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Assessment of optimal combinations of therapeutic probiotics for depression, anxiety, and stress

Published online by Cambridge University Press:  18 March 2024

Yafang Yang ,
Ligang Yang ,
Min Wan ,
Da Pan ,
Guiju Sun  and
Chao Yang Open the ORCID record for Chao Yang [Opens in a new window]
Yafang Yang
Affiliation:
Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
Ligang Yang
Affiliation:
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
Min Wan
Affiliation:
Rongxiang Community Health Service Center, Wuxi 214000, China
Da Pan
Affiliation:
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
Guiju Sun
Affiliation:
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
Chao Yang*
Affiliation:
Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
*
Corresponding author: Chao Yang; Email: chaoyang@jiangnan.edu.cn
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Abstract

Background

Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis.

Method

A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate.

Results

We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = −0.80; 95% CI −1.49 to −0.11), followed by Lactobacillus (SMD = −0.49; 95% CI −0.85 to −0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = −0.41; 95% CI −0.73 to −0.10) had a positive effect on depression.

Conclusion

The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.

Keywords

anxietydepressionnetwork meta-analysisprobioticsstress
Type
Original Article
Information
Psychological Medicine , Volume 54 , Issue 10 , July 2024 , pp. 2547 - 2561
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press

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References

Ait-Belgnaoui, A., Colom, A., Braniste, V., Ramalho, L., Marrot, A., Cartier, C., … Tompkins, T. (2014). Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterology And Motility, 26(4), 510–520. doi: 10.1111/nmo.12295CrossRefGoogle ScholarPubMed
Altemus, M., Sarvaiya, N., & Neill Epperson, C. (2014). Sex differences in anxiety and depression clinical perspectives. Frontiers in Neuroendocrinology, 35(3), 320–330. doi: 10.1016/j.yfrne.2014.05.004CrossRefGoogle ScholarPubMed
Amitai, M., Taler, M., Carmel, M., Michaelovsky, E., Eilat, T., Yablonski, M., … Fennig, S. (2016). The relationship between plasma cytokine levels and response to selective serotonin reuptake inhibitor treatment in children and adolescents with depression and/or anxiety disorders. Journal of Child and Adolescent Psychopharmacology, 26(8), 727–732. doi: 10.1089/cap.2015.0147CrossRefGoogle ScholarPubMed
Binda, S., Hill, C., Johansen, E., Obis, D., Pot, B., Sanders, M. E., … Ouwehand, A. C. (2020). Criteria to qualify microorganisms as “probiotic” in foods and dietary supplements. Frontiers in Microbiology, 11, 1662. doi: 10.3389/fmicb.2020.01662CrossRefGoogle ScholarPubMed
Bisson, J. F., Hidalgo, S., Rozan, P., & Messaoudi, M. (2010). Preventive effects of different probiotic formulations on travelers' diarrhea model in wistar rats: Preventive effects of probiotics on TD. Digestive Diseases And Sciences, 55(4), 911–919. doi: 10.1007/s10620-009-0822-4CrossRefGoogle ScholarPubMed
Boger, M. C. L., Lammerts van Bueren, A., & Dijkhuizen, L. (2018). Cross-feeding among probiotic bacterial strains on prebiotic inulin involves the extracellular exo-Inulinase of Lactobacillus paracasei strain W20. Applied And Environmental Microbiology, 84(21), e01539–e01518. doi: 10.1128/aem.01539-18CrossRefGoogle ScholarPubMed
Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., … Cryan, J. F. (2011). Ingestion of lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of The National Academy of Sciences of The United States of America, 108(38), 16050–16055. doi: 10.1073/pnas.1102999108CrossRefGoogle Scholar
