Table 2.
Clinical trials developed regarding probiotics administration and brain-related disorders.
| Disease/Disorder | Study Title/Acronym | Administered Probiotic Strain Type | Observations | Government Identifier | Citation |
|---|---|---|---|---|---|
| Stress Anxiety Insomnia Depression |
Psychiatric Symptoms in Employees Experiencing High Levels of Stress Before and After the Intake of Probiotics | (1) Lactobacillus plantarum: 10 billion CFU (colony forming units) (2) Lactobacillus paracasei: 10 billion CFU (3) The heat-treated Lactobacillus paracasei: 10 billion cells |
Perceived stress, anxiety, and the improvement of related biological markers | NCT04452253 | [215,216] |
| Emotional Stress | Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects | Lactobacillus helveticus, Bifidobacterium longum, and Lactiplantibacillus plantarum in addition to other nutrients: 3 billion CFU per 3 g powder sachet | Improvement of brain function and emotional regulation | NCT03615651 | [217] |
| Cognitive disorders Dementia | Probiotic on Psychological and Cognitive Effects | Lactobacillus Rhamnosus GG (L.GG) | L.GG did not lead to acute cognitive improvements for older adults already meeting physical activity guidelines | NCT03080818 | [218] |
| Autism Spectrum Disorder | Probiotics and Oxytocin Nasal Spray on Social Behaviours of Autism Spectrum Disorder (ASD) Children | Lactobacillus plantarum: 200 million CFU per day | Social behavior improvement | NCT03337035 | [219,220] |
| Cognitive Decline | The Cognitive Effects of 6 Weeks Administration With a Probiotic | Lactobacillus paracasei Lpc-37 | Improvement of the cognitive and mood effects | NCT03601559 | Not provided |
| Stress-related intestinal hyperpermeability | PRObiotic and Stress-related PERmeability (ProSPer) | A fresh fermented dairy drink containing L. rhamnosus CNCM I-3690 probiotic strain | L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol | NCT03408691 | [221,222] |
| Mood Disorders Depression | Probiotics Therapy of Mood Disorders | Probiotic Ecologic®Barrier (Winclove Probiotics BV) | Mood improvement and the reduction of depressive symptoms in females in the perimenopausal age group | NCT04753944 | Not provided |
| Epilepsy Stress Related Disorders | The Effect of Probiotic Supplementation in Drug-resistant Epilepsy Patients | Streptococcus thermophilus, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, Bifidobacterium breve, B. longus, B. infantis | Probiotic strains can alleviate stress-related disorders such as anxiety and depression | NCT03403907 | [223,224] |
| Mood Disorders | Investigating a Probiotic on Mothers’ Mood and Stress (Promote) | Bifidobacterium longum (BL) NCC3001 | Modulation of perinatal mood and stress during the perinatal period | NCT04685252 | Not provided |
| Cognitive Impairment | Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment | 109 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum | Cognitive change in Alzheimer’s Disease Assessment Scale-Cognitive-Plus (“ADAS-Cog-Plus”). | NCT05029765 | Not provided |
| Major Depressive Disorder | Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics (PROMEX) | Multi-strain probiotic containing 14 strains | Alleviation of depressive symptoms in patients with Major Depressive Disorder (MDD) | NCT03893162 | Not provided |
| Mild Traumatic Brain InjuryPost Traumatic Stress Disorder | Biological Signatures, Probiotic Among Those With mTBI and PTSD | Lactobacillus reuteri (L. reuteri; DSM 17938) | L. reuteri DSM 17938 exerted anti-inflammatory/immunoregulatory activity | NCT02723344 | [225] |
| Depressive Symptoms Anxiety Stress |
Probiotics, Brain Structure and Psychological Variables (ProBrain01) | Dietary Supplement: Vivomixx® containing 8 probiotic strains | Clostridium butyricum regulates the gut microbiota and restores the butyrate content in the feces and the brains. L. plantarum PS128 daily intake improves anxiety-like behaviors and ameliorates neuropsychiatric disorders. Probiotic administration exerts positive results on all measures of depressive symptoms. | NCT03478527 | [226,227,228,229,230,231,232,233] |
