Elsevier

Journal of Affective Disorders

Volume 228, 1 March 2018, Pages 13-19
Journal of Affective Disorders

Review article
A meta-analysis of the use of probiotics to alleviate depressive symptoms

https://doi.org/10.1016/j.jad.2017.11.063Get rights and content

Highlights

  • 10 randomized, controlled trials with a total of 1349 patients were reviewed.

  • The use of probiotics was compared to placebo controls.

  • Probiotic supplementation has an overall insignificant effect on mood.

  • Future studies should be conducted on more patients with clinically diagnosed MDD.

Abstract

Introduction

Some preclinical and clinical studies have demonstrated the positive impact of probiotic supplementation on depressive symptoms. This paper aims to provide an updated meta-analysis on the topic.

Methods

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 suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR) and Cochrane Field for Complementary Medicine database yielded 917 papers published in English between 1-Jan-1960 and 1-June-2017.

Results

10 clinical trials with a total of 1349 patients were reviewed, comparing the use of probiotics to placebo controls. There was no significant difference in mood between the treatment and placebo group post-intervention as the standardized mean difference (SMD) was −0.128 (95% CI −0.261 to 0.00463, P=0.059). A separate subgroup analysis of studies conducted in healthy versus depressed individuals found significant improvements in the moods of individuals with mild to moderate depressive symptoms (SMD −0.684, 95% CI −1.296 to −0.0712, P=0.029) and non-significant effects in healthy individuals (SMD −0.0999, 95% CI −0.235 to 0.0348, P=0.146).

Limitations

Inter-study discrepancies with respect to probiotic dosing, bacterial strains and strain combinations limit the comparability of current clinical trials. Furthermore, majority of existing RCTs were conducted in healthy individuals, making it difficult to extrapolate the results to depressed individuals.

Conclusion

Probiotic supplementation has an overall insignificant effect on mood. Future studies should be conducted on more patients with clinically diagnosed depression.

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.

References (45)

  • E. Roueche et al.

    Influence of temperature on the compaction of an organic powder and the mechanical strength of tablets

    Powder Technol.

    (2006)
  • L. Steenbergen et al.

    A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood

    Brain Behav. Immun.

    (2015)
  • J.M. Yano et al.

    Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis

    Cell

    (2015)
  • A. Ait-Belgnaoui et al.

    Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice

    Neurogastroenterol. Motil.

    (2014)
  • E. Barrett et al.

    gamma-Aminobutyric acid production by culturable bacteria from the human intestine

    J. Appl. Microbiol.

    (2012)
  • D. Benton et al.

    Impact of consuming a milk drink containing a probiotic on mood and cognition

    Eur. J. Clin. Nutr.

    (2007)
  • P. Bercik et al.

    The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication

    Neurogastroenterol. Motil.

    (2011)
  • P. Blier et al.

    Preventing recurrent depression: long-term treatment for major depressive disorder

    J. Clin. Psychiatry

    (2007)
  • P.A. Bolla et al.

    Effect of freeze-drying on viability and in vitro probiotic properties of a mixture of lactic acid bacteria and yeasts isolated from kefir

    J. Dairy Res.

    (2011)
  • M. Carabotti et al.

    The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

    Ann. Gastroenterol.

    (2015)
  • R. Dhakal et al.

    Production of gaba (gamma - Aminobutyric acid) by microorganisms: a review

    Braz. J. Microbiol.

    (2012)
  • J.M. Ferguson

    SSRI antidepressant medications: adverse effects and tolerability

    Prim. Care Companion J. Clin. Psychiatry

    (2001)
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