Journal of Affective Disorders 228 (2018) 13–19
Contents lists available at ScienceDirect
Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad
Review article
A meta-analysis of the use of probiotics to alleviate depressive symptoms
a,⁎
b
c
d
Qin Xiang Ng , Christina Peters , Collin Yih Xian Ho , Donovan Yutong Lim , Wee-Song Yeo
T
c,e
a
KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore
University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom
National University Hospital, National University Health System, Singapore 119074, Singapore
d
Department of Child and Adolescent Psychiatry, Institute of Mental Health, 10 Buangkok View, Singapore 539747, Singapore
e
Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
b
c
A R T I C L E I N F O
A B S T R A C T
Keywords:
Mood
Depression
MDD
Probiotics
Lactobacillus
Gut-brain axis
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.
1. 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 6month 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-
Corresponding author.
E-mail address: ng.qin.xiang@u.nus.edu (Q.X. Ng).
https://doi.org/10.1016/j.jad.2017.11.063
Received 18 July 2017; Received in revised form 15 September 2017; Accepted 13 November 2017
Available online 16 November 2017
0165-0327/ © 2017 Elsevier B.V. All rights reserved.
Journal of Affective Disorders 228 (2018) 13–19
Q.X. Ng et al.
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.
2. Methods
Fig. 1. PRISMA flowchart showing the studies identified during the literature search and
abstraction process.
2.1. Patient involvement
Depression Scale (HADS), or Beck Depression Inventory (BDI) from
baseline with treatment. Estimates were pooled and where appropriate,
95% confidence intervals (95% CI) and P-values were calculated.
Heterogeneity amongst the different studies pooled was examined
using the I2 statistic and Cochran's Q test. If heterogeneity was small (I2
≤50%), a fixed effects model was applied for the meta-analysis.
Publication bias was assessed using a funnel plot and Egger test. All
analyses were done using MedCalc Statistical Software version 14.8.1
(MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org;
2014).
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.
2.2. 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 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.
Grey literature was not searched. Title/abstract screening were performed independently by the researchers (QX Ng, C Peters and CYX Ho)
to identify articles of interest. For relevant abstracts, full articles were
obtained, reviewed and also checked for references of interest. The
authors of the articles were not contacted to provide additional data.
Full articles were obtained for all selected abstracts and reviewed by
three researchers (QX Ng, C Peters and CYX Ho) for inclusion. Any
disagreement was resolved by discussion and consensus amongst the
three researchers. The inclusion criteria for this review were: (1) published randomized controlled trial, (2) specified dose of probiotic was
administered as an active intervention, and (3) mood symptoms were
quantified using a validated rating scale e.g. Hospital Anxiety and
Depression Scale (HADS), or Beck Depression Inventory (BDI) pre- and
post-intervention.
Methodological quality of the eligible clinical trials was appraised
using the Jadad scale (Jadad et al., 1996) by all investigators (consensus), and the Cochrane Collaboration's tool for assessing risk of bias
(Higgins et al., 2011) of randomized controlled trials was also applied.
Data such as study design, study population and demographics and
outcome measures were extracted. The primary outcome measures of
interest were treatment response and safety/incidence of adverse effects. Treatment response was quantified using Cohen's d, standardized
mean difference (SMD) for mean reduction in depressive symptoms, as
quantified using a validated rating scale e.g. Hospital Anxiety and
3. 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 distribution of studies
(Fig. 2) and Egger test was not significant for publication bias
(P=0.5495). Thus, the likelihood of publication bias is small.
A sensitivity analysis was not conducted given the rigorous methodological quality of all available trials as well as the small number of
available trials).
