regimen increased the diversity of neurotransmitter-synthesizing and/or -consuming SGBs and their dependent levels of neuroactive molecules (namely, short-chain fatty acids, gamma-aminobutyric acid, arachidonic acid, and sphingomyelin). In conclusion, the authors highlight a possible mechanism explaining how probiotics alleviate stress and anxiety through the gut-brain axis, which may present a potential interventional avenue to address stress and anxiety. [NPID: Stress, anxiety, depression, gut microbiota, gut brain axis, neurotransmitter metabolites]

Prebiotic and probiotic gut microbiome-targeting therapeutic interventions are postulated to aid mental health. Despite being rich sources, fermented foods and others copious in prebiotics have not been evaluated for their efficacy. In this prospective cohort study by Karbownik et al. (2022), the authors investigate the impact of consuming fermented and prebiotic-rich foods on cognitive performance and symptoms of anxiety and depression in a population of otherwise healthy medical students suffering from psychological stressors. 372 participating students (aged 22.7 ± 1.1 years, 66% of which were females) reported on their food consumption through a 7-day dietary record, and on the symptoms of depression and anxiety they experienced using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Cognitive performance was evaluated based on academic examination performance. The results showed that fermented foods and food-derived prebiotics had no significant effect on cognitive performance under stress. However, a significant increase in symptoms of anxiety and depression was noted with an increasing intake of fermented foods, while food-derived prebiotics had no such impact. The authors thus conclude that fermented foods and food-acquired prebiotics do not affect cognitive performance under stress, though a higher consumption of fermented foods caused an increase in severity of anxiety and depressive symptoms. Further work is necessary to ascertain the safety profiles of fermented foods with respect to this psychologically vulnerable population. [NPID: Anxiety, cognitive function, depression, fermented food, prebiotics, probiotic, psychological stress]

This 2018 study focused on determining prebiotics’ potential effects on immunity and cognition because prebiotics affect the gut microbiota (a key regulator of neurological inflammation) and that the neuroinflammation induced by surgery is influential in postoperative cognitive dysfunction (POCD). The researchers therefore designed an experiment where adult rats undergoing abdominal surgery were fed with water or prebiotic Bimuno® (galactooligosaccharide (B-GOS) mixture) for 3 weeks. The aim of the research was to check if this prebiotic could ameliorate postoperative cognitive dysfunction and reduce surgery-induced neuroinflammation. Three days after surgery, the rats showed signs of impairment in novel objective recognition compared with rats in the control condition. There was also a notable increase in inflammatory markers in the hippocampus of these rats post-surgery, with elevated expression of activated microglia and increased levels of interleukins evident. But the administration of the prebiotic mixture B-GOS reduced cognitive decline significantly. Following treatment with B-GOS, activation of microglia and expressions of M1-related genes and interleukin-6 levels dropped considerably. There were still some microglial markers and interleukin-4 levels that did not differ significantly between the surgical and B-GOS groups. But the prebiotic treatment group was found to have experienced a significant change in diversity of the gut microbiome and proliferation of Bifidobacterium and other potentially anti-inflammatory microbes. This study concluded that administration of prebiotic B-GOS has a positive effect on neuroinflammatory and cognitive impairment in a rat model of abdominal surgery. [NPID: cognition, inflammation, surgery, prebiotic, supplement, gut microbiota, gut-brain axis, Bimuno, B-GOS, galactooligosaccharide]

In this 2021 study, healthy female adults were assessed on mood and well-being after taking galacto-oligosaccharides (GOS) prebiotic supplements every day for 4 weeks. Stool samples were collected before and after the intervention to analyze their gut microbiota. This study focused on nutritional supplementation in participants transitioning between late adolescence and early adulthood since these supplements have the potential to offset health-related costs in later life. The results suggested that galacto-oligosaccharide (GOS) prebiotics may improve indices of pre-clinical anxiety. This was postulated based on the effect of GOS on trait anxiety, attentional bias, and bacterial abundance. These findings will contribute greatly to gut microbiota research. Having said that, with the current interest in this research area coming from scientists and community alike, additional human studies are warranted. [NPID: gut microbiota, galacto-oligosaccharides, prebiotics, supplementation, supplements, anxiety]

