A systematic review of the effects of probiotics on depression and anxiety: an alternative therapy?

Minayo, Miryam de Souza; Miranda, Iasmim; Telhado, Raquel Senna

doi:10.1590/1413-81232021269.21342020

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FREE THEMES • Ciênc. saúde coletiva 26 (09) • Sept 2021 • https://doi.org/10.1590/1413-81232021269.21342020 copy

A systematic review of the effects of probiotics on depression and anxiety: an alternative therapy?

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Abstract

This review aims to understand and analyse the effects of probiotics on depression, anxiety and psychological stress. These disorders are among the leading causes of disability worldwide. Conventional pharmacotherapies usually have a poor response or adverse side effects. In this context, recent studies have demonstrated a dense bi-directional communication named gut-brain axis. Evidences are demonstrating the relationship between disturbance in the enteric microbiome and psychiatric disorders, paving the way for the emergence of alternative therapies. A systematic search for randomized double/triple blind placebo-controlled clinical trials was performed in PubMed, Scopus and Lilacs. The studies selection followed the recommendations of the main items for report systematic reviews and meta-analyses (PRISMA). Nine articles met the criteria and were analysed for effects on depression, anxiety, psychological stress and biomarkers. Seven found positive results in at least one of the items. We concluded that the use of probiotics to alleviate depressive symptoms and anxiety is promising, mainly due to its potential anti-inflammatory effect, but additional and more rigorous double blind randomized clinical trials are necessary to endorse such conclusions.

