Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Selection Criteria
2.3. Data Extraction
2.4. Data Analysis
3. Results
3.1. Database Searches
3.2. Studies Characteristics
3.3. Microorganism Strains
3.4. Assessment Tools for Anxiety and Depression
3.5. Treatment Duration
3.6. Clinical Outcomes
3.7. Maternal Health
3.8. Microbiota Diversity and Abundance
3.9. Inflammation Biomarkers
3.10. Changes in Metabolic Profile
4. Discussion
Limitations
5. Conclusions and Future Directions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Authors/Year | Type of Study | Assessment Tools for Anxiety/Depression | Findings and Comments | Probiotic Strains in the Supplement | Duration |
---|---|---|---|---|---|
Schaub et al., 2022 [45] | Randomized controlled trial | Hamilton Depression Rating Sale (HAM-D)—clinical assessment; Beck Depression Inventory (BDI)—self-report rating inventory; State–Trait Anxiety Inventory 1 (STAI)—self-report scale | Results show a stronger decrease in the HAM-D scores in the probiotics relative to the placebo group. The increase in the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. | Probiotic supplement (Isomax) containing eight different strains (Streptococcus thermophilus NCIMB 30438, Bifidobacterium breve NCIMB 30441, Bifidobacterium longum NCIMB 30,435 (Re-classified as B. lactis), Bifidobacterium infantis NCIMB 30,436 (Re-classified as B. lactis), Lactobacillus acidophilus NCIMB 30442, Lactobacillus plantarum NCIMB 30437, Lactobacillus paracasei NCIMB 30439, Lactobacillus delbrueckii subsp. Bulgaricus NCIMB 30,440 (Re-classified as L. helveticus) | 4 weeks add-on therapy |
Kazemi et al., 2019 [46] | Double-blind Randomized Controlled Trial | Beck Depression Inventory (BDI)—self-report rating inventory | Probiotic supplementation resulted in a significant decrease in BDI compared to controls and prebiotic groups. | Probiotic (Lactobacillus helveticus and Bifidobacterium longum), prebiotic (galactooligosaccharide) | 8 weeks |
Lee et al., 2021 [47] | Randomized, Double-Blind, Placebo-Controlled Trial | Stress Response Inventory (SRI), Beck’s Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index. All participants were asked to complete self-report questionnaires | The NVP-1704 group had a more significant reduction in depressive and anxiety symptoms, while also experiencing an improvement in sleep quality. | Probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 | 8 weeks |
Chahwan et al., 2019 [48] | Randomised, Triple-blind, Placebo-Controlled Trial | Beck Depression Inventory (BDI)—self-report rating inventory | Probiotics did not significantly alter the microbiota of depressed individuals; however, a significant correlation was found between Ruminococcus gnavus and one depression metric. | Probiotic powder mixture: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, L. acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58 | 8 weeks |
Rode et al., 2022 [49] | Randomized Controlled Trial | Hospital Anxiety and Depression Scale (HAD)—self-report rating scale | Psychological symptoms, such as depression and anxiety, trended towards improvement after probiotic intervention. | Probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus, and Lactiplantibacillus plantarum. | 4 weeks |
Pinto-Sanchez et al., 2017 [50] | Randomized, double-blind, placebo-controlled study | Rome III criteria—clinical assessment; Hospital Anxiety and Depression scale (HAD)—self-report rating scale | Patients in the Bifidobacterium longum(BL) group had reduction in depression Scores vs. patients in the placebo group. Bifidobacterium longum(BL) had no significant effect on anxiety. | Bifidobacterium longum NCC3001 (BL) | 6 weeks |
Yang et al., 2016 [51] | Randomized, placebo-controlled study | Hamilton Anxiety Rating Scale (HAMA)—clinical assessment | Taking probiotics relieved the degree of anxiety of the patients. After ingestion of probiotics, serum levels of CRF did not increase before surgery. | Clostridium butyricum, Kexin Biotech, Shangdong, China | 2 weeks |
Reininghaus et al., 2020 [52] | Randomized Controlled Trial | Hamilton Rating Scale of Depression (HAMD)—clinical assessment; Beck Depression Inventory (BDI-II)—self-report rating inventory; Symptom Checklist-90-Revised (SCL-90)—clinical assessment | Probiotic plus biotin supplementation, in patient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures. | Multistrain probiotic includes B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W22, L. casei W56, L. paracasei W20, L. plantarum W62, L. salivarius W24, and L. lactis W19 | 4 weeks |