| Psychological Stress | Study on the Effects of a Probiotic on Autonomic and Psychological Stress | Lactobacillus helveticus R0052 and Bifidobacterium longum subsp. longum R0175 | Stress alleviation, cortisol level reduction, positive effects on brain activity | NCT02417454 | [234,235] |
| Severe Depression | Probiotic Supplementation in Severe Depression | Dietary Supplement: Vivomixx® containing 8 probiotic strains | The increase of the Lactobacillus was associated with decreased depressive symptoms. Probiotic administration ameliorates depressive symptoms together with changes in the gut microbiota and brain. | NCT02957591 | [236] |
| Acute Stress | Not specified: capsule containing freeze dried probiotic | NCT03284905 | Not provided | ||
| Depression Sleep Disorders Stress Anxiety Mood Disorders |
Probiotic Administration on Mood (PAM) | Lactobacillus fermentum, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium longum | Alleviation of the symptoms related to depression, anxiety, stress, insomnia, and emotional responses in healthy males and women. | NCT05343533 | Not provided |
| Bipolar Disorder Schizoaffective Disorder |
Probiotics to Prevent Relapse After Hospitalization for Mania | 108 CFU of the Lactobacillus GG and Bifidobacterium lactis strain Bb12. | Probiotic administration reduced the psychiatric rehospitalizations | NCT01731171 | [237] |
| Impulsive Behaviour Compulsive Disorder, ADHD Borderline Personality Disorder | Treating Impulsivity in Adults With Probiotics (PROBIA) | Pediococcus pentosaceus 5–33:3, Lactobacillus paracasei subsp paracasei 19, and Lactobacillus plantarum 2362 in combination with four fermentable fibres | Ameliorating the impulsivity, compulsivity, and aggression in adults with psychiatric disorders | NCT03495375 | [238] |
| Depression | Effect of Probiotic on Depression | Lactobacillus paracasei, Bifidobacterium animalis, Bifidobacterium longum, Bifidobacterium bifidum and Lactobacillus plantarum | Gut microbiota regulation and potential in alleviating depression | NCT04567147 | [232,239,240,241] |
| Autism Spectrum Disorders, Anxiety | Probiotics for Quality of Life in Autism Spectrum Disorders | “Visbiome Extra Strength”-a mix of 8 strains of beneficial bacteria (mainly Bifidobacteria and Lactobacilli) | Probiotic administration improves GI and pain symptoms, also reducing anxiety and ASD-related behaviors | NCT02903030 | Not provided |
| Schizophrenia Schizoaffective Disorder | Double-Blind Trial of a Probiotic Supplement to Reduce the Symptoms of Schizophrenia | Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis (BB12) | Probiotic administration caused a beneficial change in Positive and Negative Syndrome Scale after probiotic administration and positive effect on GI tract | NCT01242371 | [242] |
| Depression Anxiety | Effects of Probiotics on Mood |
Lactobacillus fermentum, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium longum |
Probiotic mixture as an adjuvant therapy for depression and anxiety. Probiotics administration has positive effects on depressive feelings. | NCT03539263 | [243] |
| Anxiety | The Probiotic Study: Using Bacteria to Calm Your Mind | Lactobacillus rhamnosus | Anxiety and abdominal pain reduction after probiotic administration. | NCT02711800 | [244] |
| Epilepsy | Probiotic in Treatment of Adult Patients With Drug-resistant Epilepsy | Combination of Lactobacillus and Bifidobacterium species | Not provided | NCT05160350 | Not provided |
| Social Stress | Effect of Probiotics on Central Nervous System Functions in Humans | Bifidobacterium longum 1714 | Probiotics can improve the response to social stress in healthy participants and patients with irritable bowel syndrome (IBS) | NCT02793193 | [245] |
| Physiological Stress, Cognitive Decline | Effects of Probiotics on Cognition and Health (EPOCH) | Fermented milk (probiotic) | Fermented dairy consumption increased the presence of certain microorganisms in the gut and improved relational memory in healthy adults. | NCT02849275 | [246] |
| Parkinson’s Disease | Trial of Probiotics for Constipation in Parkinson’s Disease |
