809379

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PPSXXX10.1177/1745691618809379Smith, WisselMicrobes and the Mind

ASSOCIATION FOR
PSYCHOLOGICAL SCIENCE

Perspectives on Psychological Science

Microbes and the Mind: How Bacteria 2019, Vol. 14(3) 397­–418
© The Author(s) 2019
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DOI: 10.1177/1745691618809379
https://doi.org/10.1177/1745691618809379

Cognition, Social Relationships, www.psychologicalscience.org/PPS

Development, and Pathology

Leigh K. Smith1 and Emily F. Wissel2

1
Department of Psychology, University of California, Davis, and 2School of Nursing, Emory University

Abstract
Recent data suggest that the human body is not so exclusively human after all. Specifically, humans share their bodies
with approximately 10 trillion microorganisms, collectively known as the microbiome. Chief among these microbes
are bacteria, and there is a growing consensus that they are critical to virtually all facets of normative functioning.
This article reviews the ways in which bacteria shape affect, neurological processes, cognition, social relationships,
development, and psychological pathology. To date, the vast majority of research on interactions between microbes
and humans has been conducted by scientists outside the field of psychology, despite the fact that psychological
scientists are experts in many of the topics being explored. This review aims to orient psychological scientists to the
most relevant research and perspectives regarding the microbiome so that we might contribute to the now widespread,
interdisciplinary effort to understand the relationship between microbes and the mind.

Keywords
microbiome, bacteria, emotion, gut–brain axis, cognition, social relationships, development, mental health