This 2021 review evaluated randomized clinical trials that used probiotics or placebos in patients with major depressive disorder (MDD) and reported any psychometric score. The overall aim was to assess the effect of taking a new class of probiotics-psychobiotics on psychometric scales and the immune system. Medical databases were searched for relevant research articles from database inception until 22 April 2021, yielding ten eligible studies. The mean duration of the studies was around 49 days. The participants were mostly women and averaged 38 years of age. The results showed that probiotics may alleviate symptoms of major depressive disorder. The effectiveness of the probiotic treatment appeared to be related to time of administration. Psychobiotic therapy also tended to be more effective in men. To conclude, psychobiotics hold great potential in the treatment of major depressive disorder, although it is difficult to recommend a particular strain, dosage, or treatment duration. [NPID: probiotics, psychobiotics, gut microbiota, gut health, major depressive disorder, depression, review]

In this 2020 double-blind study, Saccarello et al. investigated the effect of SAMe (S-adenosylmethionine) 200 mg combined with Lactobacillus plantarum (L. plantarum) HEAL9 consumption for 6 weeks on symptomatology of mild-to-moderate depression. Ninety patients were randomized to either the probiotic group (SAMe plus L. plantarum HEAL9, n = 46) or placebo (n = 44) group. The Zung Self-Rating Depression Scale (Z-SDS), which indicates depression symptom severity, was reduced at the 6-week treatment mark in the probiotic combination group, compared to placebo. As well as the depression scale, treatment with probiotics was shown to significantly reduce cognitive and anxiety subdomains, and anxiety (in the questionnaire) at the 2-week stage, relative to the placebo condition. To conclude, the administration of SAMe and L. plantarum HEAL9 by adults with subthreshold or mild-to-moderate depressive symptoms showed clinical effects that were independent of symptom severity in 2 weeks. Aspects of depression, anxiety, and cognition were enhanced while the safety of these probiotics was also confirmed (no treatment-related adverse events). [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, depression, anxiety, cognition]

This 2018 trial explored the potential of probiotic organism consumption in the prevention of psychiatric rehospitalizations among 66 patients recently discharged for mania. The probiotic administered to the patients contained Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12. The subjects were randomly assigned to either receive the dose of probiotics or treatment with a placebo. Over the course of 24 weeks, 24 of the 33 individuals in the placebo group, and 8 of the 33 probiotic group participants, were readmitted to hospital. The probiotic administration was not only associated with a lower rehospitalization rate but also resulted in fewer days spent in the hospital by those readmitted (mean 8.3 vs 2.8 days for placebo and probiotic treatment). Results also demonstrated that probiotic treatment was more effective in individuals with higher levels of systemic inflammation at baseline. In conclusion, Dickerson et al. uncovered the lowering impact of probiotics on the rate of hospitalization among patients who have been recently discharged for mania. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, affect, cognition, depression, mania]

With promising preclinical data on the probiotic species Lactobacillus rhamnosus (JB-1), this 2017 randomized controlled trial examined the probiotic on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in a healthy human population. This was a 8-week long, randomized, placebo-controlled, cross-over trial involving 29 male volunteers. Cognitive assessments and resting electroencephalography (EEG) were taken, while participants also self-reported stress measures for this experiment. Subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT), and salivary cortisol was determined by ELISA. Other measures included plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release. The results showed no differences in mood, anxiety, stress or sleep quality between the groups, and no significant anti-inflammatory effects or great benefit in taking the probiotic over placebo in terms of subjective stress measures and HPA response to the SECPT. Moreover, no improvement was observed regarding visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures. The promising preclinical data could not be replicated in a human sample in this study, but interventional studies are encouraged to analyze this psychobiotic in people with stress-related disorders. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, inflammation, stress, cortisol, anxiety, sleep, sleep quality]

