Cognition, Probiotics, Diet and the Gut Microbiota-Brain Axis

Manalo, Karen Paula V.

December 1, 2018

ABSTRACT
The gut microbiota-brain axis has been shown to have a bidirectional relationship. With
this link in mind, several studies have been developed in understanding not just their relationship
but also their applications as in probiotics intake, diet, and cognition of individuals. This special
topic presents the recently discovered neuropod which is likely one of the most direct gut-brain
link; the effect of probiotics in gut-microbiota composition and their subsequent influences on
cognition and behavior; and finally, the triad relationship among diet, gut-microbiota, and the
brain. This report reviews the observations on germ free mice and their cognitive and behavioural
performances. This also talks about the effect of probiotics on behavior and brain activities.
Furthermore, this paper presents some kinds of diet that affect gut microbiota composition which
ultimately affects the brain and its functions.

Introduction metabolites and the promotion of anti-inflammatory

Several studies have already pointed out that the
gut microbiota and the brain have a bidirectional
relationship. The models presented by Wang and Wang
(2016), Dinan et al. (2015), and Bauer, Huus, and Finlay
(2016) all showed this. As previously reported by Diaz
Hiejtz (2011 in Wang & Wang, 2016) germ free (GF)
mice and specific-pathogen-free (SPF) environment
grown mice showed differences in their behaviours. Gut
microbiota with symbiotic relationship with humans have
been shown to influence the brain by synthesizing
metabolites of neurotransmitters and short chain fatty
environment.
Not only do Bifidobacteria and other probiotics
promote health but they also play a role in the gut-brain
axis. This paper aims to dig deeper into the bidirectional
connection of the gut microbiota-brain axis particularly
the discovery of the neuropod, the axis’ relationship on
probiotics, diet, and consequent behavioral effects.
The Neuropod
Steenbergen, Sellaro, van Hemert, Bosch,

acids. Examples are the Bifidobacterium infantis which Colzato (2015) said that the gut and the brain are

synthesizes the precursors of serotonin and tryptophan connected via neural, endocrine, and immune pathways.

(Desbonnet et al., 2008 in Dinan et al., 2015) and the To better see the connection via the endocrine pathway,

Bifidobacterium longum which affects brain derived- Bohórquez and colleagues (2014) were able to identify

neurotrophic factors (Bercik at al. 2011 in Dinan et al., what they call the neuropod located in the enteroendocrine

2015). As Quigley (2017) discussed, Bifidobacteria cells. They described a neuropod to have axon-like

species are known as probiotics which function for properties that has a role in hormonal secretion (Figure 1).

protection against pathogens, improvement of the gut Furthermore, they found out that enteroendocrine cells

barrier, production of water-soluble vitamins, control of containing neuropods are enhanced by neurotrophic