It is widely accepted that mental states are influenced
by bodily processes (Blascovich & Mendes, 2010), but
it is time to expand the concept of “body” to include
the 10 trillion microorganisms that live on and inside
of humans (P. Kramer & Bressan, 2015; Sender, Fuchs,
& Milo, 2016). Collectively known as the microbiome,
these organisms include fungi, archaea, and viruses,
but chief among them are bacteria—which, as recent
investigations have uncovered, seem to influence virtu-
ally all facets of the human experience (Anderson,
Cryan, & Dinan, 2017). This review outlines the ways
in which bacteria shape affect, cognition, neurological
processing, social relationships, development, and psy-
chological pathologies. In an interdisciplinary effort,
biological and clinical scientists have carefully seeded
this new research terrain, and psychological scientists
have an important role to play in cultivating the soil—
both theoretically and empirically.
To efficiently orient psychological scientists to the
most relevant research and perspectives regarding the
microbiome, this review is organized by psychological
subfield (e.g., affective science, neuroscience, cognitive
science). Each section presents a rigorous but concise
overview of how bacteria shape variables typically
investigated in each subfield. Collectively, therefore,
this review aims to be accessible to a diverse audience
of researchers. Of key importance is that this review
highlights a large collection of nonclinical findings,
stepping beyond the notion that contact with bacteria
is harmful (R. T. Liu, 2017) and into the fascinating body
of work that demonstrates how bacteria critically sup-
port normative, everyday functioning. Specifically, we
review how an array of psychological experiences are
influenced by both commensal bacteria (those that tend
to be beneficial or harmless, e.g., Lactobacillus species)
and pathogenic bacteria (those that cause disease or
Corresponding Authors:
Leigh K. Smith, University of California, Davis, Department of
Psychology, 135 Young Hall, 1 Shields Ave., Davis, CA 95616
E-mail: leismith@ucdavis.edu
Emily F. Wissel, Emory University, School of Nursing, Wesley Woods
Hospital Office A2076, 1821 Clifton Rd. NE, Atlanta, GA 30329
E-mail: ewissel@emory.edu
398 Smith, Wissel
dysfunction, e.g., Clostridium difficile). An important
note, however, is that whether bacteria play a beneficial
or harmful role is not exclusively determined by their
type. Factors such as their proportion relative to other
microbes, the physiology of the host, and the external
environment all contribute to the type of effects they
will exert. Last, because of recent advances in both
animal and human experimental research, a substantial
amount of the work covered in this review moves past
correlational associations to include direct, causal influ-
ences of the microbiome on psychological and neuro-
logical processes.
Emotion and Affective Science
Bacteria play an important role in shaping affective
states. Affect forms the basis for processing a wide range
of sensory and physiological information (L. F. Barrett
& Bliss-Moreau, 2009; Siegel, Wormwood, Quigley, &
Barrett, 2018), as well as developing a sense of self
(Damasio, 2003), establishing meaningful social bonds
(Algoe, 2012), and promoting approach versus avoid-
ance behaviors (Phaf, Mohr, Rotteveel, & Wicherts,
2014). The brain regions that support affective states
also support essential physiological functioning (e.g.,
allostasis; Kleckner et al., 2017), suggesting that affect
is deeply embodied and fundamentally intertwined with
humans’ physical preservation and survival. The micro-
biome’s ability to shape affect and emotion therefore
indicates that the influence of bacteria may spill over
into every aspect of what it means to be a conscious,
living organism.
Chronic and acute affective states
At the most general level, maintaining a robust popula-
tion of beneficial bacteria in the gut can improve mood
and well-being, whereas the depletion of these bacteria
can negatively affect well-being (Cryan & Dinan, 2012;
Cryan & O’Mahony, 2011; Forsythe, Sudo, Dinan, Taylor,
& Bienenstock, 2010). For example, in a double-blind
placebo-controlled study, medical students consumed
a daily drink composed of probiotics, which are supple-
ments containing live, beneficial bacteria, for 3 months
leading up to their qualifying exams. The students
showed improvements in psychological symptoms
related to chronic stress, as indexed by attenuated
increases in cortisol, improved sleep quality, and
improved parasympathetic activity (Nishida et  al.,
2017). Recent studies have further demonstrated that
male rats that consumed a diet rich in prebiotics, which
is fiber that beneficial microbes can digest, exhibited
decreases in anxiety-like behaviors and altered gene
expression in neural circuits that may support emotion
regulation (Mika et al., 2018). By contrast, chemically
induced colitis—inflammation of the colon—led to
decreases in beneficial intestinal bacteria in rodents and
increases in their behaviors associated with negative
affect, such as anxiety (Bercik, Park, et al., 2011; Davis
et al., 2016) and depression (Slyepchenko et al., 2016).
Bacteria are also related to chronic, trait-like affective
states. For example, Martin et al. (2009) reported that
human subjects who had chronically low or high levels
of anxiety had distinct metabolic profiles indicative of
different gut microbial activity. Furthermore, extended
dietary interventions that directly influenced gut motil-
ity partially normalized these trait-like anxiety-related
differences. Recent studies have also shown that individu-
als who experience chronic negative affect (as indexed
via personality traits such as high neuroticism) have gut
microbiota that are distinct from individuals whose per-
sonalities are characterized by less negative affect and
lower levels of neuroticism (H. Kim et al., 2018).
In a similar demonstration from animal research,
colonizing phenotypically anxious mice (BALB/c mice)
with the microbiota of phenotypically gregarious mice
(Swiss mice) resulted in the typically anxious mice
becoming more gregarious. The reverse was also true—
colonizing gregarious mice with the microbiota of anx-
ious mice induced heightened anxiety-like behaviors
(Bercik, Park, et  al., 2011). Although conducted with
animals, this study and others like it (e.g., Collins, Kassam,
& Bercik, 2013) demonstrate that trait-like affective states
can be “transferred” from one individual to another via
manipulation of the microbiome.
In one of the first studies to examine how bacteria