As seen in Fig. 3, there was no significant difference in mood
symptoms between the treatment and placebo group post-intervention
as the SMD (Cohen's d) was −0.128 (95% CI −0.261 to 0.00463,
P=0.059). A separate subgroup analysis of studies conducted in
healthy individuals (Fig. 4) versus those conducted in individuals with
MDD or mild to moderate anxiety and/or depression (Fig. 5) was
conducted as well. It was found that probiotic supplementation produced significant improvements in the moods of individuals with mildmoderate depressive symptoms (SMD=−0.684, 95% CI −1.296 to
−0.0712, P=0.029), but had non-statistically significant effects in
healthy individuals (SMD=−0.0999, 95% CI −0.235 to 0.0348,
P=0.146), perhaps owing to the generally good baseline mood of many
healthy individuals in the sample. This is concordant with the
14
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
double-blind trial
Akkasheh et al.
(2016)
Benton et al.
(2007)
Chung et al.
(2014)
Freeze-dried Lactobacillus
acidophilus (2 × 109 CFU/
g), Lactobacillus casei (2 ×
109 CFU/g), and
Bifidobacterium bifidum (2 ×
109 CFU/g) for 8 weeks
Milk drink containing L.
casei Shirota (6.5 × 109
CFU/g) for 3 weeks
N=40, patients with MDD, Age 20–55 years
Yoghurt (100 g/day)
containing L. gasseri
SBT2055 and B. longum
SBT2928 (1.5 × 109 CFU/g)
for 12 weeks
N=224, healthy Japanese adults, Age 32–76 years
15
N=44, patients with irritable bowel syndrome (IBS) and mild to moderate
anxiety and/or depression, Age 26–58 years
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebo-
ÖstlundLagerström
et al. (2016)
Rao et al. (2009)
N=39, patients with chronic fatigue syndrome (CFS), Age 18–65 years
Spray-dried B. longum
NCC3001 (1 × 1010 CFU/g
powder with maltodextrin)
for 10 weeks
N=290, healthy older adults, Age > 65 years
Randomized,
placebocontrolled,
double-blind trial
Mohammadi
et al. (2016)
Pinto-Sanchez
et al. (2017)
Yoghurt (100 g/day)
containing L. acidophilus and
B. lactis (1 × 107 CFU/g) OR
multispecies probiotic
capsule containing
Actobacillus casei (3 × 103),
L. acidophilus (3 × 107), L.
rhamnosus (7 × 109), L.
bulgaricus (5 × 108), B. breve
(2 × 1010), B. longum (1 ×
109) and Streptococcus
thermophilus (3 × 108 CFU/
g) for 6 weeks
Freeze-dried L. reuteri DSM
17938 (1 × 108 CFU/g) for
12 weeks
N=70, healthy petrochemical workers, Age 20–60 years
Randomized,
placebocontrolled,
double-blind trial
N=55, healthy Caucasian individuals, Mean age 43 years
Tablet containing 125, 250
and 500 mg of L. helveticus
IDCC3801 and appropriate
excipients for 12 weeks
L. helveticus R0052 and B.
longum R0175 (3 × 109
CFU/g) for 30 days
N=36, healthy older adults, Mean age 65 years ± 4.14 (std dev)
N=132, healthy individuals, Mean age 61.8 years
Probiotic dosage and
duration
Study sample
Nishihara et al.
(2014)
Messaoudi et al.
(2011)
Study design
Author, year
Table 1
Characteristics of all studies included in this meta-analysis (arranged alphabetically by first Author's last name).
Formal
diagnosis
Rome III
criteria;
HADS score
8–14
NA
NA
NA
BDI, BAI, stool
analysis
HADS, STAI,
Birmingham IBS
symptom score
GSRS, HADS,
PSS, EQ-5D-5L
GHQ-28, DASS
and fasting
blood samples
GHQ-28, serum
levels of ACTH
and cortisol
HSCL-90, HADS,
PSS, CCL and
24 h urinary free
cortisol
PSS, GDS-SF,
BDNF
NA
NA
POMS, self-rated
mood
BDI
Outcome
measures
NA
DSM-IV
Diagnosis
criteria
4
5
Canada
Canada
5
5
4
5
5
4
5
Jadad
Scale
Sweden
Iran
Japan
France
Korea
United
Kingdom
Iran
Country of
origin
Probiotic consumption
reduces depression but not
anxiety scores and increases
quality of life in patients with
IBS.