This 2020 systematic review scoured through the online databases Medline, PubMed, Scopus, Web of Science and clinical trials.gov with the aim of finding out whether probiotic supplementation can have a profound effect on psychological stress and anxiety disorders, and if so, to what extent. Vitellio et al. (2020) searched for double blind, randomized and placebo controlled or prospective studies, and those studies that also assessed psychological signs of perceived stress and anxiety pre- and post-intervention. The twelve studies that met the inclusion criteria, 3 of which were on stress, 4 on anxiety, and 5 on both stress and anxiety, made up a total of 1521 participants. Measures of stress improved in 1 out of the 3 studies, while 3 of the 4 studies measuring anxiety reported better outcomes, and 2/5 found positive results for both stress and anxiety. This article views probiotics as a potential enhancer of psychological symptoms given the evidence, especially regarding anxiety. Research should be continued to test probiotics on psychological stress disturbances. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, anxiety, stress]

Ng et al. (2018) conducted this meta-analysis on 10 clinical trials (with a total of 1349 patients) that analyzed the effect of probiotic supplementation on depressive symptoms, compared with placebo controls, which were published in English between 1-Jan-1960 and 1-June-2017 and found on one of these databases: PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), or Cochrane Field for Complementary Medicine. Although no significant difference in mood was identified between the treatment and placebo group post-intervention [standardized mean difference (SMD) = -0.128], another subgroup analysis of studies involving both healthy and depressed participants revealed that in those with mild to moderate depressive symptoms, mood was significantly enhanced (SMD -0.684, P=0.029) while the impact in healthy individuals was not significant (SMD -0.0999, P=0.146). Conducting this review, Ng et al. (2018) found it challenging to compare current clinical trials due to the inter-study discrepancies (probiotic dosing, bacterial strains and strain combinations) and the mostly healthy samples used in the randomized clinical trials made it difficult to extrapolate the results to depressed people. But overall, additional studies are desired, in particular on populations with clinically diagnosed depression. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, probiotics, depression, anxiety, neurosis]

Heyck & Ibarra (2019) discuss the significant connection between gut microbiota and brain function that has gained attention recently, highlighting the findings from one study that tested the effects of probiotic and prebiotic supplementation on the spatial and associative memory of middle-aged rats. Rats given both probiotic and prebiotic therapy exhibited significantly better spatial memory but not associative memory, compared with other groups. This greater performance in spatial memory tests was related with higher BDNF concentrations, lower levels of pro-inflammatory cytokines, and better electrophysiological readings in the hippocampus. These results therefore support that the rate of cognitive decline can be affected by probiotic- and prebiotic-induced alterations in microbiota. The data presented by this review can also be utilized to help tackle neurodegeneration and inflammation associated with aging and the posttraumatic impacts of ischemic stroke. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, prebiotics, spatial memory, pro-inflammatory cytokines, neurodegeneration, aging, stroke, inflammation]

This 2018 article considers the influencing role of probiotics in behavior and brain function, and promotes further investigation into the possible relations between the gastrointestinal tract and the CNS since preliminary human and animal studies had observed the anxiolytic effects on the CNS of several probiotic formulations containing Lactobacillus/Bifidobacterium. The early studies began implicating probiotics in the mechanisms behind the connection between the gut and the brain thought to modulate anxiety-like behaviors. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, brain function, Gastrointestinal tract, digestion, Lactobacillus, Bifidobacterium, anxiety]

In this 2016 systematic review, the databases Medline, PsycINFO, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (published between January 1990 and January 2016) that investigated the effect of probiotic supplementation on depression and anxiety symptoms. Little support was found for the therapeutic use of probiotics in depression and anxiety from the ten trials included in this review (4 clinically diagnosed, 6 non-clinical). But the findings imply humans may benefit psychologically from these probiotics, despite the inconsistencies in methodologies between the included studies. Future studies are imperative now to add to the current knowledge on probiotics and its developmental, modulatory, and metagenomic impacts on the GI microbiota. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, depression, anxiety, GI microbiota]