are related to acute affective experiences, Lencner et al.
(1984) reported that astronauts experiencing momen-
tary emotional distress during shuttle launches showed
distinct alterations in the beneficial bacteria present in
their saliva and feces. Experiments with rodents have
repeatedly demonstrated similar findings. Acute nega-
tive affect brought on by momentary stress (e.g., fear
conditioning, forced swim tests, stress-induced hyper-
thermia) is associated with or directly caused by the
overgrowth of pathogenic bacteria or the depletion of
beneficial bacteria (Bravo et al., 2011; McLean, Bergonzelli,
Collins, & Bercik, 2012; Neufeld, Kang, Bienenstock, &
Foster, 2011).
Mood beyond health
Although it may be tempting to simply conclude that
the microbiome influences health and that health in
turn influences affective states (e.g., “good” bacteria
make you healthy, and healthy people are happy), there
are also several compelling examples of bacteria influ-
encing emotion in which improvements in physical
health were not the primary mediating force. For exam-
ple, a probiotic yogurt drink developed to reduce
Microbes and the Mind 399
constipation was administered to human subjects daily
for 3 weeks. Although the probiotic drink did not influ-
ence the frequency of defecation (the targeted health
outcome), it did influence discrete emotional outcomes.
Consumption of the probiotic drink (compared with a
placebo drink) improved the self-reported mood of
those whose mood was initially poor (Benton, Williams,
& Brown, 2007). In another study, healthy human sub-
jects with no symptoms of physical illness who ingested
a probiotic supplement for 30 days reported significant
decreases in symptoms of psychological distress over
time. Specifically, they exhibited decreases in anxiety
(as assessed by the Hospital Anxiety and Depression
Scale; Zigmond & Snaith, 1983) and fewer symptoms of
depression, anger, and hostility (as assessed by the
respective subscales of the Hopkins Symptom Checklist;
Derogatis, Lipman, Rickels, Uhlenhuth, & Covi, 1974)
compared with those taking a placebo (Messaoudi et al.,
2011).
Strikingly, the positive effects of bacteria on mood
are not limited to how people perceive their own emo-
tions but also how people perceive emotions on the
faces of others. To this end, researchers found that
when healthy women with no gastrointestinal (GI) or
psychiatric symptoms consumed a nonfermented pro-
biotic drink daily for 4 weeks, they showed decreased
reactivity to negative facial expressions on other peo-
ple’s faces (angry and sad faces) compared with sub-
jects who consumed a placebo (Tillisch et  al., 2012).
Taken together, these results suggest that bacteria do
not influence emotions simply by ameliorating poor
health, as all of these human subjects were already
healthy. Examples from animal research also support
this claim. Healthy mice administered beneficial bacte-
ria (compared with healthy mice given a placebo) tend
to be more exploratory and outgoing in their behavior
and show fewer symptoms of helplessness and depres-
sion (Bravo et al., 2011; Davis et al., 2016).
How do bacteria influence emotions, then, if improved
mood is not just an outcome of improved health from
the presence of beneficial bacteria and negative mood
is not just an outcome of poor health induced by patho-
genic bacteria? Although health almost certainly medi-
ates the influence of bacteria on emotion in many cases,
experimental studies also point to evidence that bacteria
can more directly modify a host’s neural functions,
affecting a variety of psychological processes and men-
tal states.
Neuroscience and the Gut–Brain Axis
Evidence from the past decade suggests that the micro-
biome may have just as strong an influence over the
brain as the brain has over the microbiome (Stilling,
Dinan, & Cryan, 2016). Specifically, there is a consensus
emerging that the microbiome and brain communicate
regularly and bidirectionally along a network termed
the gut–brain axis (Allen, Dinan, Clarke, & Cryan, 2017;
Cryan & Dinan, 2012; Wiley et al., 2017). The gut–brain
axis facilitates molecular signaling between microbes
in the GI tract and the central nervous system (CNS)
and peripheral nervous system (PNS). It also facilitates
communication to and from the enteric nervous system
(ENS), which is embedded in the lining of the GI tract
and can function independently of the CNS to regulate
gut motility and composition (Carabotti, Scirocco,
Maselli, & Severi, 2015; Cryan & Dinan, 2012). One of
the most important and well-researched features of gut-
brain communication is the ability of bacteria to both
produce and directly respond to a variety of neuro-
chemicals. These neurochemical signals can travel to
the brain via several biochemical and structural path-
ways along the gut–brain axis. These pathways are
illustrated in Figure 1 and more extensively reviewed
in the “Pathways of Communication” section. The cur-
rent section introduces several key bacterially produced
neurochemicals that have been shown to affect psycho-
logical outcomes relevant to research in our field.
Serotonin
It is well established that serotonin is fundamental to
physical and psychological health, but less is known
about how vitally important it is for GI health ( J. J. Chen
et al., 2001). In fact, approximately 90% of the body’s
serotonin is located along the intestinal tract, where its
primary function is regulating gut motility (Berger,
Gray, & Roth 2009). The serotonin produced in the gut
is also central to healthy nervous system development,
and research with rodents indicates that the activation
of serotonin receptors in the ENS is linked to its
neurogenesis and neuroprotection (De Vadder et  al.,
2018). Given that many people diagnosed with serotonin-
deficit-based mood disorders (e.g., depression, anxiety)
have a comorbid gut disorder (Martin-Subero, Anderson,
Kanchanatawan, Berk, & Maes, 2016), serotonin-based
interventions may be effective in treating both psycho-
logical and gut-related symptoms. In fact, depression
and anxiety symptoms in humans tend to increase in
parallel with GI symptom severity and frequency (Pinto-
Sanchez et  al., 2015), making this comorbidity even
more relevant. Current treatment methods, however,
involve administering a selective serotonin-reuptake
inhibitor that, although effective in ameliorating behav-
ioral symptoms, can have negative effects from long-
term use and does not address the root cause of the
issue (Cohen & Baldessarini, 1985). Alternatively, admin-
istering beneficial bacteria that are known to increase
400 Smith, Wissel