the synthesis of potentially toxic and carcinogenic factors NGF- β and artemin. They also said that the
discovery of the neuropod gives yet another
understanding of the relationship between the gut and the
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brain. This finding is in line with Desbonnet et al. (2008,
2010 in Steenbergen et al., 2015) who said that tryptophan
produced by gut microbiota reaches the brain via the
endocrine pathway.
Figure 1. The emerging model for the intestinal
enteroendocrine cell by Bohórquez and colleagues
(2014)
Despite that more studies are needed to better
understand the link between the gut and the brain, it is for
sure that such connection exists. Because of this, it is also
of great importance to learn more about how the link can
affect our behavior, cognition, and mental health in
general. In addition, it is also of great concern to
understand how several factors that affect gut microbiota
can also have a subsequent effect on our brains. Some of
these are probiotics and diet.
Gut Microbiota-Brain Axis and Cognition
Geurts et al. (2013) and Chen et al. (2013 in
Dinan, Stilling, Stanton, & Cryan, 2015) said that humans
and gut microbes have a symbiotic relationship in terms
of humans providing nutrients for the microbes and the
microbes allowing humans to achieve maximum brain
development and functioning. This is in line with
Montiel-Castro et al. (2013 in Dinan et al., 2015) who also
said that humans would not have the optimal level of
cognition and emotional functioning if it weren’t for the
symbiotic microbiota. Desbonnet et al. (2014 in Dinan et
al., 2015) even stated that gut microbes do have an
important role in the unconscious regulation of human
behavior. Such relationship was seen upon the
observation of the changes in human neurochemistry
when gut microbes were removed (Dinan et al., 2015).
Dinan et al. (2015) also presented a model showing how
human cognition and behavior is influenced by the
absence of some microorganisms (Figure 2).
Figure 2. Major deficits in cognition, behavior and
neurochemistry observed in GF mice from Dinan et al.
(2015)
Figure 2 shows that germ free mice have poor to
undeveloped non-spatial, working memory, and cognitive
functions as a result of decreased BDNF. These findings
are supported by Wall et al. (2012 in Dinan et al., 2015)
who found out that mice which ingested B. breve
NCIMB702258 but not B. breve 6330 had influenced
brain fatty acid composition which further resulted to
higher arachidonic acid (AA) and docosahexaenoic acid
(DHA) concentrations. Furthermore, they found out that
these have possible clinical implications as the fatty acids
have significant roles in memory and learning. In their
study with adults, Claesson et al. (2011, 2012 in Dinan et
al., 2015) found out a causal relationship between very
low gut microbial diversity and poor cognition among the
elderly.
Gut Microbiota-Brain Axis and Probiotics
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 Distrutti et al. (2014) presented the VSL#3 which
is “a probiotic mixture” made up of 8 Gram-positive
bacterial strains. They treated aged rats with VSL#3 and
found a major change in the composition and an increased
abundance in the intestinal microbiota particularly
the Actinobacteria and Bacterioidetes. This was the
opposite from the control-treated aged rats. They further
found out that VSL#3 treatment regulated gene
expression in brain tissue as observed from genes that
influence processes of inflammation and neuroplasticity.
They concluded that the results of their study supports the
hypothesis that intestinal microbiota can be controlled to
have a positive influence on neuronal activity particularly
in age-related long-term potentiation (LTP) deficits.
They also found an increase in the BDNF and synapsin
important for synapses and neural connections.
Figure 3A. LS#3 treatment significantly increased
expression of BDNF mRNA in hippocampal tissue
Figure 3B. A significant VSL#3 treatment effect on
synapsin was observed in aged rats
Steenbergen, Sellaro, van Hemert, Bosch and
Colzato (2015) conducted a research which showed the
first evidence that probiotic intake can reduce negative
thoughts due to low mood in individuals who are not
depressed. They used several species of Bifidobacteria
and Lactobacillus such as Bifidobacterium bifidum W23,
Bifidobacterium lactis W52, Lactobacillus acidophilus
W37, Lactobacillus brevis W63, Lactobacillus casei
W56, Lactobacillus salivarius W24, and Lactococcus
lactis (W19 and W58). In their study, 20 healthy
individuals with no mood disorders were given a 4-week
probiotic food-supplement intervention with the different
probiotic species. There were also 20 control individuals
given inert placebo during the same period. Their
cognitive reactivities were evaluated using the Leiden
index of depression sensitivity scale before and after the
intervention. As what was previously mentioned, the
individuals who had the 4-week probiotic intervention
showed a lowered overall cognitive reaction to sad mood.
They concluded that probiotic supplements opens more
research as possible preventive measure for depression.
Several other previous studies show that strains
of probiotics Lactobacillus and Bifidobacteria have the
ability to improve brain functions in rodents and humans.
In fact, Oriach et al., (2016) even said that these
microorganisms can be possible psychobiotics as part of
treatment in psychiatric disorders.
Gut Microbiota-Brain Axis and Diet
Kashtanova and colleagues (2016) said that diet
is one of the major aspects in knowing the composition of
the gut microbiota. They added that several other factors
such as cooking, addition of nutrients, and intake of
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probiotics affect the gut microbiota composition. Figure 4
shows the determinants of the gut microbiota.
Figure 4. Factors influencing gut microbiota retrieved
from Kashtanova et al. (2016)
As shown above, gut microbiota is affected by
several factors such as mother’s health and diet, breast-
formula-feeding, epigenetics and genetics which
comprises about 60-70% of the influential factors, and
about 30-40% for physical activity and diet (Kashtanova
et al., 2016). This model is in line with Sandhu et al.,
(2016) who said that gut microbiota is affected by several
different factors such as “host genetics, health status,
lifestyle, mode of delivery at birth, antibiotic usage, and
dietary pattern based on different cultural practices.”
This is further supported by Lankelma,
Nieuwdorn, de Vos, and Wiersinga (2015 in Oriach,
Robertson, Stanton, Cryan & Dinan, 2016) who said that
diet was observed to be one of the major determinants
affecting gut microbiota composition through life. In fact,
Zhang et al. (2010 in Oriach et al., 2016) stated that more
than 50% of the diversity of gut microbiota is due to
dietary changes and microbiota composition can be
changed in adults in a few of days (David, 2014 in Oriach
et al., 2016).
Figure 5 also shows the impact of diet on gut
microbiota and the routes of communication in the gut-
brain axis. Oriach et al. (2016) showed that dietary
patterns play a very significant role in either the
maintenance a balanced microbial diversity otherwise
known as symbiosis; or the overgrowth of pathogens
known as dysbiosis. Dysbiosis results to increased
inflammation and leaky gut. Since diet greatly affects gut
microbiota composition, dietary interventions may also
affect the gut brain axis as well as regulate the functions
of the central nervous system (CNS) (Oriach et al., 2016).
Figure 5. Impact of diet on gut microbiota-brain axis in
healthy and unhealthy statuses (Oriach et al., 2016)
Production of microbial metabolites are also
significant in understanding how microbiota influences
the brain and if they are beneficial or not. Despite that
there is scanty study on their mechanisms, Figure 6 shows
bacterial metabolites from carbohydrates, proteins, and
fats obtained from food.
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 ways and shows the link between gut microbiota and
behavior.