Probiotic consumption had
significant improvement in
(continued on next page)
No persistent significant
effects on wellbeing, anxiety
or stress were observed.
Consumption of probioticcontaining yoghurt only
improved self-reported mood
of those whose mood was
initially poor.
Improvements in cognitive
testing but no significant
effects on PSS, GDS-SF, and
BDNF.
Probiotic consumption
improved HADS global score,
the global severity index of
the HSCL-90 and three of its
sub-scores (somatization,
depression and angerhostility).
Although serum ACTH levels
were significantly decreased
by the test yoghurt, no
significant differences in
GHQ-28 score were observed
between the test and placebo
groups.
Consumption of probiotic
yoghurt or a multispecies
probiotic capsule significantly
improved GHQ-28 and DASS
scores.
Probiotic supplementation in
patients with MDD had
significant reduction in mean
BDI scores.
Conclusions
Q.X. Ng et al.
Journal of Affective Disorders 228 (2018) 13–19
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
double-blind trial
Randomized,
placebocontrolled,
triple-blind trial
controlled,
double-blind trial
Study design
N=40, healthy individuals, Mean age 19.7 years
N=300, healthy older adults, Age ≥ 65 years
N=79, individuals with at least moderate scores on self-report mood
measures, Mean age 35 years
Study sample
Freeze-dried L. casei strain
Shirota (24 × 109 CFU/day)
for 8 weeks
Freeze-dried L. helveticus
R0052 and B. longum R0175
(≥3 × 109 CFU/1.5 g) for 8
weeks
Tablet (once daily)
containing 2 × 109 or 2 ×
1010 L. pentosus strain b240
for 20 weeks
Multispecies probiotic
powder containing B.
bifidum W23, B. lactis W52,
L. acidophilus W37, L. brevis
W63, L. casei W56, L.
salivarius W24, and L. lactis
(W19 and W58) 2.5 × 109
CFU/g for 4 weeks
Probiotic dosage and
duration
NA
NA
QIDSSR16≥11;
DASS≥14
criteria for
CFS
Diagnosis
criteria
LEIDS-r
POMS,
depressiondejection
CGI-S, MADRS,
GAF, DASS
Outcome
measures
Netherlands
Japan
New Zealand
Country of
origin
5
5
5
Jadad
Scale
Probiotic supplementation
reduced self-reported
cognitive reactivity to sad
mood, as quantified by the
LEIDS-r.
Probiotic consumption
produced no significant effect
on any psychological outcome
measure.
Probiotic consumption
improved the elderly's
perception of general health.
BAI scores but no effect on
BDI scores.
Conclusions
Abbreviations: BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory II; BDNF, brain-derived neurotrophic factor; CCL, Coping Checklist; CGI-S, Clinical Global Impression Severity Scale; DASS, depression anxiety and stress scale; DSM,
Diagnostic and Statistical Manual of Mental Disorders; EQ-5D-5L, EuroQol 5 dimensions and 5 levels measure of health and wellbeing; GAF, global assessment of functioning; GDS-SF, Geriatric Depression Scale-Short Form; GHQ-28, General Health
Questionnaire-28; GSRS, gastrointestinal symptoms rating scale; HADS, Hospital Anxiety and Depression Scale; HSCL-90, Hopkins Symptom Checklist; MADRS, Montgomery–Åsberg Depression Rating Scale; LEIDS-r, Leiden Index of Depression
Sensitivity-Revised; MDD, major depressive disorder; NA, not applicable; PSS, perceived stress scale; QIDS-SR16, Quick Inventory of Depressive Symptomatology; STAI, State-Trait Anxiety Inventory; std dev, Standard Deviation.
Steenbergen
et al. (2015)
Shinkai et al.
(2013)
Romijn et al.
(2017)
Author, year
Table 1 (continued)
Q.X. Ng et al.