Neurometabolite Production

Endocrine Response

Immune Activation

Vagal Communication
Inner
Intestines

GABA

SCFA Serotonin
IL-10
IgA
LPS IL-6

al Wall
Intestin

Fig. 1.  Pathways of communication along the gut–brain axis. Bacteria can secrete neu-
rotransmitters (e.g., γ-aminobutyric acid, or GABA) that induce intestinal cells to release
molecules that modulate neural signaling within the neurometabolite production pathway—
the enteric nervous system (ENS), central nervous system (CNS), and peripheral nervous
system (PNS). Bacteria can also secrete short-chain fatty acids (SCFAs) that induce neuro-
endocrine cells to convert amino acids into serotonin, which is communicated to the brain
by ENS activity (neuroendocrine response pathway). The overgrowth of pathogenic bacteria
can increase intestinal permeability, releasing harmful bacteria into the bloodstream. This
triggers an immune response and leads to the production of inflammatory immune mol-
ecules—such as interleukin- 6 (IL-6) or IL-10—and antibodies (e.g., immunoglobulin A,
or IgA) that signal to the CNS and PNS (immune activation pathway). Last, information is
routinely passed between the gut and brain along the vagus nerve. Signals from the CNS
can influence motor, sensory, and secretory functions of the intestines, and the intestinal
microbiome can send information about gut motility and composition via afferent vagal
pathways to the CNS (vagal communication pathway).

