Prebiotic intake reduces the waking cortisol response and
alters emotional bias in healthy volunteers
Kristin Schmidt1, Philip Cowen1, Catherine J Harmer1, George Tzortzis2, Philip WJ Burnet1
Background
Compelling evidence links the enteric gut
microbiota and brain function, which has led
to renewed efforts to identify strains that confer
a beneficial effect upon the host (probiotics; 1, 2).
Rodent studies implicate the microbiome as
essential to early-life programming of the
hypothalamic-pituitary-adrenal (HPA) axis
and show reductions in anxiety phenotypes
and corticosterone3,4.
Brain-area dependent effects5 exerted via multiple
mechanisms of action such as the immune
system, vagus nerve, and serotonergic pathways
hint at the complexity of the microbiome’s
downstream effects.
In humans, preliminary results support the ability
of gut microbiota to affect cortisol levels6,7 and
neural correlates of emotional processing8. This
has led to increased research on probiotics’ ability to manipulate neural and endocrine targets in
stress-related disorders such as irritable bowel
disease, depression and anxiety.
However, there may be significant scope to
improve manipulations through the use of
prebiotics, non-digestible dietary oligosaccharides
that can support the sustained proliferation of
multiple probiotic strains.
Our study extends findings to effects of two
strains of prebiotics on behavioural processing of
emotional information and the HPA axis.
Methods & Results
Participants
Forty-five healthy volunteers (22 males) received
one of two prebiotics (fructooligosaccharides
[FOS] or Bimuno-galactooligosaccharides [BGOS]) or a placebo at 5.5g per day for 3 weeks.
Cortisol
The salivary cortisol awakening response (CAR)
was sampled before and after prebiotic/placebo
administration to assess HPA axis activity. CAR
was confirmed by increased levels 15, 30, 45, and
60 minutes after waking (F(2.41, 98.63)=58.61,
p<0.001, follow-up comparisons all p<0.001]).
Salivary cortisol did not differ significantly
between groups at baseline but was significantly
lower following B-GOS compared with placebo
(day x group x time ANOVA, day x group
interaction [F(2,41)=3.61, p<0.05], follow-up
effects of group at baseline [F(2,41)=1.08, n.s.]
and
post-prebiotics
[F(2,41)=4.20,p<0.05;
Placebo vs. GOS p<0.05, all others n.s.]).
Attentional dot-probe
Analysis of behavioural data revealed decreased
attentional vigilance to negative versus positive
information in a dot-probe task after B-GOS
compared to placebo (group x emotion x masking
condition [F(2,41)=3.14, p=0.05], follow-up
valence x group interaction in the masked
[F(2,41)=.85, n.s.] and unmasked [F(2,41)=4.29,
p<0.05, Placebo vs. GOS p<0.05, all others n.s.]
conditions).
Cortisol awakening response before and after 21 days of prebiotic supplement ingestion
*p<.05
*
*
*
Attentional dot-probe paradigm
• 60 negative and 60 positive words were paired with neutral
words and presented on a computer screen.
• Unmasked word pairs were presented for 500ms, masked word
pairs for 17ms after which a mask was displayed for 483ms.
• Words / masks were replaced by a probe (either * or **) in the
location of one of the preceding stimuli and participants were
asked to respond (indicating the number of stars by pressing a
key) as quickly and accurately as possible.
• Attentional vigilance scores were calculated for each
participant by subtracting the reaction time from trials when
probes appeared in the same position as the emotional word
(congruent trials) from trials when probes appeared in the
opposite position to the emotional word (incongruent trials).
Attentional vigilance as measured by the dot-probe paradigm after prebiotic administration
Conclusions
Our findings support a role of gut microbiota in affective information processing and the regulation of the HPA axis. These effects were limited to the BGOS prebiotic and were not found after administration of a FOS prebiotic.
The study implicates that:
The manipulation of gut microbiota with B-GOS alters HPA axis responsivity in healthy volunteers. This extends findings of HPA axis
manipulations with probiotics in humans and rodents to the use of prebiotics (nutrients that aid the growth of intrinsic gut microbiota).
B-GOS modifies emotional biases, as it was shown to increase positive versus negative vigilance compared to placebo. Attentional
vigilance is key to threat-related information processing and can be modified by anxiolytics9,10.
While the precise mechanisms of action of prebiotics are still relatively unknown, they are known to include the immune system, which
may explain effects on both the HPA axis (via the adrenal glands) and attentional vigilance (e.g. via the hypothalamus). However, other
relevant pathways linking the gut microbiota and brain include the vagus nerve and serotonergic system 11.
