OPINION THE BIG IDEA
A light on psychobiotics
The mind-altering effects of gut bacteria are finally being understood. This knowledge
offers a new way to improve our mental health, say John Cryan and Tim othy Dinan
WE HAVE all experienced the influence o f gut
bacteria on our emotions. Just think how you
felt the last tim e you had a stom ach bug. Now
it is becom ing clear that certain gut bacteria can
positively influence our m ood and behaviour.
The w ay they achieve this is gradually being
uncovered, raising the possibility o f unlocking
new ways to treat neurobehavioural disorders
such as depression and obsessive-compulsive
disorder (OCD).
We acquire our intestinal microbes
im m ediately afterbirth, and live in an
im portant sym biotic relationship w ith them.
There are far m ore bacteria in your gut than
cells in your body, and their weight roughly
equals that o f your brain. These bacteria have
a vast array o f genes, capable o f producing
hundreds if not thousands o f chemicals,
m any o f w hich influence your brain. In fact,
bacteria produce some o f the same m olecules
as those used in brain signalling, such
as dopamine, serotonin and gamma-
am inobutyric acid (GABA). Furthermore,
the brain is predom inantly m ade o f fats,
and m any o f these fats are also produced by
the m etabolic activity o f bacteria.
In the absence o f gut bacteria, brain
structure and function are altered. Studies o f
m ice reared in a germ-free environm ent, with
no exposure to bacteria, show that such mice
have alterations in m emory, em otional state
and behaviour. They show autistic patterns of
behaviour, spending as m uch tim e focusing
on inanim ate objects as on other mice. This
behavioural change is driven b y alterations in
the underlying brain chemistry. For example,
dramatic changes in serotonin transm ission
are seen, together w ith changes in key
m olecules such as brain-derived neurotrophic
factor, which plays a fundam ental role in
form ing new synapses.
These findings give weight to the notion
o f probiotics -b acteria w ith a health benefit.
Probiotics were first proposed b y Russian
28 |NewScientist |25 January 2014
biologist Elie M etchnikoff who, in the early vagus nerve, w hich connects the brain and
1900s, observed that people living in a region gut. When this nerve is severed no effect on
o f Bulgaria w ho consum ed ferm ented food anxiety or on GABA receptors is seen following
tended to live longer. However, it now seems psychobiotic treatment w ith I. rhamnosus.
that certain bacteria - dubbed psychobiotics - L. rhamnosus has also been shown to
m ight have a m ental-health benefit, too. alleviate OCD-like behaviours in mice.
Although the field o f psychobiotics is in Interestingly, this bacterium not only alters
its infancy, there are already prom ising signs. GABA receptors in the brain but has been
Last year, for instance, researchers from the shown to synthesise and release GABA. Other
California Institute o f Technology in Pasadena evidence supports the view that gut bacteria
showed that w hen the bacterium Bacteroides m ay influence the brain in routes other than
fragilis'was given early in life, it corrected the vagus nerve - b y altering the im m une
som e o f the behavioural and gastrointestinal system and via the m anufacture o f short-
chain fatty acids, for example.
"You have more gut bacteria Just as certain genes render bacteria
pathogenic, it is likely that clusters o f genes
than bodily cells, and they w ithin gut bacteria provide m ental health
are as heavy as your brain" benefits. However, the essential genes
for effective psychobiotics have yet to be
deficits in a m ouse m odel o f autism. And established. It m ay be that, in the future,
previous reports indicate that Bifidobacterium the ideal psychobiotic will be a genetically
infantis is effective in an animal m odel of m odified organism containing genes from
depression. several different bacteria.
How exactly do gut bacteria influence the In the m eantim e, cocktails o f bacteria are
brain? The m echanism s are becom ing clear. likely to be m ore effective than single strains
The bacterium Lactobacillus rhamnosus, in producing health benefits. For example,
w hich is used in dairy products, has potent a 2011 study showed that a com bination o f
anti-anxiety effects in animals, and works by Lactobacillus helveticus and Bifidobacterium
changing the expression o f GABA receptors in longum reduced anxiety and depressive
the brain. These changes are mediated b y the sym ptom s in healthy volunteers. A 2013
Microbiota with personality
The transplantation of faecal could FMT be useful in treating anxious - and vice versa.
microbes (FMT) from a healthy neuropsychiatric conditions too? If such effects can be
individual into a recipient has Intriguingly, a 2011 study by translated to humans they
emerged as an effective researchers in Canada showed have marked implications for
treatment for life-threatening that anxious mice have different development of microbial-based
Clostridium difficile infection. microbiota compared with therapies for mental disorders.
The success of this approach has normal mice, and that It also means that would-be FMT
focused attention on FMT to transplantation of their donors may need to be screened
treat gastrointestinal, immune microbiota into the normal for mental health issues as well
and metabolic disorders, but mice makes the normal mice as infectious disease.
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What goes on in our gut m ay have profound

effects on w h at goes on in our mind

neuroim aging study showed that a fermented

m ilk product containing four different
probiotic bacteria was associated w ith the
reduced response o f a brain network involved
in the processing o f em otion and sensation.
And certain strains o f bacteria can reduce the
sym ptom s o f irritable bowel syndrome,
a com m on stress-related disorder o f the brain-
gut axis. This is probably achieved through a
reduction in levels o f the “ stress horm one”
PROFILES cortisol and o f inflam m atory m olecules
John Cryan is a professor of produced b y the im m une system.
anatomy and neuroscience These findings are promising, but we
and Tim othy Dinan is a are still a long w ay from the developm ent
professor of psychiatry, o f clinically proven psychobiotics and it
both at University College remains to be seen w hether they are capable
Cork in Ireland. They are o f acting like - or perhaps even replacing -
principal investigators at antidepressants. At a tim e w hen prescriptions
UCC's Alimentary for antidepressants have reached record levels,
Pharmabiotic Centre, effective natural alternatives w ith fewer side
focusing on the interaction effects would be welcome. We are currently
between stress and the com pleting a study o f the gut m icrobiota in
brain-gut axis in relation to people w ith severe depression. If we find
depression, cognition and consistent alterations, this w ill provide a
irritable bowel syndrome strong rationale for targeting depression
w ith a suitable psychobiotic. We are also
about to start a placebo-controlled study o f
Lactobacillus brevis in treating anxiety in
healthy volunteers.
We must, however, sound a note o f caution.
Despite m arketing claims to the contrary,
most putative probiotics have no psychobiotic
activity. Until recently, lax regulation in both
the US and the European Union allowed
m anufacturers to make outlandish claims
w ithout supporting data. This situation is
changing and w ill protect consumers from
fraudulent marketing, but the reality is that
only a small percentage o f bacteria tested
have positive neurobehavioural effects.
Some bacteria fail to survive storage in
the health food store or are eliminated
by acidity in the stomach. Even if they do
survive gut transit, they m ay be devoid
o f health benefits.
In the 20th century, the m ajor focus o f
m icrobiological research was on finding
ways to kill microbes via antibiotics. This
century the focus has changed somewhat,
w ith a recognition o f the health benefits
o f bacteria, not just from an im m unity
perspective but from a m ental health one.
Today, in richer nations, the impact o f stress
on health is perhaps as great as the threat
from harm ful bacteria. Psychobiotics have
enorm ous potential. ■

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