serotonin levels (Neufeld et  al., 2011; Reigstad et  al., 2003; Nemeroff, 2003). Benzodiazepines are primarily
2015) in the form of a probiotic or by following a diet used to treat anxiety disorders because they bind to
that supports bacteria critical for serotonin production GABA receptors in the brain, making GABA more effi-
may effectively influence mood as well as concomitant cacious. Antidepressants can also be used to treat GABA
GI symptoms. Current research with humans has already imbalances in people who have been diagnosed with
shown that an oral probiotic can improve the affective depression. It is known that certain gut bacteria natu-
symptoms of those suffering from a poor mood (Benton rally produce GABA (E. Barrett, Ross, O’Toole,
et al., 2007), and this may be due in part to the influence Fitzgerald, & Stanton, 2012). Furthermore, when probi-
bacterial populations exert on key neurochemicals. otics are ingested by rodents, they have been found to
alter GABA in the same regionally dependent manner
as benzodiazepines and antidepressants (Bravo et al.,
GABA 2011; Janik et al., 2016). After probiotic treatment with
γ-Aminobutyric acid (GABA) has a strong connection these GABA-producing bacteria, healthy mice demon-
to depression and anxiety disorders; low levels of strate an increase in exploratory behavior (Collins,
GABA correspond to increased depression- and anxiety- Surette, & Bercik, 2012), showing that even a healthy
related symptoms (Cryan & Kaupmann, 2005; Lydiard, population can benefit from probiotics. Likewise, the
Microbes and the Mind 401
administration of commensal bacteria that have been
shown to modulate GABA receptor mRNA expression
in rodents can reduce anxiety, increase the experience
of pleasure, and modulate other affectively laden moti-
vational states (Bravo et al., 2011).
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF) has been
implicated in an array of psychological disorders—such
as major depressive disorder (Kielstein et al., 2015) and
schizophrenia (Nieto, Kukuljan, & Silva, 2013). It has
been consistently found that low levels of BDNF in
humans are associated with poorer psychological out-
comes and that certain medications, such as antidepres-
sants, seem to restore BDNF levels for those who have
an abnormally low supply (B. Chen, Dowlatshahi,
MacQueen, Wang, & Young, 2001; Shimizu et al., 2003).
Recent research has found that having an overabun-
dance of pathogenic bacteria results in significantly less
hippocampal BDNF in mice, which covaries with more
anxious and depressed behaviors. Similar to the effect
of antidepressants, these behavioral markers of anxiety
and depression were attenuated when a probiotic con-
taining Bifidobacterium longum was administered to
the mice (Bercik, Denou, et  al., 2011). Other studies
have also found that having a healthier microbial profile,
either by receiving a probiotic, reducing the abundance
of pathogenic bacteria, or supporting communities of
beneficial bacteria that are already present, results in
more BDNF and exploratory behavior in mice (Collins
et  al., 2012). These findings suggest that optimizing
one’s microbial profile could effectively increase low
BDNF levels.
Deficits in bacteria
Studies in germ-free animals—which live in sterile envi-
ronments and have no exposure to bacteria—have
shown that a lack of bacteria results in many detrimen-
tal neurological consequences (Al-Asmakh & Zadjali,
2015; Cebra, 1999; Collins et  al., 2012). Specifically,
germ-free animals lack key neurometabolites (Wikoff
et  al., 2009), and their brains lack structural integrity
(Luczynski et al., 2016). For instance, the blood–brain
barrier of germ-free mice is not as tight or well pro-
tected as it is in conventional mice (Braniste et  al.,
2014). Furthermore, the microbiome supports the
growth and functioning of microglia cells, which are
essential for mounting immune responses to protect the
brain from pathogens or internal damage. Even the
temporary depletion of a host’s microbiota leads to
structurally and functionally defective microglia in
rodents (Erny et al., 2015). Altogether, bacteria prove
to be not only beneficial but also vital to brain function
and development.
Cognitive Science and Information
Processing
In addition to affecting the brain at both the molecular
and structural level, bacteria influence the emergent
properties of neurological activity. Specifically, the
microbiome has been implicated in a range of cognitive
processes related to an individual’s ability to process,
integrate, and make sense of both novel and familiar
information.
Memory
Encoding and storing information is essential to every-
day functioning both for humans and animals, and bac-
teria play a role in these cognitive processes (Benton,
Williams, & Brown, 2007; Magnusson et  al., 2015;
Messaoudi et al., 2011). For example, in a series of stud-
ies, Gareau et al. (2011) found that having a bacterial
infection that leads to the proliferation of pathogenic
bacteria resulted in memory dysfunction in mice that
had been exposed to a prolonged water-avoidance
stressor, which is a well-established model of psycho-
logical stress in rodents (Saunders et al., 2002). In addi-
tion, germ-free mice exhibited similar stress-induced
memory dysfunction. This memory dysfunction was
prevented when mice received a probiotic containing
an array of commensal bacteria, suggesting that probi-
otics designed to normalize gut bacteria can be benefi-
cial for cognitive processing. Likewise, mice with
enriched diets display increased working and reference
memory (Collins et  al., 2013; Li, Dowd, Scurlock,
Acosta-Martinez, & Lyte, 2009). Recent research with
rodents has demonstrated that probiotics can have
strong and significant effects on both long-term object
recognition and short-term memory for objects in place
(O’Hagan et al., 2017).
These findings may, however, have important mod-