Zhu et al., 2023 [53] | Randomized, placebo-controlled study | Chinese version of Athens Insomnia Scale (AIS-8)—self-reported; Chinese version of Hamilton Depression Rating Scale (HDRS-17)—clinical assessment; Chinese version of Hamilton Anxiety Rating Scale (HAMA-14)—clinical assessment | L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety and depression in test anxious college students. This effect could be related to the regulation of gut microbiota. | Lactobacillus plantarum JYLP-326 | 3 weeks |
Chen et al., 2021 [54] | Preliminary Open Trial | Hamilton Depression Rating Scale (HAMD-17)—clinical assessment; Depression and Somatic symptoms Scale (DSSS)—self-report questionnaire | After PS128 intervention, scores of depression symptoms significantly decreased. However, the composition of gut microbiota did not significantly change. | Lactobacillus plantarum PS128 | 8 weeks |
Tran et al., 2019 [55] | Double-Blind, Randomized Placebo-Controlled Trial | Beck anxiety inventory (BAI)—self-report rating inventory; Anxiety control questionnaire revised (ACQ-R)—clinical assessment; Positive and negative affect schedule (PANAS)—self-report questionnaire; Negative mood regulation (NMR)—self-reported; Penn state worry questionnaire (PSWQ)—self-reported | Probiotics were observed to improve panic anxiety, neurophysiological anxiety and increase negative mood regulation. In addition, participants with high distress reported higher number of improvements than those with normative distress. | Commercially available as over-the-counter products (varied) | 4 weeks |
Slykerman et al., 2017 [56] | Randomised Double-blind Placebo-controlled Trial | Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory—self-reported questionnaires | In the postpartum phase, women who recieved HN001 scored considerably lower on depression and anxiety. The prevention or treatment of postpartum anxiety and depression symptoms may benefit from this probiotic. | Lactobacillus rhamnosus HN001 | From enrolment until birth and, from birth up till six months post-birth whilst breastfeeding |
Rudzki et al., 2019 [57] | Randomised Double-blind Placebo-controlled Trial | Hamilton Depression Rating Scale (HAM-D 17)—clinical assessment; Symptom Checklist (SCL-90)—clinical assessment; Perceived Stress Scale (PSS-10)—self-reported; Attention and Perceptivity Test (APT)—clinical assessment; Stroop Test parts A and B—both experimental and clinical purposes; Trail Making Test (TMT) Parts A and B—clinical assessment; and the California Verbal Learning Test (CVLT)—clinical assessment | Probiotic bacteria Lactobacillus plantarum 299v added to SSRI therapy enhanced cognitive function and reduced KYN levels in MDD patients. In comparison to the placebo group, the LP299v group’s improved cognitive capabilities may have been caused by a decrease in KYN concentration. | Lactobacillus plantarum 299v | 8 weeks |
Romijn et al., 2017 [58] | Randomised Double-blind Placebo-controlled Trial | Montgomery–Asberg Depression Rating Scale (MADRS)—clinical assessment; Improved Clinical Global Impressions scale(iCGI)—clinical assessment; Quick Inventory of Depressive Symptomatology (QIDS-SR16)—self-assessment; Global Assessment of Functioning (GAF)—clinical assessment; Depression, Anxiety, and Stress Scale (DASS 42)—self-report; Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS)—clinical assessment | Regarding all psychological outcome measures and blood-based biomarkers, there was no discernible difference between the probiotic and placebo groups. At the halfway mark, nine (23%) of the probiotic group had a change of almost 60% on the Montgomery–Åsberg Depression Rating Scale (responders), while only 10 (26%) of the participants in the placebo group exhibited the same change. | Lactobacillus helveticus and Bifidobacterium longum | 8 weeks |
Morales-Torres et al., 2023 [59] | Randomized Placebo-Controlled Trial | Ryff wellbeing Scale (RYFF)—self-reported; Positive and Negative Affect Scales (PANAS)—self-reported; Satisfaction with Life Scale (SWLS)—self-reported; SF-36 Health Survey; the State–Trait Anxiety Inventory (STAI)—self-reported; Difficulties in Emotion Regulation Scale (DERS)—self-reported; Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire—self-reported; Five Facet Mindfulness Questionnaire (FFMQ)—self-reported | Findings indicated that the overall sample outcomes were not significantly impacted by probiotic consumption. Positive effects on anxiety, emotional regulation, and mindfulness in post-treatment outcomes were only predicted by the interaction between high healthy behaviors scores and probiotic intake, according to the linear mixed-effects model. | Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 | 4 weeks |
