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Cited by 123Probiotics and Fermented FoodsMedicinal Plant Extracts EffectsGastrointestinal motility and disorders

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The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature

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Reis, Daniel J., Ilardi, Stephen S., Punt, Stephanie E. W.·2018·PLOS ONE
DOI 10.1371/journal.pone.0199041PMC PMC6010276
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Abstract

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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Fig 1 Flow and selection of preclinical studies.
Fig 1 Flow and selection of preclinical studies.CC BY · PubMed Central
Fig 2 Flow and selection of clinical studies.
Fig 2 Flow and selection of clinical studies.CC BY · PubMed Central
Fig 3 Forest plot of preclinical studies investigating the effect of probiotics on anxiety-like behavior. SMD = Standardized mean difference; CI = Confidence interval. An aggregate SMD is displayed for each experimental group. Measure-specific SMDs can be viewed in S1 Fig.
Fig 3 Forest plot of preclinical studies investigating the effect of probiotics on anxiety-like behavior. SMD = Standardized mean difference; CI = Confidence interval. An aggregate SMD is displayed for each experimental group. Measure-specific SMDs can be viewed in S1 Fig.CC BY · PubMed Central
Fig 4 Funnel plot of preclinical standardized mean differences.
Fig 4 Funnel plot of preclinical standardized mean differences.CC BY · PubMed Central
Fig 5 Forest plot of clinical studies investigating the effect of probiotics on anxiety-like behavior. SMD = Standardized mean difference; CI = Confidence interval; STAI = State-Trait Anxiety Inventory; BAI = Beck Anxiety Inventory; VSI = Visceral Sensitivity Index; HADS = Hospital Anxiety and Depression Scale; HSCL-90 = Hopkins Symptom Checklist-90; DASS = Depression Anxiety Stress Scales; HAM-A = Hamilton Anxiety Rating Scale.
Fig 5 Forest plot of clinical studies investigating the effect of probiotics on anxiety-like behavior. SMD = Standardized mean difference; CI = Confidence interval; STAI = State-Trait Anxiety Inventory; BAI = Beck Anxiety Inventory; VSI = Visceral Sensitivity Index; HADS = Hospital Anxiety and Depression Scale; HSCL-90 = Hopkins Symptom Checklist-90; DASS = Depression Anxiety Stress Scales; HAM-A = Hamilton Anxiety Rating Scale.CC BY · PubMed Central
Fig 6 Funnel plot of clinical standardized mean differences.
Fig 6 Funnel plot of clinical standardized mean differences.CC BY · PubMed Central

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Metadata

Authors
Reis, D. J., Ilardi, S. S., & Punt, S. E. W.
Affiliations
University of Kansas (US)
Corresponding author
Reis, Daniel J.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-06-20
Volume
13
Issue
6
Pages
e0199041
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0199041
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
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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