As the role of probiotics on psychiatric comorbidities are not well known although its beneficial effects on irritable bowel syndrome (IBS) are well reported, this 2017 randomized, double-blind placebo-controlled trial analyzed the impact of the probiotic bacteria Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. The 44 participants of this trial were students at McMaster University in Canada and had IBS and diarrhoea or a mix of stool patterns (based on Rome III criteria), coupled with mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale). The students were assessed on clinical history and symptoms and their blood samples were taken, before being randomly allocated to either BL (n = 22) or placebo (n = 22) for 6 weeks. The organizers provided validated questionnaires at weeks 0, 6 and 10, to measure severity of anxiety and depression, IBS symptoms, and report their quality of life and stress/mood. In addition, stool, urine and blood samples were collected and a functional magnetic resonance imaging (fMRI) test was performed at weeks 0 and 6. The patients’ brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels were also monitored. The results showed that BL did not significantly modulate anxiety or IBS symptoms, but at week 6 reduced the depression scores of 14 out of 22 subjects by 2 points or more, compared to 7/22 patients in the placebo group. Moreover, depression scores at week 10 were lower in the BL group than placebo. BL also reduced responses to negative emotional stimuli in the amygdala and fronto-limbic regions of the brain (as indicated by the fMRI), and increased quality of life scores, to a greater degree than the placebo. The 2 groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but those given BL exhibited lower levels of methylamines and aromatic amino acids metabolites present in the urine. Pinto-Sanchez and her team (2017) have discovered the antidepressant effect of the probiotic BL, which can be associated with alterations in brain activation patterns, demonstrating the probiotics’ ability to reduce limbic reactivity. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, depression, anxiety, IBS, amygdala, fronto-limbic, inflammation, Bifidobacterium longum]

Since probiotics have been increasingly suggested to be capable of reducing stress and anxiety and alleviating mood, the purpose of this 2019 systematic review and meta-analysis was to present all published evidence on probiotics’ efficacy as a treatment for depression in clinically depressed individuals. Randomized controlled trials involving the use of probiotics as either supplementary or standalone treatment in depressive patients were considered eligible for this systematic review. Information on sample characteristics, treatment effectiveness, tolerability and risk of bias were then extracted from the eligible studies. Nikolova et al. (2019) gathered data on 229 patients, taken from the 3 studies that met the inclusion criteria - two of which provided probiotics as part of supplementary therapy and one as a standalone treatment for depression. When this standalone treatment study was removed from the meta-analysis due to clinical heterogeneity, this revealed probiotics’ positive impact on overall depressive symptoms (standardized mean difference = 1.371, 95% confidence interval 0.130-2.613). Although additional studies will be required, and the potential mechanisms explored, the results of this meta-analysis imply probiotics may have beneficial effects on depressive symptoms when given as adjuvant therapy with antidepressants. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, stress, prebiotics, anxiety, depression]

Since the gut microbiota was suggested to interact with brain-derived neurotrophic factor (BDNF), which has been associated with having antidepressant qualities in the past, this 2020 double-blind, randomized controlled trial aimed to elucidate the mechanism of action of a psychobiotic combination (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175; CEREBIOME) that has already significantly improved depressive symptoms in patients with depression. Heidarzadeh-Rad et al. (2020) conducted this exploratory post hoc analysis of BDNF levels using 78 from the 110 patients who took part in this trial (probiotic = 28, prebiotic = 25, placebo = 25). The serum BDNF levels at baseline were compared with the levels at endpoint, to find significant differences between the groups. Significant increases in BDNF concentrations were seen in the probiotics group compared to both the prebiotic (P < 0.001) and placebo groups (P = 0.021). The probiotic group was also associated with significantly lower depression severity compared with placebo (ANOVA/ANCOVA, P = 0.012; Pearson, r = -0.79, P < 0.001). BDNF levels were reduced in the prebiotic group but not significantly relative to placebo. It is possible that the fewer depressive symptoms observed in the patients treated for 8 weeks with B. longum and L. helveticus occurred due to the increase in BDNF levels. [NPID: probiotics, gut-brain axis, gut microbiota, gut bacteria, microbiota, gut microbiome, MDD, depression, prebiotics, BDNF, brain-derived neurotrophic factor]