Journal of Affective Disorders 228 (2018) 13–19
16
Journal of Affective Disorders 228 (2018) 13–19
Q.X. Ng et al.
Table 2
Results of Cochrane Collaboration's tool for assessing risk of bias.
Study (author, year)
Sequence generation
Allocation concealment
Blinding
Incomplete outcome data
Selective outcome reporting
Other bias
Akkasheh et al. (2016)
Benton et al. (2007)
Chung et al. (2014)
Messaoudi et al. (2011)
Nishihara et al. (2014)
Mohammadi et al. (2016)
Östlund-Lagerström et al. (2016)
Pinto-Sanchez et al. (2017)
Rao et al. (2009)
Romijn et al. (2017)
Shinkai et al. (2013)
Steenbergen et al. (2015)
+
?
+
+
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+
+
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+
+
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+
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+
+
?
?
+
+
?
+
?
+
+
+
+
+
+
+
+
+
+
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+
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+
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+
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+
+
+
+
+
+
+
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–
–
?
–
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+
+
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?
?
Key: + low risk of bias; - high risk of bias;? unclear risk of bias.
Fig. 4. Forest plot showing subgroup analysis of studies conducted in individuals with
mild-moderate mood symptoms.
Fig. 2. Funnel plot to assess publication bias Egger test for publication bias=−0.2048,
95% CI −0.975 to 0.566, P=0.5496.
Fig. 5. Forest plot showing subgroup analysis of studies conducted in healthy individuals.
4. 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 studies.
These results differ significantly from the findings of a previous
Fig. 3. Forest plot showing the standardized mean difference in mood symptoms, comparing probiotic supplementation and placebo.
conclusions of one of the abstracted studies (Benton et al., 2007). It is
more reasonable to expect a demonstration of the benefits of an intervention where baseline values are low, as there is greater room for
improvement .
17
Journal of Affective Disorders 228 (2018) 13–19
Q.X. Ng et al.
capsules and powders and non-conventional methods such as cheeses,
yoghurts and milk. These are all associated with reduced bacterial
survival as tablet processing requires bacteria to tolerate temperatures
of up to 60 °C (Roueche et al., 2006), while commercial food products
are less able to protect bacteria against hostile physiological environments (Govender et al., 2014). The latter is especially important as
probiotics must survive gastric transit in order to exert a health-promoting effect in the intestines (Bezkorovainy, 2001). In this metaanalysis, 2 studies used non-conventional methods of delivery, 4 used
tablets/powders, 3 opted for freeze dried formulations, while one did
not specify the means of preparation. Of the 3 trials that made use of
freeze-dried probiotics, two trials found them to have a positive impact
on mood.
Despite vastly improved knowledge on the clinical uses of probiotics, many unanswered questions remain regarding their use in mental
health. Interestingly, a longitudinal study investigating the link between probiotic yoghurt and depression risk, found that consumption of
low-fat yoghurt was associated with a higher incidence of depression
while the opposite was true for full-fat yoghurt (Perez-Cornago et al.,
2016). Since the bacterial concentrations of both yoghurts were comparable, the probiotic hypothesis does not appear to fully explain the
contrasting associations. This study highlights some of the present gaps
in knowledge and stresses the need for further investigation in the field.
Given the current challenges facing the use of probiotics, it is vital
that more research is done to clarify their mechanism of action and
identify their use in depression. With the majority of existing RCTs
being conducted in healthy individuals, it is difficult to extrapolate
current results to individuals with depressive disorders. However, close
analysis of the mood/depressive scale in studies of healthy subjects
(Messaoudi et al., 2011; Steenbergen et al., 2015) revealed a rather
high reported score, meaning that the study population, although not
formally diagnosed with depression, did tend towards depression. Also,
the study conducted by Pinto-Sanchez et al. (2017) was on patients with
irritable bowel syndrome (IBS), which could be a significant confounding factor. It is therefore essential that future studies investigate
the effects of probiotics on a greater number of patients with clinically
diagnosed MDD. Furthermore, as long term treatment is often necessary
in the management of depression (Blier et al., 2007), follow-up studies
over a longer duration should be planned to ensure that any effect
observed is stable.