Key words:
Depression; Anxiety; Probiotics; Microbiota; Gut-brain axis

Authors, year	Sample Characteristics	Number of individuals	Study design	Duration of intervention	Bacteria species and dose (CFU)	Administration mode	Psychological symptom / scale / biomarker	Outcome/main findings
Chong et al., 2019¹⁹19 Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, Yusoff MSB, Wahid N, Abdullah MFIL, Zakaria N, Ong KL, Park YH, Liong MT. Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study. Benef Microbes [periódico na Internet]. 2019 mar. [cited 2020 Apr. 16]; 10(4):355-373. Available from: https://pubmed.ncbi.nlm.nih.gov/30882244/ https://pubmed.ncbi.nlm.nih.gov/30882244...	Moderately stressed adults (18 to 60 years)	111	Double-blind, randomized, placebo-controlled	12 weeks	1x 10⁹ UFC of L. plantarum DR7	Sachet	Anxiety and depression/DASS-42 Stress/PSS-10 and DASS-42 Memory and cognition/CBB Plasma biomarkers	Improved stress levels (DASS-42) and anxiety. No effect on depression. Improved memory and cognition and in biomarkers.
Tran et a.l, 2019²⁰20 Tran N, Zhebrak M, Yacoub C, Pelletier J, Hawley D. The gut-brain relationship: Investigating the effect of multispecies probiotics on anxiety in a randomized placebo-controlled trial of healthy young adults. J Affect Disord [periódico na internet] 2019 jun. [cited 2020 Apr. 16]; 252:271-277. Available from: https://pubmed.ncbi.nlm.nih.gov/30991255/ https://pubmed.ncbi.nlm.nih.gov/30991255...	Healthy adults, mean age 20.59 years (18-31 years)	86	Double-blind, randomized, placebo-controlled	4 weeks	A. 50 x 109 UFC of 18 strains; B. 50 x 109 UFC of 10 strains; C. 15 x 109 UFC of 18 strains; E. 10 x 109 UFC of 10 strains.	Tablet	Anxiety / BAI, ACQ-R State of mind / PANAS Negative mood regulation / NMR Preoccupation / PSWQ	Improved anxiety, negative affectivity, mood regulation.
Lew et al., 2018²¹21 Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, Ahmad A, Mohammad JAM, Abdullah MFIL, Zakaria N, Wahid N, Sun Z, Kwok LY, Zhang H, Liong MT. Probiotic Lactobacillus plantarum P8 alleviated stress and anxiety while enhancing memory and cognition in stressed adults: A randomised, double-blind, placebo-controlled study. Clin Nutr [periódico na Internet] 2019 out. [cited 2020 Apr. 17]; 38(5):2053-2064. Available from: https://pubmed.ncbi.nlm.nih.gov/30266270/ https://pubmed.ncbi.nlm.nih.gov/30266270...	Stressed adults, mean age of 31.7 years (18-60 years)	103	Double-blind, randomized, placebo-controlled	12 weeks	2x 10¹⁰ UFC of L. plantarum P8	Sachet	Anxiety and depression/DASS-42 Stress/PSS-10 and DASS-42 Plasma biomarkers	Improved stress levels (DASS-42). Insignificant effect on depression and marginal effect on anxiety. Improved biomarkers.
Kelly et al., 2017²²22 Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, Murphy E, Boylan G, Bienenstock J, Cryan JF, Clarke G, Dinan TG. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun [periódico na Internet] 2017 mar. [cited 2020 Apr. 19]; 61:50-59. Available from: https://pubmed.ncbi.nlm.nih.gov/27865949/ https://pubmed.ncbi.nlm.nih.gov/27865949...	Male healthy adults (20-33 years)	29	Cross-sectional, double-blind, randomized, placebo-controlled	4 weeks	1 x 10⁹ UFC of L. rhamnosusJB-1	Capsule	Stress / BDI, SCL-90 BAI, SAI, TAI, PSS-10, PSQI, SECPT Cognitive impairment / CANTAB Plasma biomarkers	Unchanged
Romijn et. al 2017²³23 Romijn AR, Rucklidge JJ, Kuijer RG, Frampton C. A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Aust N Z J Psychiatry [periódico na Internet] 2017 ago. [cited 2020 Apr. 22]; 51(8):810-821. Available from: https://pubmed.ncbi.nlm.nih.gov/28068788/ https://pubmed.ncbi.nlm.nih.gov/28068788...	Adults with moderate mood swings (> 16 years)	79	Double-blind, randomized, placebo-controlled	8 weeks	3 x 10⁹ UFC of L. helveticus R0052 e B. longun R0175	Sachet	Depression / QIDS-SR16, DASS-42, MADRS, iCGI Anxiety / DASS-42 Plasma biomarkers	Unchanged
Akkasheh et al., 2016²⁴24 Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition [periódico na Internet] 2016 mar. [cited 2020 Apr. 23]; 32(3):315-320. Available from: https://pubmed.ncbi.nlm.nih.gov/26706022/ https://pubmed.ncbi.nlm.nih.gov/26706022...	Adults diagnosed with depression (20-55 years)	40	Double-blind, randomized, placebo-controlled	8 weeks	2x 109 UFC of each strain: L. acidophilus, L. casei and B. bifidum	Capsule	Depression / BDI Plasma biomarkers	Improved depression scale (BDI) and plasma biomarkers
Mohammadi et al., 2016²⁵25 Mohammadi AA, Jazayeri S, Khosravi-Darani K, Solati Z, Mohammadpour N, Asemi Z, Adab Z, Djalali M, Tehrani-Doost M, Hosseini M, Eghtesadi S. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci [periódico na Internet] 2016 nov. [cited 2020 Apr. 25]; 19(9):387-395. Available from: https://pubmed.ncbi.nlm.nih.gov/25879690/ https://pubmed.ncbi.nlm.nih.gov/25879690...	Healthy adult petrochemical workers	70	Double-blind, randomized, placebo-controlled	6 weeks	Probiotic yogurt: 1x 107 UFC/ml of L. acidophilus LA5 and B. lactis BB12 Probiotic capsule: L. casei 3 × 103 L. acidophilus 3 × 107, L. Rhamnosus 7 × 109, L. bulgaricus 5 × 108, B. breve 2 × 1010, B. longum 1 × 109, S. thermophilus 3 × 108 UFC/g	Yogurt and capsule	Depression, anxiety and stress / DASS and GHQ Plasma biomarkers	Improved mental health. No effect on the HPA axis.
Takada et al., 2016²⁶26 Takada M, Nishida K, Kataoka-Kato A, Gondo Y, Ishikawa H, Suda K, Kawai M, Hoshi R, Watanabe O, Igarashi T, Kuwano Y, Miyazaki K, Rokutan K. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterol Motil [periódico na Internet] 2016 jul. [cited 2020 Apr. 21]; 28(7):1027-1036. Available from: https://pubmed.ncbi.nlm.nih.gov/26896291/ https://pubmed.ncbi.nlm.nih.gov/26896291...	Healthy adults (< 30 years)	140	Three double-blind, randomized, placebo-controlled trials, in a parallel group	8 weeks	1x109 UFC of L. casei Shirota YIT 9029	Milk	Stress and anxiety/STAI, HHQ, Saliva biomarker	Improved physical symptoms related to stress and anxiety and improved biomarker.
Steenbergen et al., 2015²⁷27 Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood Brain Behav Immun [periódico na Internet]. 2015 ago. [cited 2020 Apr. 28]; 48:258-264. Available from: https://pubmed.ncbi.nlm.nih.gov/25 862297/ https://pubmed.ncbi.nlm.nih.gov/25 86229...	Healthy adults, mean age 19.7 years of the placebo group and 20.2 years of the probiotic group	40	Randomized triple-blind placebo-controlled pre and post intervention	4 weeks	2.5 x 109 UFC/g de B. bifidum W23, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, and Lactococcus lactis W19 e W58.	Sachet	Depression/LEIDS-r, BDI -II Anxiety / BAI	Improved depression and no effect on anxiety.

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[1] Collaborations

MS Minayo worked on the conception, methodological design, research, data analysis, writing and final revision of the text. I Miranda worked on the conception and analysis of the data. RS Telhado worked on the final revision of the manuscript.