Probiotics in reducing anxiety and depression symptoms: an integrative review
Article Sidebar
Published:
Dec 14, 2020
Keywords:
anxiety, depression, intestinal microbiota, probiotics
Main Article Content
Abstract
Objectives: To summarize studies that evaluated probiotic supplementation as a therapeutic strategy for anxiety and depression symptoms. Methods: An integrative review of articles indexed in the PubMed, SciELO and Virtual Health Library databases published between January 2010 and September 2019. For this purpose, the combination of descriptors: “intestine”, “brain”, “Intestinal microbiota”, “anxiety”, “depression”, “probiotics”, in Portuguese and English. Results: After applying the inclusion and exclusion criteria, 13 randomized clinical trials were selected. The duration of the studies in its majority was 8 or 12 weeks (61.5%; n = 8), and the most offered form of the supplement was the probiotic powder (46.2%; n = 6) and capsule (30.8%; n = 4). Regarding the use of scales as a parameter for assessing symptoms of anxiety and depression, 38.5% (n = 5) used only one scale and 69.2% (n = 8) used the combination of two or three scales. Regarding the genus of bacteria, most studies used Lactobacillus and Bifidobacterium together (53.8%; n = 7). Despite methodological limitations and inconsistent results, most clinical trials (76.92%; n = 10) showed a significant reduction in symptoms related to anxiety and depression through probiotic supplementation. Conclusion: The evidence indicates that supplementation with probiotics has a potential in reducing symptoms of anxiety and depression, however further research is needed on this strategy as an adjunctive therapy in effective treatment for mental health.
Article Details
How to Cite
1.
Costa BC, Azevedo GS dos S, Ferreira PHA, Rodrigues Almeida LM. Probiotics in reducing anxiety and depression symptoms: an integrative review. Health Sci J [Internet]. 2020Dec.14 [cited 2024May12];10(4):97-108. Available from: https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/1014
Section
ORIGINAL ARTICLE
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors maintain copyright and grant the Health Sciences Journal the right to first publication. From 2024, the publications wiil be licensed under Attribution 4.0 International 
, allowing their sharing, recognizing the authorship and initial publication in this journal.
Authors are authorized to assume additional contracts separately for the non-exclusive distribution of the version of the work published in this journal (e.g., publishing in an institutional repository or as a book chapter), with acknowledgment of authorship and initial publication in this journal.
Authors are encouraged to publish and distribute their work online (e.g., in institutional repositories or on their personal page) at any point after the editorial process.
Also, the AUTHOR is informed and consents that the Health Sciences Journal can incorporate his article into existing or future scientific databases and indexers, under the conditions defined by the latter at all times, which will involve, at least, the possibility that the holders of these databases can perform the following actions on the article.
References
1. World Health Organization. Depression and other common mental disorders: global health estimates, [online]. Geneva: Switzerland; 2017 [cited 2020 Nov 12]. Avaiable from: https://apps.who.int/iris/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf
2. Friedrich MJ. Depression is the leading cause of disability around the world. JAMA. 2017;317(15):1517. https://doi.org/10.1001/jama.2017.3826
3. Murray E, Sharma R, Smith KB, Mar KD, Barve R, Lukasik M, et al. Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner. Brain Behav Immun. 2019;81:198-212. https://doi.org/10.1016/j.bbi.2019.06.016 PMid:31212008
4. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179-88. https://doi.org/10.1016/j.neuroscience.2010.08.005 PMid:20696216
5. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050-55. https://doi.org/10.1073/pnas.1102999108 PMid:21876150 PMCid:PMC3179073
6. Cryan JF, Dinan TG. Mindaltering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701-12. https://doi.org/10.1038/nrn3346 PMid:22968153
7. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268-73. https://doi.org/10.1126/science.1223490 PMCid:PMC4420145
8. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242-9. https://doi.org/10.1038/nature11552 PMid:22972297
9. Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK. Specialized metabolites from the microbiome in health and disease. Cell Metab. 2014;20(5):719-30. https://doi.org/10.1016/j.cmet.2014.10.016 PMid:25440054 PMCid:PMC4337795
10. Food and Agriculture Organization/World Health Organization. Working Group Report on drafting guidelines for the evaluation of probiotics in food [Internet]. London, Ontario, Canada; FAO/WHO; 2002 May [cited 2020 Nov 12]. Avaiable from: https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf
11. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74(10):720-6. https://doi.org/10.1016/j.biopsych.2013.05.001 PMid:23759244
12. Schousboe A, Waagepetersen HS. GABA: Homeostatic and pharmacological aspects. Prog Brain Res. 2007;160:9-19. https://doi.org/10.1016/S0079-6123(06)60002-2
13. Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. Bioessays. 2011;33(8):574-81. https://doi.org/10.1002/bies.201100024 PMid:21732396
14. Health Canada [Internet site]. Accepted claims about the nature of probiotic microorganisms in food. Health Canada; 2009 Apr 16 [cited 2020 Nov 12]. Avaiable from: https://bit.ly/32BfhyA
15. Savignac HM, Kiely B, Dinan TG, Cryan JF. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26(11):1615-27. https://doi.org/10.1111/nmo.12427 PMid:25251188
16. Savignac HM, Tramullas M, Kiely B, Dinan TG, Cryan JF. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res. 2015;287:59-72. https://doi.org/10.1016/j.bbr.2015.02.044 PMID: 25794930
17. Mulder IE, Schmidt B, Lewis M, Delday M, Stokes CR, Bailey M, et al. Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. PLoS One 2011;6(12):e28279. https://doi.org/10.1371/journal.pone.0028279 PMid:22216092 PMCid:PMC3245219
18. Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, et al. Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatr Allergy Immunol. 2012;23(3):265-9. https://doi.org/10.1111/j.1399-3038.2011.01258.x PMid:22300455
19. Butler JE, Weber P, Sinkora M, Baker D, Schoenherr A, Mayer B, et al. Antibody repertoire development in fetal and neonatal piglets. VIII. Colonization is required for newborn piglets to make serum antibodies to T-dependent and type 2 T-independent antigens. J Immunol. 2002;169(12):6822-30. https://doi.org/10.4049/jimmunol.169.12.6822 PMid:12471114
20. National Collaborating Centre for Methods and Tools [Internet]. Effective Public Health Practice Project. Quality assessment tool for quantitative studies. Hamilton, Ontario: Effective Public Health Practice Project; 1998 [cited 2002 Nov 12]. Avaiable from: https://merst.ca/ephpp/
21. Wang L, Zhang J, Guo Z, Kwok L, Ma C, Zhang W, et al. Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota, SIgA, SCFAs, and TBAs of adults of different ages. Nutrition. 2014;30(7-8):776-83.e1. https://doi.org/10.1016/j.nut.2013.11.018 PMid:24984992
22. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009;106(10):3698-03. https://doi.org/10.1073/pnas.0812874106 PMid:19234110 PMCid:PMC2656143
23. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364-71. https://doi.org/10.2337/db11-1019 PMid:22190648 PMCid:PMC3266401
24. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-76. https://doi.org/10.1016/j.cell.2015.02.047 PMid:25860609 PMCid:PMC4393509
25. Thayer JF, Sternberg EM. Neural concomitants of immunity: focus on the vagus nerve. Neuroimage. 2009;47(3):908-10. https://doi.org/10.1016/j.neuroimage.2009.05.058 PMid:19481613 PMCid:PMC2860274
26. Spalding TW, Jeffers LS, Porges SW, Hatfield BD. Vagal and cardiac reactivity to psychological stressors in trained and untrained men. Med Sci Sports Exerc. 2000;32(3):581-91. https://doi.org/10.1097/00005768-200003000-00006 PMid:10730999
27. Mezzacappa ES, Kelsey RM, Katkin ES, Sloan RP. Vagal rebound and recovery from psychological stress. Psychosom Med. 2001;63(4):650-57. https://doi.org/10.1097/00006842-200107000-00018 PMid:11485119
28. de Haan JJ, Hadfoune M, Lubbers T, Hodin C, Lenaerts K, Ito A, et al. Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex. Am J Physiol Gastrointest. Liver Physiol. 2013;305(5):G383-91. https://doi.org/10.1152/ajpgi.00333.2012 PMid:23812038
29. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458-62. https://doi.org/10.1038/35013070 PMid:10839541
30. Kirchner A, Birklein F, Stefan H, Handwerker HO. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2000;55(8):1167-71. https://doi.org/10.1212/WNL.55.8.1167 PMid:11071495
31. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, et al. Vagus nerve stimulation (VNSTM) for treatment-resistant depression: efficacy, side effects, and pre-dictors of outcome. Neuropsychopharmacology. 2001;25(5):713-28. https://doi.org/10.1016/S0893-133X(01)00271-8
32. Salam OMA. Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats. Pharmacol Res. 2004;50(3):309-16. https://doi.org/10.1016/j.phrs.2004.01.010 PMid:15225675
33. Smith R, Allen JJ, Thayer JF, Fort C, Lane RD. Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression. Psychiatry Res. 2014;224(3):225-33. https://doi.org/10.1016/j.pscychresns.2014.08.015 PMid:25282511
34. Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. 2016;39(11):763-81. https://doi.org/10.1016/j.tins.2016.09.002 PMid:27793434 PMCid:PMC5102282
35. O'Mahony, L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541-51. https://doi.org/10.1053/j.gastro.2004.11.050 PMid:15765388
36. Chu H, Mazmanian SK. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat Immunol. 2013;14(7):668-75. https://doi.org/10.1038/ni.2635 PMid:23778794 PMCid:PMC4109969
37. Zhou W, Lv H, Li MX, Su H, Huang LG, Li J, et al. Protective effects of bifidobacteria on intestines in newborn rats with necrotizing enterocolitis and its regulation on TLR2 and TLR4. Genet Mol Res. 2015;14(3):11505-14. https://doi.org/10.4238/2015.September.28.2 PMid:26436391
38. Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8(20):1-27. https://doi.org/10.1017/S1462399406000068 PMid:16942634
39. Myint AM, Kym YK, Verkerk R, Scharpé S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007;98(1-2):143-51. https://doi.org/10.1016/j.jad.2006.07.013 PMid:16952400
40. Desbonnet L, Garret L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 2008;43(2):164-74. https://doi.org/10.1016/j.jpsychires.2008.03.009 PMid:18456279
41. Mohammadi AA, Jazayeri S, Khosravi-Darani K, Solati Z, Mohammadpour N, Asemi Z, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. 2016;19(9):387-95. https://doi.org/10.1179/1476830515Y.0000000023 PMid:25879690
42. Nishihira J, Kagami-Katsuyama H, Tanaka A, Nishimura M, Kobayashi T, Kawasaki Y. Elevation of natural killer cell activity and alleviation of mental stress by the consumption of yogurt containing Lactobacillus gasseri SBT2055 and Bifidobacterium longum SBT2928 in a double-blind, placebo-controlled clinical trial. J Funct Foods. 2014;11:261-68. https://doi.org/10.1016/j.jff.2014.09.002
43. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755-64. https://doi.org/10.1017/S0007114510004319 PMid:20974015
44. 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. 2015;48:258-64. https://doi.org/10.1016/j.bbi.2015.04.003 PMid:25862297
45. 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. 2017;51(8):810-21. https://doi.org/10.1177/0004867416686694 PMid:28068788 PMCid:PMC5518919
46. Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, et al. 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. 2019;38(5):2053-64. https://doi.org/10.1016/j.clnu.2018.09.010 PMid:30266270
47. Wang Y, Telesford KM, Ochoa-Reparaz J, Haque-Begum S, Christy M, Kasper EJ, Wang L. An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun. 2014;5:4432. https://doi.org/10.1038/ncomms5432 PMid:25043484 PMCid:PMC4118494
48. Kwok LY, Guo Z, Zhang J, Wang L, Qiao J, Hou Q, et al. The impact of oral consumption of Lactobacillus plantarum P-8 on faecal bacteria revealed by pyrosequencing. Benef Microbes. 2015;6(4):405-13. https://doi.org/10.3920/BM2014.0063 PMid:25653153
49. Akkasheh G, Kashani-Poor Z, Tajabadi-ebrahimi M, Jafari P, Akbari H, Taghizadeh M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutr. 2016;32(3):315-20. https://doi.org/10.1016/j.nut.2015.09.003 PMid:26706022