Miyaoka et al., 2018 [60] | Prospective open-label study | Diagnostic and Statistical Manual of Mental Disorders—clinical assessment; Hamilton Depression Rating Scale (HAMD-17)—clinical assessment; Beck Depression Inventory (BDI)—self-report rating inventory; Beck Anxiety Inventory (BAI)—self-report rating inventory | CBM 588 along with antidepressants provided considerable improvement in depression. | Clostridium butyricum MIYAIRI 588 | 8 weeks |
Ho et al., 2021 [61] | Randomized, Double-Blind, Placebo-Controlled Pilot Trial | Beck Depression Inventory (BDI-II)—self-report rating inventory; Beck Anxiety Inventory (BAI)—self-report rating inventory; Pittsburgh Sleep Quality Index (PSQI)—self-rated questionnaire; Insomnia Severity Index (ISI)—self-report questionnaire; Epworth sleepiness Scale (ESS)—self-assessment; Heart Rate Variability (HRV); Visual Analogue Scale (VAS)—self-reported; and State Trait Anxiety Inventory (STAI)—self-reported scale | The probiotic group showed important reduces in depression scores, which are related with changes in brain waves and sleep maintenance. | Lactobacillus plantarum PS128 | 30 days |
Haghighat et al., 2021 [62] | Randomized, Double-blinded, clinical trial | Hospital Anxiety and Depression Scale (HADS)—self-report rating scale | Synbiotic administration showed significant reduce in depression and anxiety symptoms and increase in the brain-derived neurotrophic factor (BDNF) | Synbiotic (15 g of prebiotics, 5 g of probiotic containing Lactobacillus acidophilus T16, Bifidobacterium bifidum BIA-6, Bifidobacterium lactis BIA-7, and Bifidobacterium longum BIA-8 (2.7 × 107 CFU/g each). Probiotics (5 g probiotics as in synbiotic group with 15 g of maltodextrin as placebo). | 12 weeks |
Gawlik-Kotelnicka et al., 2023 [63] | PRO-DEMET Randomized Controlled Trial | Montgomery– Asberg Depression Rating Scale (MADRS) —clinical assessment; Food Frequency Questionnaire by Wadołowska—self-reported; Depression Anxiety and Stress Scale (DASS)—self-reported; WHO Quality of Life BREF Instrument—self-report questionnaire | Probiotics have been demonstrated to be beneficial with minimal adjustment in depression cases with versus without metabolic syndrome. | Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175 | 60 days |
Dawe et al., 2020 [64] | Randomised Controlled Trial | Edinburgh Postnatal Depression Scale (EPDS)—self-reported; State–Trait Anxiety Inventory (STAI-6)—self-report scale; 12-Item Short-Form Health Survey (SF-12-v2)—self-reported | In this diverse group of obese pregnant women, probiotics had no effect on mental health outcomes. | Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 | 36 weeks of pregnancy |
Browne et al., 2021 [65] | Double-blind Randomized Pilot Trial | Edinburgh Postnatal Depression Scale (EPDS)—self-reported; State–Trait Anxiety Inventory (STAI)—self-report scale; MINI International Neuropsychiatric Interview | Secondary outcomes showed no significant difference between the probiotic and placebo groups on the subject of boosting maternal mood. | Bifidobacterium bifidum W23, Bifdobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58) | 26 to 30 weeks gestation until delivery |
Boehme et al., 2017, [66] | Randomized, Placebo-controlled, Two-arm, Parallel, Double-blind Clinical Trial | Maastricht Acute Stress Test (MAST)—clinical assessment; Depression, Anxiety, and Stress Scale (DASS-42)—self-report; Perceived Stress Scale (PSS)—self-reported; Hospital Anxiety and Depression Scales—self-report rating scale; Gastrointestinal Symptom Rating Scale (GSRS)—self-administered; Pittsburgh Sleep Quality Index (PSQI) —self-rated questionnaire | Probiotic intervention revealed a decrease in anxiety, depression, and the cortisol awakening response. | Bifidobacterium longum (BL) NCC3001 | 6 weeks |
Östlund-Lagerström et al., 2015 [67] | Double blind, Randomized, Placebo-Controlled Clinical Trial | Gastrointestinal symptoms rating scale (GSRS)—self-administered; Hospital anxiety and depression scale (HADS)—self-report rating scale; EQ-5D-5L, Perceived stress scale (PSS)—self-reported; Daily stool frequency, secondary questionnaires (e.g., HADS, PSS, EQ-5D-5L) | Neither probiotic or placebo treatment was found to be able to decrease symptoms of depression among participants suffering from gastrointestinal symptoms. Probiotic treatment has been found to have an influence on anxiety. | Freeze-dried L. reuteri DSM 17938, rhamnose, galactooligosaccharide, and maltodextrin | 12 weeks |
Lew et al., 2019 [68] | Randomised, Double-Blind, Placebo-Controlled Study | Cohen’s Perceived Stress Scale (PSS-10)—self-reported; DASS-21 stress questionnaire—self-reported; Perceived Stress Scale (PSS) questionnaire—self-reported; Depression, Anxiety, and Stress Scale (DASS-42) questionnaire—self-reported | Both placebo and P8 reduced stress levels and depression. P8 significantly exhibited lower scores as compared to the placebo for anxiety. | Probiotic Lactobacillus plantarum P8 | 12 weeks |
