Experimental research has previously shown how the gut microbiota is involved in regulating brain function through the gut-brain axis. Depression and anxiety are among the most prevalent mental health conditions in industrialized countries and there is a current need for novel psychopharmacological medications to be developed for both conditions. Although the gut microbiota has been hypothesized to be involved in the development of depression and anxiety, the extent to which targeting it might be used as a potential treatment for both conditions has yet to be clarified.

A new systematic review and meta-analysis of 34 controlled clinical trials, led by researchers from the Department of Psychiatry and Human Behavior at the Warren Alpert Medical School at Brown University (Rhode Island, USA), concludes that probiotics may exert potential antidepressant and anxiolytic effects.

The authors acknowledged that previous systematic reviews of probiotics for managing depression and anxiety have been published. However, they were not exempt from limitations such as including a low number of studies and having evidence of publication bias and methodological biases (e.g. mixing depression and anxiety as a single outcome).

The meta-analysis considered 34 controlled clinical trials, of which 7 consisted of prebiotic interventions while 27 were probiotic or symbiotic interventions.

The administration of prebiotics—including galactooligosaccharides (GOS), fructooligosaccharides (FOS) and short-chain FOS—from 4 hours to 4 weeks did not lead to any difference from placebo for depression or anxiety.

Within 23 trials looking at probiotic effects on depression and 22 trials looking at probiotic effects on anxiety, the administration of probiotics—including Bifidobacterium longum, Bacillus coagulans, and Lactobacillus alone or in combination with Bifidobacteriumfrom 8 to 45 weeks led to small but significant antidepressant and antianxiety effects.

Stronger effects were observed in studies using small clinical samples, including individuals with major depressive symptoms (4 trials). In contrast, the meta-analysis did not observe any benefits in using probiotics to manage depression and anxiety in studies with healthy community samples, which were indeed the most abundant in the literature.

It should be acknowledged that the most frequently used probiotics containing Lactobacillus, when used alone did not show an effect on depression or anxiety. A significant effect was only observed when Lactobacillus was combined with another genera.

On the whole, the authors explained that the relative scarcity of trials using psychiatric samples and the prevalence of non-clinical samples in the assessed studies contribute to explaining the modest effects of probiotics on depression and anxiety when considered together as a category.

Regarding study quality assessment using Cochrane criteria, only 26% had an overall low risk of bias, while 41% of trials reported had a high risk of bias for at least one criterion being violated, while for the remaining 33%, risk assessment was not possible due to incomplete data reporting.

In conclusion, the findings of controlled clinical trials included in this meta-analysis suggest a potential antidepressant and anxiolytic role for probiotics, whereas prebiotics do not differ from placebo. Taking into account the addictive properties of some medical treatments for anxiety and depression and given that probiotics have been reported to be free of central and other side effects, the findings of this meta-analysis suggest that probiotics could be a promising therapeutic tool when managing depression and anxiety.



Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019; 102:13-23. doi: 10.1016/j.neubiorev.2019.03.023.