Lactobacillus acidophilus, L. reuteri, L. gasseri, L. rhamnosus, Bifidobacterium bifidum, B. longum, Enterococcus faecalis, Enterococcus faecium |
Multi-strain probiotics treatment was effective for constipation in PD. | NCT03377322 | [247] |
| Mental Fatigue Cognitive Function Mood Disorders | Examining the Effects of One-Month Probiotic Treatment on Mental Fatigue | A novel probiotic formulation (not specified) | Anti-fatigue effects of a probiotic supplement after a period of cognitive demand. | NCT03611478 | Not provided |
| Autism Spectrum Disorder | Gut to Brain Interaction in Autism. Role of Probiotics on Clinical, Biochemical and Neurophysiological Parameters | Dietary Supplement: Vivomixx® | Vivomixx administration influenced inflammatory and gastrointestinal (GI) biomarkers, disturbances, behavioural and developmental profiles, and neurophysiological features in ASD pre-schoolers. | NCT02708901 | [248,249,250] |
| Major Depressive Disorder Depression Depressive Symptoms | The Efficacy, Safety, and Tolerability of Probiotics on the Mood and Cognition of Depressed Patients | Lactobacillus helveticus and Bifidobacterium longum | Positive changes in mood, anxiety, cognition, and sleep after probiotic administration. | NCT0283804 | Not provided |
| Psychological stress | A Study to Assess the Safety and Efficacy of Probiotic to Modulate Psychological Stress | Probiotic (not specified) | Probiotics can modulate the psychological stress experienced by healthy medical, dental and health science students. | NCT04125810 | Not provided |
| Psychological Stress | Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects | Lacticaseibacillus paracasei Lpc-37 at 1.75 × 1010 CFU per day | Probiotic administration can modulate stress and anxiety experienced by healthy subjects during and after an acute stressor compared to placebo. | NCT03494725 | [251] |
| Anxiety Stress | Evaluation of a Probiotic On Anxiety and Stress in Healthy Adults Sensible to Daily Stress (BIOSTRESS) | PROBIOSTICK® | Probiotic administration decreases stress and anxiety of people sensible to daily stress. | NCT00807157 | Not provided |
| Sleep Disorders | Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia (Prosit) | Fortified milk with Bifidobacteria infant-type and/or Lactobacilli | Functional milk administration improved sleep efficiency. | NCT03985228 | Not provided |
| Autism Spectrum Disorder | Efficacy of Vivomixx on Behaviour and Gut Function in Autism Spectrum Disorder (VIVO-ASD) |
Dietary Supplement: Vivomixx | Three-month supplementation with the Vivomixx improved overall function, aberrant behaviours, and the frequency of gastrointestinal symptoms in children with Autism Spectrum Disorders and co-morbid gastrointestinal symptoms. | NCT03369431 | Not provided |
| Depression Anxiety Disorder | Effect of Lactobacillus Plantarum 299v Supplementation on Major Depression Treatment | Lactobacillus Plantarum 299V | Lactobacillus Plantarum administration improved the patient’s general health condition during antidepressant monotherapy with SSRI (Selective Serotonin Reuptake Inhibitor) in patients with major depression. | NCT02469545 | Not provided |
| Autism | Effect of Milk Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Children With Autism | Synbiotic containing Bifidobacterium infantis SC268, bovine colostrum and bovine oligosaccharides. | Synbiotic administration can promote a healthy bacterial environment in the intestines of children with autism spectrum disorders and gastrointestinal complaints. | NCT02086110 | Not provided |
| Subjective Sleep Quality Objective Sleep Quality | Effect of B. Longum 1714™ on Sleep Quality | 1 × 109 CFU Bifidobacterium longum 1714™ | Probiotic administration improved sleep quality | NCT04167475 | Not provided |
| Evaluation of efficacy of SAMEUP in subjects with depression symptoms: a randomized study (SAMEUP) | Combination Product: SAMEUp containing S-adenosylmethionine (SAMe) 200 mg and Lactobacillus plantarum HEAL9 1 × 109 CFU | Improvement in the overall depression symptomatology after synbiotic administration. | NCT03932474 | [252] |