Review articleA meta-analysis of the use of probiotics to alleviate depressive symptoms
Introduction
Depression is a growing public health concern. The World Health Organization currently estimates that depression affects over 350 million people worldwide and accounts for approximately 7.5% of healthy years lost due to disability (WHO, 2017). The immense physical, mental and socio-economic repercussions of depression make it a key area of research focus and emphasize the need for novel treatment strategies. Despite ongoing efforts to discover new anti-depressants, selective serotonin reuptake inhibitors (SSRIs) have remained the mainstay of medical management for more than 20 years. Various concerns have however been raised regarding the efficacy and tolerability of SSRIs. Results from several large scale meta-analyses (Jakobsen et al., 2017, Khin et al., 2011, Kirsch et al., 2008) have called into question the clinical significance of SSRIs over placebo, with SSRIs bearing the additional risk of serious adverse events (Ferguson, 2001). Furthermore, compliance with current anti-depressants is decidedly poor with less than 50% of patients demonstrating adequate adherence within a 6-month period (Keene et al., 2005). Given the many challenges that plague the use of SSRIs, innovative treatment modalities to combat depression are necessary to improve patient care.
In recent years, probiotics have garnered significant attention for their wide array of clinical uses, ranging from gastrointestinal (GI) disorders to autoimmune illnesses and skin conditions (Zuccotti et al., 2008). Various studies have explored the link between gut microflora and mood disorders, investigating the role of the gut-brain axis in the pathophysiology of depression. It is theorized that intestinal bacteria play a major role in the bidirectional signaling between the brain and the gut, by which emotional affect influences GI function while GI health alters brain function (Schmidt, 2015). Disruption of the gut-brain axis is therefore associated with both physical and neurological ailments. Moreover, relatively new research has outlined the role of immune dysregulation as part of the pathogenesis of depression (Leonard, 2010). As such, the well documented anti-inflammatory and immune-regulatory properties of probiotics (Isolauri et al., 2001) offer hope for tackling one of the underlying causes of depression with the aim of inducing long-term remission. Preclinical trials in animal models have found that probiotic consumption downregulates the hypothalamic–pituitary–adrenal (HPA) axis (thought to be overactive in depression) (Ait-Belgnaoui et al., 2014), promotes biosynthesis of GABA (known to be reduced in depressed patients) (Dhakal et al., 2012) and boosts serotonin levels through increased production of tryptophan, a serotonin precursor (Desbonnet et al., 2008).
With increasing evidence on the benefits of probiotics in a host of diseases, there has been a surge in the number of clinical trials examining their application in mental health illnesses such as depression. Results from a previous meta-analysis have indicated that probiotic formulations do have a positive psychological impact (Huang et al., 2016) and may offer a paradigm shift in the treatment of depression as either an adjunct to standard therapy or as a stand-alone treatment. This paper aims to provide an updated meta-analysis on the topic and outline directions for future research.
Section snippets
Patient involvement
This article does not contain any studies with human participants performed by any of the authors. Patients/service users/carers/lay people were not involved in the design or course of this study.
Search strategy
Literature search was done in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the keywords [probiotics OR gut OR microflora OR microbiome OR bacteria OR yeast OR yoghurt OR lactobacillus OR bifidobacterium] AND [mood OR depression OR MDD OR
Results
The abstraction process was illustrated in Fig. 1. The key details of each study were extracted and summarized in Table 1. Two studies were excluded from the meta-analysis as the data were not reported as mean ± standard deviation and the raw data were unavailable.
These studies were randomized, placebo-controlled, double-blind trials with a generally low risk of bias (Table 2).
With regard to the possibility of publication bias, visual inspection of the funnel plot revealed a largely symmetrical
Discussion
Current evidence suggests that although the overall effect of probiotics is statistically insignificant for a combined data set of both depressed and healthy individuals (SMD −0.128, 95% CI −0.261 to 0.00463, P=0.059), a statistically significant benefit is seen in mild to moderately depressed patients (SMD −0.684, 95% CI −1.296 to −0.0712, P=0.029). Unlike SSRIs however, probiotics are well-tolerated with no adverse events reported by the 1349 patients collectively enrolled in the ten included
Conclusion
A meta-analysis of 10 randomized controlled trials found that probiotic supplementation had overall insignificant effects on mood (SMD=−0.128, 95% CI −0.261 to 0.00463, P=0.059). Subgroup analyses found modest effects in individuals with pre-existing mood symptoms, while the effects tended to be insignificant in healthy, community-dwelling individuals. Although generally safe and palatable, it cannot be recommended that probiotics replace anti-depressant medications as the primary treatment for
Acknowledgements
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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