Brignardello-Petersen, R., Florez, I. D., Izcovich, A., Santesso, N., Hazlewood, G., Alhazanni, W., … Guyatt, G. H. (2020). GRADE Approach to drawing conclusions from a network meta-analysis using a minimally contextualised framework. British Medical Journal, 371, m3900. doi: 10.1136/bmj.m3900CrossRefGoogle ScholarPubMed
Campos, A. C., Rocha, N. P., Nicoli, J. R., Vieira, L. Q., Teixeira, M. M., & Teixeira, A. L. (2016). Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice. Behavioural Brain Research, 312, 186–194. doi: 10.1016/j.bbr.2016.06.027CrossRefGoogle ScholarPubMed
Chaimani, A., Higgins, J. P., Mavridis, D., Spyridonos, P., & Salanti, G. (2013). Graphical tools for network meta-analysis in STATA. PLoS ONE, 8(10), e76654. doi: 10.1371/journal.pone.0076654CrossRefGoogle Scholar
Chen, Y. H., Bai, J., Wu, D., Yu, S. F., Qiang, X. L., Bai, H., … Peng, Z. W. (2019). Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. Journal of Affective Disorders, 259, 56–66. doi: 10.1016/j.jad.2019.08.014CrossRefGoogle ScholarPubMed
Cipriani, A., Higgins, J. P., Geddes, J. R., & Salanti, G. (2013). Conceptual and technical challenges in network meta-analysis. Annals of Internal Medicine, 159(2), 130–137. doi: 10.7326/0003-4819-159-2-201307160-00008CrossRefGoogle ScholarPubMed
Cukrowska, B., Bierła, J. B., Zakrzewska, M., Klukowski, M., & Maciorkowska, E. (2020). The relationship between the infant gut microbiota and allergy. The role of Bifidobacterium breve and prebiotic oligosaccharides in the activation of anti-allergic mechanisms in early life. Nutrients, 12(4), 946. doi: 10.3390/nu12040946CrossRefGoogle ScholarPubMed
Cumpston, M., Li, T., Page, M. J., Chandler, J., Welch, V. A., Higgins, J. P., & Thomas, J. (2019). Updated guidance for trusted systematic reviews: A new edition of the cochrane handbook for systematic reviews of interventions. Cochrane Database of Systematic Reviews, 10(10), Ed000142. doi: 10.1002/14651858.Ed000142Google ScholarPubMed
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019). The role of short-chain fatty acids in microbiota-gut-brain communication. Nature Reviews Gastroenterology & Hepatology, 16(8), 461–478. doi: 10.1038/s41575-019-0157-3CrossRefGoogle ScholarPubMed
DerSimonian, R. (1996). Meta-analysis in the design and monitoring of clinical trials. Statistics in Medicine, 15(12), 1237–1248. doi: 10.1002/(sici)1097-0258(19960630)15:12<1237::Aid-sim301>3.0.Co;2-n3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Desbonnet, L., Garrett, L., Clarke, G., Kiely, B., Cryan, J. F., & Dinan, T. G. (2010). Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience, 170(4), 1179–1188. doi: 10.1016/j.neuroscience.2010.08.005CrossRefGoogle ScholarPubMed
Dias, S., Welton, N. J., Caldwell, D. M., & Ades, A. E. (2010). Checking consistency in mixed treatment comparison meta-analysis. Statistics in Medicine, 29(7-8), 932–944. doi: 10.1002/sim.3767CrossRefGoogle ScholarPubMed
Douillard, F. P., Mora, D., Eijlander, R. T., Wels, M., & de Vos, W. M. (2018). Comparative genomic analysis of the multispecies probiotic-marketed product VSL#3. PLoS ONE, 13(2), e0192452. doi: 10.1371/journal.pone.0192452CrossRefGoogle ScholarPubMed
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of Stress, 7, 124–136. doi: 10.1016/j.ynstr.2017.03.001CrossRefGoogle ScholarPubMed
Guo, L., Ren, L., & Zhang, C. (2018). Relationship between depression and inflammatory factors and brain-derived neurotrophic factor in patients with perimenopause syndrome. Experimental And Therapeutic Medicine, 15(5), 4436–4440. doi: 10.3892/etm.2018.5985Google ScholarPubMed
Han, S., Lu, Y., Xie, J., Fei, Y., Zheng, G., Wang, Z., … Li, L. (2021). Probiotic gastrointestinal transit and colonization after oral administration: A long journey. Frontiers in Cellular And Infection Microbiology, 11, 609722. doi: 10.3389/fcimb.2021.609722CrossRefGoogle ScholarPubMed
Hutton, B., Salanti, G., Caldwell, D. M., Chaimani, A., Schmid, C. H., Cameron, C., … Moher, D. (2015). The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations. Annals of Internal Medicine, 162(11), 777–784. doi: 10.7326/m14-2385CrossRefGoogle Scholar
