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

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.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

Forest plot of preclinical studies investigating the effect of probiotics on anxiety-like behavior.

<p>SMD = Standardized mean difference; CI = Confidence interval. An aggregate SMD is displayed for each experimental group. Measure-specific SMDs can be viewed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199041#pone.0199041.s003" target="_blank">S1 Fig</a>.</p

Preclinical risk of bias assessment.

<p>Preclinical risk of bias assessment.</p

Clinical risk of bias assessment.

<p>Clinical risk of bias assessment.</p

Funnel plot of preclinical standardized mean differences.

<p>Funnel plot of preclinical standardized mean differences.</p

Clinical study characteristics.

<p>Clinical study characteristics.</p

Funnel plot of clinical standardized mean differences.

<p>Funnel plot of clinical standardized mean differences.</p

Flow and selection of preclinical studies.

<p>Flow and selection of preclinical studies.</p

Forest plot of clinical studies investigating the effect of probiotics on anxiety-like behavior.

<p>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.</p