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

Date Published: June 20, 2018

Publisher: Public Library of Science

Author(s): Daniel J. Reis, Stephen S. Ilardi, Stephanie E. W. Punt, Jane Foster.


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.

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.

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.

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.

Partial Text

Anxiety disorders are a class of psychological disturbances characterized by pervasive worry, fear, and related behavioral impairments. Collectively, they are the most prevalent form of mental illness [1]—affecting up to 30% of American adults at some point—and they impose a large societal burden of functional disability and mortality [2]. Excessive anxiety is also associated with numerous negative health outcomes, such as increased risk of coronary heart disease [3], impaired sleep [4], and alcohol and substance abuse [5]. Although there now exist several established medication- and psychotherapy-based treatments for anxiety [6], many patients still experience a poor treatment response [7, 8]. The widespread and debilitating nature of anxiety, in tandem with the frequent inadequacy of existing treatments, points to the desirability of exploring and developing novel approaches to treatment.

The preclinical and clinical reviews followed CAMARADES and PRISMA guidelines for conducting systematic reviews and meta-analyses, respectively [30, 31]. The study was not preregistered, and the protocol can be viewed at Inclusion and exclusion criteria were selected to maximize the acquisition of all possible studies that examined the effects of probiotic administration on anxiety-like behavior in rodents or symptoms of anxiety in humans. Conference abstracts were omitted due to a lack of necessary information.

The present systematic review and meta-analysis of 22 preclinical studies (743 animals) revealed a significant overall effect of probiotic administration in reducing anxiety-like behavior in rodents. The observed pooled standardized mean difference (SMD) of -0.47 reflects a medium-sized effect of probiotic interventions in comparison with non-probiotic controls. At the level of individual trials, 12 of the 22 included animal studies found that probiotics significantly reduced anxiety-like behavior on at least one outcome measure, with the remaining 10 studies finding either no effect or (in one case) increased anxiety-like behavior.




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