50. Rudzki L, Ostrowska L, Pawlak D, Malus A, Pawlak K, Waszkiewicz N, et al. Probiotic Lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo-controlled study. Psychoneuroendocrinology. 2019;100:213-22. https://doi.org/10.1016/j.psyneuen.2018.10.010 PMid:30388595
51. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13(7):465-77. https://doi.org/10.1038/nrn3257 PMid:22678511 PMCid:PMC3681811
52. Steiner J, Walter M, Gos T, Guillemin GJ, Bernstein HG, Sarnyai Z, et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? J Neuroinflammation. 2011;8:94. https://doi.org/10.1186/1742-2094-8-94 PMid:21831269 PMCid:PMC3177898
53. Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M. IDO and interferonalpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol psychiatry. 2005;10(6):538-44. https://doi.org/10.1038/sj.mp.4001600 PMid:15494706
54. Chahwan B, Kwan S, Isik A, Van hemert S, Burke C, Roberts L. Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms. J Affect Disord. 2019;253:317-26. https://doi.org/10.1016/j.jad.2019.04.097 PMid:31078831
55. Pinto-sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448-459.e8. https://doi.org/10.1053/j.gastro.2017.05.003 PMid:28483500
56. Lyra A, Hillila M, Huttunen T, Männikkö S, Taalikka M, Tennilä J, et al. Irritable bowel syndrome symptom severity improves equally with probiotic and placebo. World J Gastroenterol. 2016;22(48):10631-42. https://doi.org/10.3748/wjg.v22.i48.10631 PMid:28082816 PMCid:PMC5192275
57. Yang H, Zhao X, Tang S, Huang H, Ning Z, Fu X, et al. Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia Pac J Clin Oncol. 2016;12(1):e92-6. https://doi.org/10.1111/ajco.12120 PMid:24571169
58. Chung YC, Jin HM, Cui Y, Kim DS, Jung JM, Park JI, et al. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J Funct Foods. 2014;10:465-74. https://doi.org/10.1016/j.jff.2014.07.007
2. Friedrich MJ. Depression is the leading cause of disability around the world. JAMA. 2017;317(15):1517. https://doi.org/10.1001/jama.2017.3826
3. Murray E, Sharma R, Smith KB, Mar KD, Barve R, Lukasik M, et al. Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner. Brain Behav Immun. 2019;81:198-212. https://doi.org/10.1016/j.bbi.2019.06.016 PMid:31212008
4. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179-88. https://doi.org/10.1016/j.neuroscience.2010.08.005 PMid:20696216
5. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050-55. https://doi.org/10.1073/pnas.1102999108 PMid:21876150 PMCid:PMC3179073
6. Cryan JF, Dinan TG. Mindaltering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701-12. https://doi.org/10.1038/nrn3346 PMid:22968153
7. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268-73. https://doi.org/10.1126/science.1223490 PMCid:PMC4420145
8. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242-9. https://doi.org/10.1038/nature11552 PMid:22972297
9. Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK. Specialized metabolites from the microbiome in health and disease. Cell Metab. 2014;20(5):719-30. https://doi.org/10.1016/j.cmet.2014.10.016 PMid:25440054 PMCid:PMC4337795
10. Food and Agriculture Organization/World Health Organization. Working Group Report on drafting guidelines for the evaluation of probiotics in food [Internet]. London, Ontario, Canada; FAO/WHO; 2002 May [cited 2020 Nov 12]. Avaiable from: https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf
11. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74(10):720-6. https://doi.org/10.1016/j.biopsych.2013.05.001 PMid:23759244
12. Schousboe A, Waagepetersen HS. GABA: Homeostatic and pharmacological aspects. Prog Brain Res. 2007;160:9-19. https://doi.org/10.1016/S0079-6123(06)60002-2
13. Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. Bioessays. 2011;33(8):574-81. https://doi.org/10.1002/bies.201100024 PMid:21732396
14. Health Canada [Internet site]. Accepted claims about the nature of probiotic microorganisms in food. Health Canada; 2009 Apr 16 [cited 2020 Nov 12]. Avaiable from: https://bit.ly/32BfhyA
15. Savignac HM, Kiely B, Dinan TG, Cryan JF. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26(11):1615-27. https://doi.org/10.1111/nmo.12427 PMid:25251188
16. Savignac HM, Tramullas M, Kiely B, Dinan TG, Cryan JF. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res. 2015;287:59-72. https://doi.org/10.1016/j.bbr.2015.02.044 PMID: 25794930