erators. For example, in a recent experimental study
with rodents, the administration of probiotics improved
some types of memory (spatial) but impaired others
(object recognition; Beilharz, Kaakoush, Maniam, &
Morris, 2018). Likewise, antibiotics administered to mice
to cause dysbiosis—which is an unhealthy imbalance
of their internal microbial populations—led to impair-
ments in object recognition but not spatial memory
(Frohlich et al., 2016). These findings suggest that the
type of memory task being assessed and the cognitive
processes it recruits may be differentially affected by
bacteria populations. In addition, the health of subjects’
microbiomes before probiotic intervention as well as
402 Smith, Wissel
their routine diets may also be key variables to account
for. For example, Beilharz, Kaakoush, Maniam, and
Morris (2018) found that administering probiotics to
rats with severely dysregulated microbiomes as a result
of a high-fat diet did indeed improve some types of
memory performance. By comparison, the probiotic
intervention led to memory deficits in healthy rats with
typical microbiomes. In humans, many diets support a
healthy microbiome and, in general, eating more pre-
biotic fiber and fewer processed foods will confer a
health benefit. However, further research will need to
examine when and which bacterial strains most directly
influence memory-related processes and how this inter-
acts with the host diet.
Learning and attention
Research suggests that the microbiome also influences
the ability to process, apply, and ultimately learn from
information. For example, when mice were fed com-
mensal bacteria daily for 11 weeks, they showed sig-
nificant improvements on cognitive tasks. Note that the
improvement depended on the exact type of bacteria
mice ingested. Those fed B. longum showed the most
improvement in object recognition and object discrimi-
nation, followed by those fed Bifidobacterium breve,
whereas control animals who did not receive a bacteria
supplement demonstrated the least improvement and
the poorest performance overall (Savignac, Tramullas,
Kiely, Dinan, & Cryan, 2015). A study that examined the
effects of diet on the microbiome showed similar results.
When tested 2 weeks after a controlled diet change, mice
fed a high-fat or high-sucrose diet that resulted in the
proliferation of pathogenic bacteria exhibited impaired
cognitive flexibility compared with control mice that
were fed a normal diet (Magnusson et al., 2015).
In a recent study with human subjects, participants
who received a 4-week probiotic food supplement
experienced significant reductions in cognitive reactivity
to sad moods compared with a control group that received
a placebo. This effect was driven primarily by decreases
in the rumination and aggressive thoughts linked to sad
moods and therefore provides some of the first evidence
that beneficial bacterial species can influence emotional
states via cognitive pathways (O’Mahony et al., 2014).
Likewise, human subjects who ingested a prebiotic
every day for 3 weeks exhibited less attentional vigi-
lance to negative versus positive stimuli and a subse-
quent decrease in cortisol levels (Schmidt et al., 2015).
In another study that explored the ways in which
cognition and affect may interact to influence learning,
mice were fed the ambient bacteria Mycobacterium
vaccae before completing increasingly complex maze
tasks. The bacteria-fed animals completed the mazes
more quickly than the control animals at all levels of
complexity. This performance was in part attributed to
corresponding decreases in anxiety-related behaviors.
Furthermore, the bacteria-fed mice continued to out-
perform the control mice for a week after the bacteria
had been withdrawn from their diets. However, this
effect did not persist beyond that time frame, suggesting
that the continual rather than intermittent presence of
healthy bacteria is necessary to induce positive cogni-
tive and affective outcomes (Matthews & Jenks, 2013).
These findings also must be interpreted with caution,
as there exists at least one study with humans wherein
the candidate probiotic Lactobacillus rhamnosus failed
to modulate cognitive performance in a randomized
placebo-controlled trial (Kelly et al., 2017). As discussed
above, this highlights the need for further research
aimed at successfully identifying what moderators, as
well as which strains of bacteria, are most likely to
affect cognitive processing in healthy human subjects.
Social Networks and Close Relationships
The relationship that humans have with their commen-
sal bacteria is typically mutually beneficial, and the
reach of people’s microbiomes can extend into their
social networks and influence their interpersonal
behaviors.
Social niches and interpersonal
interactions
The social niche people live in affects their microbiome
from birth to death. Being delivered via vaginal birth
versus cesarean section sets the stage for the forthcoming
bacterial profile of the infant (Dominguez-Bello et  al.,
2010), and the nutrients present in a mother’s breast milk
feed the growing bacterial population in a developing
child (Hinde & German, 2012). This means that within the
first few days after birth, social networks and social prac-
tices are already exerting an influence on the bacteria that
humans will share their bodies with for the rest of their
lives. In fact, all humans emit a relatively unique “micro-
bial cloud” (Meadow et  al., 2015)—a collection of per-
sonal bacteria—that is shed into the surrounding air. This
cloud influences the microbial composition of humans’
external environment, including shared social spaces and
the people in them. Even ethnic affiliation is correlated with
microbiota composition (Mason, Nagaraja, Camerlengo,
Joshi, & Kumar, 2013; Ravel et al., 2011), presumably
because of shared genes, shared diets, shared living spaces,
and other shared cultural experiences.