meta-analysis by Huang et al. (2016) that collated data from 5 randomized clinical trials (RCTs) and found the effects of probiotics on mood
to be statistically significant in both depressed and healthy individuals
(overall SMD −0.30, 95% CI −0.51 to −0.09, p=0.005). The previous
meta-analysis analyzed only 5 RCTs, of which only one was conducted
in depressed patients. This meta-analysis includes five additional RCTs,
and in particular, 2 new studies conducted in individuals with mildmoderate depressive symptoms. This study is therefore a significant and
novel contribution to current literature.
Despite insubstantial evidence for the use of probiotics to alleviate
depressive symptoms, the link between gut microbiota and neuropsychiatric function is a well-researched phenomenon. Modulation of
the bidirectional gut-brain axis is thought to be partly facilitated by gut
microbiota through neurological, endocrine and immune pathways
(Carabotti et al., 2015). The former two routes of communication are
especially important in the context of depression, anxiety and other
mood disorders. Neurologically, the vagus nerve and enteric nervous
system have together been shown to produce both anxiogenic (Lyte
et al., 2006) and anxiolytic (Bercik et al., 2011) effects based on stimuli
from gut bacteria. In doing so, the gut microbiome has a direct impact
on stress-reactivity, with the vagus nerve acting as a crucial route of
communication. Moreover, microbial biosynthesis and modulation of
neurotransmitters such as serotonin (Yano et al., 2015) and GABA
(Barrett et al., 2012) forms another mechanism by which gut microflora
can influence brain function and affect mood. With regard to endocrine
mediation, secretion of cortisol through the HPA axis (in response to
stress) is known to promote intestinal permeability to Gram-negative
bacteria and thus alter the composition of the gut microbiome (Tannock
and Savage, 1974). Bacterial toxins and waste-products are released
into systemic circulation and act to trigger immune responses that
further up-regulate cortisol production via the HPA axis (Kelly et al.,
2015). This “leaky gut” response to stress has been evidenced by various clinical trials that have found the GI flora of depressed patients to
comprise a higher proportion of pathogenic Gram-negative microbes
(Goehler et al., 2008; Jiang et al., 2015). Patients with depression had
significantly increased levels of Enterobacteriaceae and Alistipes but
lowered levels of Faecalibacterium (Jiang et al., 2015).
In light of the intricate interactions between gut microbiota and
brain function, a number of studies have tried to elucidate the role of
probiotics in the field of mental health. Preclinical studies in animal
models have found that probiotic administration downregulates the
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). Despite promising pre-clinical data, a range of
unresolved concerns regarding the administration and pharmacodynamics of probiotic supplements have made it difficult to confirm and
quantify their clinical application and efficacy.
Inter-study discrepancies with respect to probiotic dosing and
treatment durations have impaired the comparability of current clinical
trials and reduced the capacity to draw meaningful conclusions through
meta-analyses. Likewise, the inconsistent use of bacterial strains and
strain combinations is also likely to impact trial results, as certain
bacteria are known to produce superior anti-depressant effects compared to others (Mayer et al., 2014; Savignac et al., 2014). More research is needed to identify the ideal dose, treatment duration and
bacterial species/strains that are most likely to have the greatest impact
on mood.
Another major drawback to probiotic use is their in vitro and in vivo
stability and viability. With a wide range of preparations available for
probiotic delivery, it is important to consider the advantages and
drawbacks of each method. Freeze dried formulations have thus far
been the preferred mode of delivery, as this processing technique preserves bacterial viability to the greatest extent (Bolla et al., 2011).
Other modes of delivery include conventional methods such as tablets,
5. 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 depressed patients. Future
studies should be conducted in greater samples of patients diagnosed
with MDD and perhaps examine the use of probiotics as an adjunctive
treatment.
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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