Jakobsen, J. C., Katakam, K. K., Schou, A., Hellmuth, S. G., Stallknecht, S. E., Leth-Møller, K., … Gluud, C. (2017). Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis. BMC Psychiatry, 17(1), 58. doi: 10.1186/s12888-016-1173-2CrossRefGoogle ScholarPubMed
Jang, H. M., Lee, H. J., Jang, S. E., Han, M. J., & Kim, D. H. (2018a). Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice. Mucosal Immunology, 11(5), 1386–1397. doi: 10.1038/s41385-018-0042-3CrossRefGoogle ScholarPubMed
Jang, H. M., Lee, K. E., & Kim, D. H. (2019). The preventive and curative effects of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 on immobilization stress-induced anxiety/depression and colitis in mice. Nutrients, 11(4), 819. doi: 10.3390/nu11040819CrossRefGoogle Scholar
Jang, S. E., Lim, S. M., Jeong, J. J., Jang, H. M., Lee, H. J., Han, M. J., & Kim, D. H. (2018b). Gastrointestinal inflammation by gut microbiota disturbance induces memory impairment in mice. Mucosal Immunology, 11(2), 369–379. doi: 10.1038/mi.2017.49CrossRefGoogle ScholarPubMed
Kessler, R. C., Petukhova, M., Sampson, N. A., Zaslavsky, A. M., & Wittchen, H. U. (2012). Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research, 21(3), 169–184. doi: 10.1002/mpr.1359CrossRefGoogle Scholar
Khin, N. A., Chen, Y. F., Yang, Y., Yang, P., & Laughren, T. P. (2011). Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US food and drug administration in support of new drug applications. Journal of Clinical Psychiatry, 72(4), 464–472. doi: 10.4088/JCP.10m06191CrossRefGoogle Scholar
Kwoji, I. D., Aiyegoro, O. A., Okpeku, M., & Adeleke, M. A. (2021). Multi-strain probiotics: Synergy among isolates enhances biological activities. Biology-Basel, 10(4), 322. doi: 10.3390/biology10040322CrossRefGoogle ScholarPubMed
LeBlanc, J. G., Chain, F., Martín, R., Bermúdez-Humarán, L. G., Courau, S., & Langella, P. (2017). Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microbial Cell Factories, 16(1), 79. doi: 10.1186/s12934-017-0691-zCrossRefGoogle ScholarPubMed
Liu, Y. W., Liu, W. H., Wu, C. C., Juan, Y. C., Wu, Y. C., Tsai, H. P., … Tsai, Y. C. (2016). Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain Research, 1631, 1–12. doi: 10.1016/j.brainres.2015.11.018CrossRefGoogle ScholarPubMed
Macaskill, P., Walter, S. D., & Irwig, L. (2001). A comparison of methods to detect publication bias in meta-analysis. Statistics in Medicine, 20(4), 641–654. doi: 10.1002/sim.698CrossRefGoogle ScholarPubMed
Maes, M. (2001). The immunoregulatory effects of antidepressants. Human Psychopharmacology-Clinical And Experimental, 16(1), 95–103. doi: 10.1002/hup.191CrossRefGoogle ScholarPubMed
Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., … Cazaubiel, J. M. (2011). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition, 105(5), 755–764. doi: 10.1017/s0007114510004319CrossRefGoogle Scholar
Molina-Torres, G., Rodriguez-Arrastia, M., Roman, P., Sanchez-Labraca, N., & Cardona, D. (2019). Stress and the gut microbiota-brain axis. Behavioural Pharmacology, 30(2 and 3-Spec Issue), 187–200. doi: 10.1097/fbp.0000000000000478CrossRefGoogle Scholar
Musazadeh, V., Zarezadeh, M., Faghfouri, A. H., Keramati, M., Jamilian, P., Jamilian, P., … Farnam, A. (2023). Probiotics as an effective therapeutic approach in alleviating depression symptoms: An umbrella meta-analysis. Critical Reviews in Food Science And Nutrition, 63(26), 8292–8300. doi: 10.1080/10408398.2022.2051164CrossRefGoogle Scholar
Naseribafrouei, A., Hestad, K., Avershina, E., Sekelja, M., Linløkken, A., Wilson, R., & Rudi, K. (2014). Correlation between the human fecal microbiota and depression. Neurogastroenterology And Motility, 26(8), 1155–1162. doi: 10.1111/nmo.12378CrossRefGoogle ScholarPubMed