Mohammadi et al., 2015 [69] | Randomized, Double-Blind, Placebo-Controlled Trial in petrochemical workers | General health questionnaire (GHQ)—self-administered; Depression, Anxiety, and Stress scale (DASS) scores—self-reported | Beneficial effects of probiotic supplementation may be mediated through its effects on neuronal circuits and central nervous system mediated by microbiota–gut–brain axis and the regulation of GABA receptors by the vagus nerve, known as the major regulator of the interactions between gut microbiota and the brain. Probiotics may influence both the enteric immune system by modifying the GI tract microbiome. | Probiotic yogurt contained two strains of Lactobacillus acidophilus LA5 and Bifidobacterium lactis BB12. The multispecies probiotic capsule contained seven probiotic bacteria spices Actobacillus casei, L. acidophilus, L. rhamnosus, L. bulgaricus, Bifidobacterium breve, B. longum, S. thermophilus and fructo-oligosaccharide with lactose as carrier substances. | 6 weeks |
Raygan et al., 2018 [70] | Randomized, Double-blind, Placebo-Controlled Trial | Questionnaire for Beck Depression Inventory (BDI)—self-report rating inventory; Beck Anxiety Inventory (BAI)—self-report rating scale; General Health Questionnaire-28 (GHQ-28)—self-administered | Vitamin D supplementation reduces depression score. Probiotic might improve symptoms of mental health through elevated tryptophan concentrations and reduced serotonin levels. The synergism between the immunomodulatory and anti-inflammatory effects of both vitamin D and probiotic might boost their effect on clinical symptoms of psychiatric illnesses. | Probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum | 12 weeks |
Nikolova et al., 2023 [71] | Double-blind, placebo-controlled pilot randomized clinical trial | Hamilton Depression Rating Scale [HAMD-17]—clinical assessment; Inventory of Depressive Symptomatology [IDS]—self-reported; Hamilton Anxiety Rating Scale [HAMA]—clinical assessment; General Anxiety Disorder [GAD-7]—self-administered | The probiotic group attained greater improvements in both depressive symptoms scores, as well as anxiety symptoms in HAMA but not in GAD-7. | The probiotic contained 14 strains of Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis, and Streptococcus thermophilus | 8 weeks |
Hadi et al., 2019 [72] | Randomized double-blind, placebo-controlled trial | Depression Anxiety Stress Scale-21 (DASS-21)—self-reported | Significant between-group decrease in stress, anxiety, and depression was found in the synbiotic group. | Synbiotic in form of a capsule containing Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum plus inulin | 8 weeks |
Venkataraman et al., 2021 [73] | Double-Blind, Placebo-Controlled Study | Perceived stress scale (PSS)—self-reported; Depression, Anxiety, and Stress scale (DASS)—self-reported; State–Trait Anxiety Inventory (STAI)—self-report scale | Students who consumed probiotics, showed a significant reduction in depression and anxiety scores, serum cortisol levels from the baseline as compared with placebo. No adverse effects were noted. | Multi-strain probiotic (Bacillus coagulans Unique IS2, Lactobacillus rhamnosus UBLR58, Bifidobacterium lactis UBBLa70, Lactobacillus plantarum UBLP40, Bifidobacterium breve UBBr01, Bifidobacterium infantis UBBI01 with glutamine | 4 weeks |
Adikari et al., 2020 [74] | Randomized, double-blinded, placebo-controlled trial | Portable electrophysiological devices | Cognitive test reaction time showed significant improvement in the probiotic group. Probiotics may offer a psychological improvement to exercise. | Lactobacillus Casei Shirota strain | 8 weeks |
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Merkouris, E.; Mavroudi, T.; Miliotas, D.; Tsiptsios, D.; Serdari, A.; Christidi, F.; Doskas, T.K.; Mueller, C.; Tsamakis, K. Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials. Microorganisms 2024, 12, 411. https://doi.org/10.3390/microorganisms12020411
Merkouris E, Mavroudi T, Miliotas D, Tsiptsios D, Serdari A, Christidi F, Doskas TK, Mueller C, Tsamakis K. Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials. Microorganisms. 2024; 12(2):411. https://doi.org/10.3390/microorganisms12020411
Chicago/Turabian StyleMerkouris, Ermis, Theodora Mavroudi, Daniil Miliotas, Dimitrios Tsiptsios, Aspasia Serdari, Foteini Christidi, Triantafyllos K. Doskas, Christoph Mueller, and Konstantinos Tsamakis. 2024. "Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials" Microorganisms 12, no. 2: 411. https://doi.org/10.3390/microorganisms12020411