Bacteria respond not only to whom people are sur­-
round­e d by but also to the content of their social
interactions—especially social stress (Parashar &
Microbes and the Mind 403
Udayabanu, 2016). For instance, mice exposed to socially
aggressive cage mates exhibited substantially altered
gut microbial communities (Bailey et  al., 2011), and
mice exposed to repeated experiences of social defeat
showed disruptions in their balance of intestinal bac-
teria (Galley et al., 2014). Furthermore, the depletion
of beneficial bacteria in mice has been shown to sup-
press normative immune responses after social stress-
ors, such as being repeatedly physically attacked by
other mice (Galley et al., 2014). This suggests that bac-
teria not only respond to stress but may also aid indi-
viduals in the ability to recover after major social
disruptions. Maternal separation, for example, is an
early-life relational stressor that can result in lifelong
disturbances in stress reactivity (e.g., chronic or pro-
longed activation of the hypothalamic-pituitary-adrenal,
or HPA, axis). After maternal separation, baby mice
suffer a significant decrease in beneficial bacteria such
as Lactobacillus species (Bailey & Coe, 1999), whereas
being treated with that same (and other similar) bacteria
before the separation attenuates the stress response, as
indexed by reduced corticosterone levels (Desbonnet
et al., 2010).
A microbiome abundant in beneficial bacteria spe-
cies may even promote prosocial behaviors. Social
interactions are most likely to occur when exploratory
behaviors are enhanced and anxious behaviors are
decreased. There are at least a dozen known strains of
bacteria that exert anxiolytic—or anxiety-reducing—
effects on their hosts and promote exploration of the
environment (Wissel, 2018). Consistent with these find-
ings, germ-free mice exhibit significant social impair-
ments, lacking the normative preference for spending
time with other mice compared with spending time
alone in an empty chamber. Mice with healthy micro-
biomes, on the other hand, are more likely to explore,
interact with novel mice, and demonstrate the norma-
tive motivation to socialize with others (Desbonnet,
Clarke, Shanahan, Dinan, & Cryan, 2014).
Mate selection and intimate relationships
Once people have established a social niche, instances
of interpersonal bacterial exchange become frequent
and periodic. Human romantic relationships may have
an especially strong influence on the composition of
the microbiome, as they offer virtually unparalleled
opportunities for bacterial exchange and colonization
through multiple channels (e.g., mucus membranes,
prolonged skin-to-skin contact).
There is already evidence that people use informa-
tion from other people’s bodies to assess their repro-
ductive fitness. To this end, sexual arousal engenders
a higher tolerance, and even a desire, for biochemical
fluids produced by an interaction partner (Borg & de
Jong, 2012). Kissing, for example, may contribute to
mate selection by offering the opportunity to sample
chemical cues from the saliva that indicate health and
compatibility (Nicholson, 1984), and smelling or tasting
a partner’s sweat may provide similarly rich mating-
relevant information (Bhutta, 2007; Gildersleeve,
Haselton, Larson, & Pillsworth, 2012; Singh & Bronstad,
2001). Not surprisingly, bacteria are an essential ingredi-
ent in each of these mate-selection signals. For exam-
ple, approximately 80 million bacteria are exchanged
in a single mouth-to-mouth kiss, and the more fre-
quently partners kiss, the more similar their oral and
tongue microbiota become (Kort et al., 2014). Likewise,
sweat itself does not have an odor. Rather, the bacteria
colonizing the skin generate the odors that serve as
olfactory cues for health, similarity, and social recogni-
tion (Archie & Theis, 2011; Kligman & Strauss, 1956;
Montiel-Castro, Augusto, Báez-Yáñez Mario, & Pacheco-
López, 2014). Additional markers of reproductive fitness
that bacteria directly shape include clear skin, lustrous
hair, and body mass index (Levkovich et  al., 2013;
Poutahidis et al., 2013; Poutahidis et al., 2014). This work
demonstrates that the microbiome plays an important
role in promoting traits that are used in the mate-selection
process.
Experimental research has demonstrated that bacte-
ria can also shape mate preferences at the actor level.
For example, in an experimental study, administering
antibiotics to fruit flies eliminated their normative pref-
erence for mates that inhabited environments similar
to their own and maintained similar diets (Sharon et al.,
2010). In a departure from their normative behavior,
the fruit flies given the antibiotics selected mates more
indiscriminately, with no preference given to similarity
factors. This suggests that the disruption of the micro-
biome can alter individuals’ mating preferences and
behaviors. Likewise, sexual practices can influence the
microbiome. For example, non-monogamous female
lizards show a more diverse microbiome in their cloaca
than do monogamous females (White, Murielle, Massot,
& Meylan, 2011). In humans, men who maintain monog-
amous relationships can be differentiated from those
who have had extramarital affairs by the bacterial pro-
file of their reproductive organs (or their community
state type; C. M. Liu et al., 2015).
Bacteria also shape mating and relationship pro-
cesses at the hormonal level. Feeding mice certain types
of bacteria elicits the production of oxytocin, a hor-
mone that has been associated with monogamy and
pair bonding, in the brain and bloodstream (Varian
et al., 2016, 2017). Mice treated with the purified bac-
teria Lactobacillus reuteri exhibit increases in testoster-
one, larger testicles, and higher sperm counts and tend
404 Smith, Wissel
to build extra muscle and maintain a competitive edge
in their reproductive efforts (Poutahidis et al., 2014).
