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The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature
Open accessAbstract
BACKGROUND: Probiotics have generated intensive research interest in recent years as a novel mode of treatment for physical and mental illness. Nevertheless, the anxiolytic potential of probiotics remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety. METHODS: The PubMed, PsycINFO, and Web of Science databases were reviewed for preclinical and clinical studies that met the defined inclusion and exclusion criteria. The effects of probiotics on anxiety-like behavior and symptoms of anxiety were analyzed by meta-analyses. Separate subgroup analyses were conducted on diseased versus healthy animals, specific preclinical probiotic species, and clinical versus healthy human samples. RESULTS: Data were extracted from 22 preclinical studies (743 animals) and 14 clinical studies (1527 individuals). Overall, probiotics reduced anxiety-like behavior in animals (Hedges' g = -0.47, 95% CI -0.77 --0.16, p = 0.004). Subgroup analyses revealed a significant reduction only among diseased animals. Probiotic species-level analyses identified only Lactobacillus (L.) rhamnosus as an anxiolytic species, but these analyses were broadly under-powered. Probiotics did not significantly reduce symptoms of anxiety in humans (Hedges' g = -0.12, 95% CI -0.29-0.05, p = 0.151), and did not differentially affect clinical and healthy human samples. CONCLUSIONS: While preclinical (animal) studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans, perhaps due to the dearth of extant research with clinically anxious populations. Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.
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“More recently, a systematic review and meta-analysis of clinical and pre-clinical literature on the effects of probiotics on anxiety asserted that probiotics may help reduce anxiety [297].”
From International Society of Sports Nutrition Position Stand: Probiotics (2019) · cites this paper as [297]
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“Furthermore, probiotic supplementations, as Lactobacillus rhamnosus (JB-1), in already colonized mice, reduced anxiety- and depression-like behavior in steady-state conditions (92, 93).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [92]
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000100 · Cited by 28,164
Dermyshi, E., Wang, Y., Yan, C., Hong, W., Qiu, G., Gong, X., & Zhang, T. (2017) · Neonatology · doi:10.1159/000454668 · Cited by 24,586
Sterne, J. A. C., Sutton, A. J., Ioannidis, J. P. A., Terrin, N., Jones, D. R., Lau, J., Carpenter, J., Rucker, G., Harbord, R. M., Schmid, C. H., et al. (2011) · BMJ · doi:10.1136/bmj.d4002 · Cited by 7,709
Power failure: why small sample size undermines the reliability of neuroscience
Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3475 · Cited by 7,641
Changes of Intestinal Functions in Liver Cirrhosis
Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533
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Enck, P., & Mazurak, N. (2019) · Zeitschrift für Gastroenterologie · doi:10.1055/a-0901-2558 · Cited by 1
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Borghi, E., Vignoli, A., & D’Agostino, A. (2019) · Behavioral and Brain Sciences · doi:10.1017/s0140525x18002844 · Cited by 1
Myakotnykh, V. S., Анохина, М. В., Sidenkova, A. P., Serdyuk, O., & Мельник, А. А. (2020) · Сибирский вестник психиатрии и наркологии · doi:10.26617/1810-3111-2020-4(109)-73-81 · Cited by 2
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Farahmandi, K., Sulaimany, S., & Kalhor, K. (2021) · medRxiv · doi:10.1101/2021.08.23.21262411 · Cited by 1
Computational psychiatry 2.0 and implications for stress researchPreprint
Pashkov, A. A., & Беребин, М. А. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/483164
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Brzezicki, M. A., Celentano, L., Ostrowski, M., & Chakraborty, A. (2020) · Clinical Neuropsychopharmacology and Therapeutics · doi:10.5234/cnpt.11.67
Impact of early nutrition on gut microbiota: Effects on immunity and long-term health
Laitinen, K., Mokkala, K., & Kalliomäki, M. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824389-3.00005-2
Grace, S., Bradbury, J., Avila, C., Twohill, L., & Morgan-Basnett, S. (2023) · Journal of Integrative and Complementary Medicine · doi:10.1089/jicm.2022.0820
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Supplements Effective in the Treatment of Mental Health Conditions
Hayek, S. E., Koukach, N., Tolba, H., & Foad, W. (2024) · Nutritional neurosciences · doi:10.1007/978-981-97-2681-3_18
Machaca-Luque, L. Y., Candia-Puma, M. A., Roque-Pumahuanca, B. M., Barazorda-Ccahuana, H. L., Goyzueta-Mamani, L. D., Galdino, A. S., Machado‐de‐Ávila, R. A., Giunchetti, R. C., Coelho, E. A. F., & Chávez‐Fumagalli, M. Á. (2024) · F1000Research · doi:10.12688/f1000research.150723.1
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Cotta, M. L. C., & Galarza, K. B. (2025) · South Health and Policy · doi:10.56294/shp2025199
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Przerwa, J. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.4(48).2025.4431 · Cited by 1
Yu, S., Hong, P., Chou, S., Liang, T.-F., Lin, K.-S., Lai, C.-H., & Wang, C.-M. (2026) · BMC Microbiology · doi:10.1186/s12866-026-04935-7
Herkes, S., Lukaszuk, J. M., Walker, D. A., Shokrani, M., & Stark, M. (2026) · Journal of Medicinal Food · doi:10.1177/1096620x261421081
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Jose, J., Devassy, S. M., Ravi, A., Saidumohamed, B. E., Pramod, A. V., Benny, I. J., Pereira, M. D. L., & Anjos, M. (2026) · Nutritional Neuroscience · doi:10.1080/1028415x.2026.2747374
Metadata
- Authors
- Reis, D. J., Ilardi, S. S., & Punt, S. E. W.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Reis, Daniel J.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-06-20
- Volume
- 13
- Issue
- 6
- Pages
- e0199041
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6010276
- OpenAlex
- W2809387633
- Cited by
- 123
- References
- 100
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 19 · 2023: 18 · 2022: 13 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- KU ScholarWorks (University of Kansas) (submittedVersion, cc-by)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- probiotics, anxiety, anxiolytic effects, anxiety-like behavior, Lactobacillus rhamnosus, clinical anxiety, animal models of anxiety, gut microbiota, translational research
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Drug Evaluation, Preclinical, Exploratory Behavior, Female, Humans, Male, Research Design, Species Specificity, Anti-Anxiety Agents, Randomized Controlled Trials as Topic, Maze Learning, Probiotics, Mice, Rats, Lacticaseibacillus rhamnosus
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