References
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This poster is financially supported by the BBSRC and Clasado Ltd, and an MRC Studentship (KS). We thank Steven Errington for his help with data collection.
Copyright © 2014 Kristin Schmidt kristin.schmidt@psych.ox.ac.uk
1Department of Psychiatry, University of Oxford, Warneford Hospital, Neurosciences Building, Oxford OX3 7JX, UK 2Clasado Research Services Ltd, Reading, RG6 6BZ, UK
P.1.e.003
Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers
K. Schmidt 1, P. Cowen 1, C.J. Harmer 1, G. Tzortzis 2, P.W.J. Burnet 1
1University of Oxforda Department of Psychiatrya Oxforda United Kingdom
2Clasado Research Services Ltda Clasado Ltda Readinga United Kingdom
Background: There is now compelling evidence for a link between gut microbiota and brain function in both
rodents and humans [1]. A recent fMRI study extended these findings to show that ingestion of probiotics
astrains of gut bacteria that confer a beneficial effect on their host) can modulate the neural correlates of
emotional processing [2], and abnormalities in the processing of emotional information are strongly linked to
psychiatric disorders such as anxiety and depression. Further, the hypothalamic–pituitary–adrenal aHPA) axis,
often dysregulated in patients with aand those at risk of) depression and anxiety, impacts affective and memory
processing and has strong bidirectional links with the gut microbiome [3]. The present study explored the effects
of prebiotics – nutrients that proliferate several intrinsic gut microbiota in the host – on HPA axis activity and
emotional processing in healthy volunteers.
Methods: Forty-five healthy volunteers a22 males) received one of two prebiotics afructooligosaccharides [FOS] or
Bimuno-galactooligosaccharides [B-GOS]) or a placebo for 3 weeks. The salivary cortisol awakening response
aCAR) was sampled before and after prebiotic/placebo administration to assess HPA axis activity. On the final
day of treatment participants completed a computerised task battery assessing the processing of emotionally
salient information.
Results: The salivary CAR did not differ significantly between groups at baseline but was significantly lower after
B-GOS compared with placebo aday × group × time ANOVA, day × group interaction [Fa2,41)=3.61, p<0.05]
followed-up with group × time ANOVAs [main effects of group: baseline: Fa2,41)=1.08, n.s., post: Fa2,41)=4.20,
p<0.05; Placebo vs. GOS p<0.05, all others p>0.40]). Analysis of behavioural data revealed decreased
attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to
placebo agroup × emotion × masking condition [Fa2,41)=3.14, p=0.05] follow-up ANOVAs [valence × group
interaction: masked: Fa2,41)=0.85, n.s.; unmasked: Fa2,41)=4.29, p<0.05, Placebo vs. GOS p<0.05, all
others n.s.]).
Conclusions: Our study demonstrates that the manipulation of gut microbiota with B-GOS alters HPA axis
responsivity in healthy volunteers, which is in keeping with the effects of probiotics. In rodents, the gut
microbiome has an important role in regulating the HPA axis early in life, however, as of yet much less is known
from human populations. B-GOS was also shown to increase the processing of positive versus negative
attentional vigilance compared to placebo, which supports findings that the modulation of gut microbiota with
probiotics has subjective anxiolytic effects since attentional vigilance is believed to play a key role in anxiety and
its modulation by anxiolytics. No effects were found after administration of a FOS prebiotic. Overall, novel
evidence supports the notion that manipulations of gut microbiota show widespread effects on central functioning
and behavioural phenotypes via the HPA axis, as well as the vagus nerve, serotonergic system, and immune
system [1]. While the exact mechanisms of action of pre- and probiotics in healthy and clinical populations and
their relation to the processing of emotional information are still relatively poorly defined, our study supports
their role in affective information processing and the regulation of the HPA axis.
1. Cryan, J.F., Dinan, T.G., 2012. Mind-altering microorganisms: the impact of the gut microbiota on brain and
behaviour. Nature Reviews Neuroscience 13, 701–712.
2. Tilisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S.,
Trotin, B., Naliboff, B., Mayer, E.A., 2013. Consumption of fermented milk product with probiotic modulates brain
activity. Gastroenterology 144a7), 1394–1401.
3. Dinan, T.G., Cryan, J.F. 2012. Regulation of the stress response by the gut microbiota: implications for
psychoneuroendocrinology. Psychoneuroendocrinology 37a9), 1369–1378.
Disclosure statement: This poster is financially supported by the BBSRC and Clasado Ltd, and an MRC
Studentship aKS).
Citation: Eur Neuropsychopharmacol. 2014;24aSuppl 2):S191
Keywords
Psychoneuroendocrinology
Anxiety disorders
Stress