Nishiyama, K., Sugiyama, M., & Mukai, T. (2016). Adhesion properties of lactic acid bacteria on intestinal mucin. Microorganisms, 4(3), 34. doi: 10.3390/microorganisms4030034CrossRefGoogle ScholarPubMed
Plaza-Diaz, J., Ruiz-Ojeda, F. J., Gil-Campos, M., & Gil, A. (2019). Mechanisms of action of probiotics. Advances In Nutrition, 10(suppl_1), S49–s66. doi: 10.1093/advances/nmy063CrossRefGoogle ScholarPubMed
Rhoads, J. M., Collins, J., Fatheree, N. Y., Hashmi, S. S., Taylor, C. M., Luo, M., … Liu, Y. (2018). Infant colic represents Gut inflammation and dysbiosis. Journal of Pediatrics, 203, 55–61. doi: 10.1016/j.jpeds.2018.07.042CrossRefGoogle ScholarPubMed
Rudzki, L., Ostrowska, L., Pawlak, D., Małus, A., Pawlak, K., Waszkiewicz, N., & Szulc, A. (2019). Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology, 100, 213–222. doi: 10.1016/j.psyneuen.2018.10.010CrossRefGoogle ScholarPubMed
Salanti, G., Ades, A. E., & Ioannidis, J. P. (2011). Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial. Journal of Clinical Epidemiology, 64(2), 163–171. doi: 10.1016/j.jclinepi.2010.03.016CrossRefGoogle Scholar
Simpson, C. A., Diaz-Arteche, C., Eliby, D., Schwartz, O. S., Simmons, J. G., & Cowan, C. S. M. (2021). The gut microbiota in anxiety and depression – A systematic review. Clinical Psychology Review, 83, 101943. doi: 10.1016/j.cpr.2020.101943CrossRefGoogle ScholarPubMed
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., … Koga, Y. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology-London, 558(Pt 1), 263–275. doi: 10.1113/jphysiol.2004.063388CrossRefGoogle ScholarPubMed
Thase, M. E., Weisler, R. H., Manning, J. S., & Trivedi, M. H. (2017). Utilizing the DSM-5 anxious distress specifier to develop treatment strategies for patients with major depressive disorder. Journal of Clinical Psychiatry, 78(9), 22046.Google Scholar
Tsukuda, N., Yahagi, K., Hara, T., Watanabe, Y., Matsumoto, H., Mori, H., … Matsuki, T. (2021). Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life. Isme Journal, 15(9), 2574–2590. doi: 10.1038/s41396-021-00937-7CrossRefGoogle Scholar
Turroni, F., Ventura, M., Buttó, L. F., Duranti, S., O'Toole, P. W., Motherway, M. O., & van Sinderen, D. (2014). Molecular dialogue between the human gut microbiota and the host: A Lactobacillus and Bifidobacterium perspective. Cellular And Molecular Life Sciences, 71(2), 183–203. doi: 10.1007/s00018-013-1318-0CrossRefGoogle Scholar
Vaghef-Mehrabany, E., Maleki, V., Behrooz, M., Ranjbar, F., & Ebrahimi-Mameghani, M. (2020). Can psychobiotics “mood” ify gut? An update systematic review of randomized controlled trials in healthy and clinical subjects, on anti-depressant effects of probiotics, prebiotics, and synbiotics. Clinical Nutrition, 39(5), 1395–1410. doi: 10.1016/j.clnu.2019.06.004CrossRefGoogle Scholar
Veroniki, A. A., Vasiliadis, H. S., Higgins, J. P., & Salanti, G. (2013). Evaluation of inconsistency in networks of interventions. International Journal of Epidemiology, 42(1), 332–345. doi: 10.1093/ije/dys222CrossRefGoogle ScholarPubMed
World Health Organization. (2022, March 2) Mental Health and COVID-19: Early evidence of the pandemic's impact. Retrieved from: https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Mental_health-2022.1Google Scholar
Zhang, J., Li, L., Liu, Q., Zhao, Z., Su, D., Xiao, C., … Zhou, T. (2023). Gastrodin programs an Arg-1(+) microglial phenotype in hippocampus to ameliorate depression- and anxiety-like behaviors via the Nrf2 pathway in mice. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 113, 154725. doi: 10.1016/j.phymed.2023.154725CrossRefGoogle ScholarPubMed
Zmora, N., Zilberman-Schapira, G., Suez, J., Mor, U., Dori-Bachash, M., Bashiardes, S., … Elinav, E. (2018). Personalized gut mucosal colonization resistance to empiric probiotics Is associated with unique host and microbiome features. Cell, 174(6), 1388–1405. e1321. doi: 10.1016/j.cell.2018.08.041CrossRefGoogle ScholarPubMed
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