In support of this claim, Magnusson et al. (2015)

also conducted a study to determine if Western diets can
affect behavior and gut microbiota. They used two-
month-old mice with three groups such as (1) high-fat diet

Figure 6. Bacterial metabolites from carbohydrates, fet, (2) high-sucrose diet fed, (3) and control. Instead of
proteins, fats (Kashtanova et al., 2016) doing what Jørgensen et al. (2014) performed, they did
fecal microbiome analysis and behavioral tests after two
The clear link between gut microbiota and
weeks of diet change. Their major results identified
behavioral changes have been presented by several
increased composition of Clostridiales, Lactobacillus,
studies claiming that dietary patterns can also contribute
and Lactococcus with decreased Bacteroides in the high-
to behavioral changes.
sucrose diet fed mice. They also found out a poorer
Jørgensen et al. (2014) said that Western diet learning ability as well spatial short term memory
which is high in saturated fat and sugar is responsible for compared to mice in the control group. They concluded
the occurrence of several diseases. Because of this, they that alterations of gut microbiota may influence cognitive
investigated whether saturated fat or high amount of changes particularly related to having a Western diet.
sucrose is responsible for depression-like behavioral
Sandhu et al. (2017) also presented the
symptoms in mice that could also be influenced by the gut
relationship among the diet, gut microbiota, and the brain
microbiota. They had three experimental diets such as (1)
(Figure 7A and B). Figure 7A shows the non-Western
high fat; (2) high sucrose; and (3) control. After thirteen
diet with changed gut microbiota composition following
weeks, they evaluated the gut microbiota composition of
the changes in the short chain fatty acids (SCFA).
the mice and conducted behavioral and cognitive tests.
Observed anxiety and depression are assumed to develop
They found out that mice fed with a high-fat diet had a
from diet-induced changes in the gut microbiota-brain
“significant change” in the gut microbiota composition
axis. Figure 7A also shows the relationship among the
with a lowered composition of Bacteroidetes. Such mice
three factors. It is shown that diet gives the “substrate” for
were also observed to have decreased memory compared
the gut microbiota while the gut microbiota controls diet
to mice given with high-sucrose diet. On the other hand,
via its influence upon the release of satiety hormone.
high-sucrose diet fed mice showed to have less anxiety
Figure 7B shows the integrated peripheral signals coming
than the high-fat diet fed ones. It was noteworthy that a
from the microbiota-derived metabolites from diet that is
significant change in the gut microbiota composition of
sent to the brain for processing.
the mice fed with high-fat diet was correlated with
behavioural changes. No difference where seen in the
other groups. In conclusion, Jørgensen et al. (2014) said
that dietary fat and sucrose influence behavior in different

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 Summary and Conclusion

Studies on the relationship between the gut

microbiota-brain axis has been giving more opportunities
to strengthen and develop research on such area. Aside
from the fact that the gut and the brain have a bidirectional
relationship, it is of significance that the factors affecting
gut microbiota such as probiotics, diet, and even lifestyle
also be taken a look at as well as the subsequent effects
on the brain functions.

Aside from the several models presented in the

initial report, it is noteworthy to learn about the neuropod
cell with axon-like properties in the enteroendocrine cells
which shows a direct link between the gut and the brain.

Several studies have shown that various species

and strains of bacteria such as
Actinobacteria and Bacterioidete and other probiotics can
affect cognition as in learning and memory.

Diet is one of the major factors that contribute to

microbial gut diversity. Many studies have also shown
that there are significant behavioural changes on
individuals and lab mice given high-fat and/or high-
protein food which also affects the gut microbiota
composition.

The studies presented in this report will provide

more opportunities to delve deeper into the actual roles
and interrelationships among diet, probiotics, the gut
microbiota-brain axis, and cognition.

The presented studies provide opportunities for

Figures 7A and 7B. Triad relationship of the diet, gut
further research especially in understanding the potentials
microbiota, and the brain (Sandhu et al., 2016)
of microorganisms in treating and improving mental
functioning of individuals.

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