17. Mulder IE, Schmidt B, Lewis M, Delday M, Stokes CR, Bailey M, et al. Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. PLoS One 2011;6(12):e28279. https://doi.org/10.1371/journal.pone.0028279 PMid:22216092 PMCid:PMC3245219
18. Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, et al. Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatr Allergy Immunol. 2012;23(3):265-9. https://doi.org/10.1111/j.1399-3038.2011.01258.x PMid:22300455
19. Butler JE, Weber P, Sinkora M, Baker D, Schoenherr A, Mayer B, et al. Antibody repertoire development in fetal and neonatal piglets. VIII. Colonization is required for newborn piglets to make serum antibodies to T-dependent and type 2 T-independent antigens. J Immunol. 2002;169(12):6822-30. https://doi.org/10.4049/jimmunol.169.12.6822 PMid:12471114
20. National Collaborating Centre for Methods and Tools [Internet]. Effective Public Health Practice Project. Quality assessment tool for quantitative studies. Hamilton, Ontario: Effective Public Health Practice Project; 1998 [cited 2002 Nov 12]. Avaiable from: https://merst.ca/ephpp/
21. Wang L, Zhang J, Guo Z, Kwok L, Ma C, Zhang W, et al. Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota, SIgA, SCFAs, and TBAs of adults of different ages. Nutrition. 2014;30(7-8):776-83.e1. https://doi.org/10.1016/j.nut.2013.11.018 PMid:24984992
22. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009;106(10):3698-03. https://doi.org/10.1073/pnas.0812874106 PMid:19234110 PMCid:PMC2656143
23. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364-71. https://doi.org/10.2337/db11-1019 PMid:22190648 PMCid:PMC3266401
24. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-76. https://doi.org/10.1016/j.cell.2015.02.047 PMid:25860609 PMCid:PMC4393509
25. Thayer JF, Sternberg EM. Neural concomitants of immunity: focus on the vagus nerve. Neuroimage. 2009;47(3):908-10. https://doi.org/10.1016/j.neuroimage.2009.05.058 PMid:19481613 PMCid:PMC2860274
26. Spalding TW, Jeffers LS, Porges SW, Hatfield BD. Vagal and cardiac reactivity to psychological stressors in trained and untrained men. Med Sci Sports Exerc. 2000;32(3):581-91. https://doi.org/10.1097/00005768-200003000-00006 PMid:10730999
27. Mezzacappa ES, Kelsey RM, Katkin ES, Sloan RP. Vagal rebound and recovery from psychological stress. Psychosom Med. 2001;63(4):650-57. https://doi.org/10.1097/00006842-200107000-00018 PMid:11485119
28. de Haan JJ, Hadfoune M, Lubbers T, Hodin C, Lenaerts K, Ito A, et al. Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex. Am J Physiol Gastrointest. Liver Physiol. 2013;305(5):G383-91. https://doi.org/10.1152/ajpgi.00333.2012 PMid:23812038
29. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458-62. https://doi.org/10.1038/35013070 PMid:10839541
30. Kirchner A, Birklein F, Stefan H, Handwerker HO. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2000;55(8):1167-71. https://doi.org/10.1212/WNL.55.8.1167 PMid:11071495
31. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, et al. Vagus nerve stimulation (VNSTM) for treatment-resistant depression: efficacy, side effects, and pre-dictors of outcome. Neuropsychopharmacology. 2001;25(5):713-28. https://doi.org/10.1016/S0893-133X(01)00271-8
32. Salam OMA. Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats. Pharmacol Res. 2004;50(3):309-16. https://doi.org/10.1016/j.phrs.2004.01.010 PMid:15225675
33. Smith R, Allen JJ, Thayer JF, Fort C, Lane RD. Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression. Psychiatry Res. 2014;224(3):225-33. https://doi.org/10.1016/j.pscychresns.2014.08.015 PMid:25282511
34. Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. 2016;39(11):763-81. https://doi.org/10.1016/j.tins.2016.09.002 PMid:27793434 PMCid:PMC5102282
35. O'Mahony, L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541-51. https://doi.org/10.1053/j.gastro.2004.11.050 PMid:15765388
36. Chu H, Mazmanian SK. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat Immunol. 2013;14(7):668-75. https://doi.org/10.1038/ni.2635 PMid:23778794 PMCid:PMC4109969
37. Zhou W, Lv H, Li MX, Su H, Huang LG, Li J, et al. Protective effects of bifidobacteria on intestines in newborn rats with necrotizing enterocolitis and its regulation on TLR2 and TLR4. Genet Mol Res. 2015;14(3):11505-14. https://doi.org/10.4238/2015.September.28.2 PMid:26436391
38. Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8(20):1-27. https://doi.org/10.1017/S1462399406000068 PMid:16942634
39. Myint AM, Kym YK, Verkerk R, Scharpé S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007;98(1-2):143-51. https://doi.org/10.1016/j.jad.2006.07.013 PMid:16952400
40. Desbonnet L, Garret L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 2008;43(2):164-74. https://doi.org/10.1016/j.jpsychires.2008.03.009 PMid:18456279
41. Mohammadi AA, Jazayeri S, Khosravi-Darani K, Solati Z, Mohammadpour N, Asemi Z, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. 2016;19(9):387-95. https://doi.org/10.1179/1476830515Y.0000000023 PMid:25879690
42. Nishihira J, Kagami-Katsuyama H, Tanaka A, Nishimura M, Kobayashi T, Kawasaki Y. Elevation of natural killer cell activity and alleviation of mental stress by the consumption of yogurt containing Lactobacillus gasseri SBT2055 and Bifidobacterium longum SBT2928 in a double-blind, placebo-controlled clinical trial. J Funct Foods. 2014;11:261-68. https://doi.org/10.1016/j.jff.2014.09.002
43. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755-64. https://doi.org/10.1017/S0007114510004319 PMid:20974015
44. 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. 2015;48:258-64. https://doi.org/10.1016/j.bbi.2015.04.003 PMid:25862297
45. 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. 2017;51(8):810-21. https://doi.org/10.1177/0004867416686694 PMid:28068788 PMCid:PMC5518919
46. Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, et al. 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. 2019;38(5):2053-64. https://doi.org/10.1016/j.clnu.2018.09.010 PMid:30266270
47. Wang Y, Telesford KM, Ochoa-Reparaz J, Haque-Begum S, Christy M, Kasper EJ, Wang L. An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun. 2014;5:4432. https://doi.org/10.1038/ncomms5432 PMid:25043484 PMCid:PMC4118494
48. Kwok LY, Guo Z, Zhang J, Wang L, Qiao J, Hou Q, et al. The impact of oral consumption of Lactobacillus plantarum P-8 on faecal bacteria revealed by pyrosequencing. Benef Microbes. 2015;6(4):405-13. https://doi.org/10.3920/BM2014.0063 PMid:25653153
49. Akkasheh G, Kashani-Poor Z, Tajabadi-ebrahimi M, Jafari P, Akbari H, Taghizadeh M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutr. 2016;32(3):315-20. https://doi.org/10.1016/j.nut.2015.09.003 PMid:26706022
50. Rudzki L, Ostrowska L, Pawlak D, Malus A, Pawlak K, Waszkiewicz N, et al. Probiotic Lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo-controlled study. Psychoneuroendocrinology. 2019;100:213-22. https://doi.org/10.1016/j.psyneuen.2018.10.010 PMid:30388595
51. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13(7):465-77. https://doi.org/10.1038/nrn3257 PMid:22678511 PMCid:PMC3681811
52. Steiner J, Walter M, Gos T, Guillemin GJ, Bernstein HG, Sarnyai Z, et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? J Neuroinflammation. 2011;8:94. https://doi.org/10.1186/1742-2094-8-94 PMid:21831269 PMCid:PMC3177898
53. Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M. IDO and interferonalpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol psychiatry. 2005;10(6):538-44. https://doi.org/10.1038/sj.mp.4001600 PMid:15494706
54. Chahwan B, Kwan S, Isik A, Van hemert S, Burke C, Roberts L. Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms. J Affect Disord. 2019;253:317-26. https://doi.org/10.1016/j.jad.2019.04.097 PMid:31078831
55. Pinto-sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448-459.e8. https://doi.org/10.1053/j.gastro.2017.05.003 PMid:28483500
56. Lyra A, Hillila M, Huttunen T, Männikkö S, Taalikka M, Tennilä J, et al. Irritable bowel syndrome symptom severity improves equally with probiotic and placebo. World J Gastroenterol. 2016;22(48):10631-42. https://doi.org/10.3748/wjg.v22.i48.10631 PMid:28082816 PMCid:PMC5192275
57. Yang H, Zhao X, Tang S, Huang H, Ning Z, Fu X, et al. Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia Pac J Clin Oncol. 2016;12(1):e92-6. https://doi.org/10.1111/ajco.12120 PMid:24571169
58. Chung YC, Jin HM, Cui Y, Kim DS, Jung JM, Park JI, et al. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J Funct Foods. 2014;10:465-74. https://doi.org/10.1016/j.jff.2014.07.007