At the genetic level, microbes can promote bacteria-
induced alterations in nuclear genes that code for the
production of sex pheromones in animals or that gener-
ate molecules that act as sex attractants (Brucker &
Bordenstein, 2012). It should be noted that the type of
bacteria that are known to possess some of the most
robust psychoactive properties are overrepresented in
the human reproductive organs (e.g., species of Lacto-
bacillus; Perez-Burgos et al., 2013). This suggests that
bacterial transfer via intimate or sexual contact may be
especially likely to influence downstream neurological
and psychological processes. Thus, in an effort to sup-
port their own reproductive success, bacteria have also
shaped the traits and behaviors that drive the reproduc-
tive success of their hosts.
Developmental Psychology and
Bacteria Across the Life Span
The human microbiota undergoes a process of develop-
ment that is coordinated with the development of the
CNS, PNS, ENS, endocrine system, and immune system.
This symbiotic relationship is established early in life
but changes dynamically to meet specific developmen-
tal needs—sometimes prioritizing the needs of the hosts
and other times the needs of the bacteria. For example,
individuals often exhibit different microbial profiles
across different stages of the life span (Hopkins, Sharp,
& Macfarlane, 2002). Specifically, higher proportions of
bacteria dedicated to enriching growth and develop-
ment are often found in infants and children (birth to
11 years old), and larger proportions of bacteria associ-
ated with inflammation and obesity are found in adults
over 70 years old (Hollister et  al., 2015). Thus, the
development of the microbiome can be examined from
a functional perspective. This allows us to identify not
only how humans’ resident bacteria change over time
but also how they shape physical and psychological
development across the life span.
Gestation, birth, and early infancy
The gut and vaginal microbiomes undergo considerable
changes during pregnancy, resulting in a strong mater-
nal signature on the microbial profile of newborns
(Palmer, Bik, DiGiulio, Relman, & Brown, 2007). The
human uterus was previously thought to be sterile, but
recent research suggests that bacteria may actually be
transferred to the fetus via the bloodstream and pla-
centa while still in utero ( Jiménez et al., 2008; Rautava,
Collado, Salminen, & Isolauri, 2012; Satokari et  al.,
2009). Although this work is still in its early stages,
researchers have now catalogued the presence of
numerous bacteria isolated in the umbilical cord, sug-
gesting that they were translocated from the mother to
the fetus during pregnancy (Matamoros, Gras-Leguen,
Le Vacon, Potel, & de La Cochetiere, 2013). More recent
attempts to replicate these findings have not always
been successful, however, and some researchers have
argued that the bacterial presence in the placenta could
be caused by contamination of the sample rather than
translocation from mother to baby (de Goffau et  al.,
2018). Regardless, the microbiome of a pregnant woman
experiences several pronounced changes throughout
gestation that can affect the fetus. Specifically, there is
a decrease in proinflammatory bacteria and an increase
in anti-inflammatory bacteria from the first to third tri-
mester, as well as a massive proliferation of bacteria
that expertly assist in nutrient uptake (Koren et  al.,
2012; Mueller, Bakacs, Combellick, Grigoryan, &
Dominguez-Bello, 2015). This trajectory of microbial
development is an example of how bacteria respond
to the physiological needs of the host and aid in the
safe delivery and development of the baby.
Psychological factors also have an important effect
on the microbiome during pregnancy. Maternal stress
in particular influences both the microbiome of the
mother as well as the fetus. For example, the self-
reported stress of mothers during pregnancy—as mea-
sured by the Pregnancy-Related Anxiety Questionnaire
(PRAQ-R; Van den Bergh, 1990) and the reported fre-
quency of pregnancy-related hassles—predicted dif-
ferential gut microbiota in infants as well as their
susceptibility to GI disease and allergic reactions
(Zijlmans, Korpela, Riksen-Walraven, de Vos, & de
Weerth, 2015). Maternal stress has also been positively
correlated with the prevalence of bacteria associated
with respiratory symptoms, HPA reactivity (Golubeva
et al., 2015), and the disruption of amino-acid profiles
in the developing brain ( Jašarević, Howerton, et  al.,
2015). One possible mechanism of action is that emo-
tional and physiological stress influence the microbial
population of the vagina, decreasing commensal and
increasing pathogenic bacteria, which then seed the
infant’s microbiome as it passes through the birth canal
( Jašarević, Howerton, et al., 2015).
A variety of behavioral factors are also known to
affect the infant microbiome. For example, the mode
of delivery (vaginal vs. cesarean section), the location
of delivery (hospital vs. home birth), whether caregivers
breastfeed or provide the infant with formula, and
whether mothers and babies receive any type of anti-
biotic treatment early in life all have a lasting impact
on the microbiome. Infants born vaginally tend to have
microbiomes dominated by Lactobacillus strains from
their mothers’ vaginas and fecal matter (Dominguez-Bello
et al., 2010; Mueller, Bakacs, et al., 2015; Vaishampayan
et al., 2010), whereas the microbiomes of infants born
Microbes and the Mind 405
via caesarian section are largely populated by bacteria
found on the skin and immediate external environment—
such as the room in which the baby was delivered
(Dominguez-Bello et al., 2010). Relative to their formula-
fed counterparts, infants that are breastfed exhibit a
healthy population of Bifidobacterium and Lactobacil-
lus species (Fernández et al., 2013; Jiménez et al., 2012).
These bacteria can enhance the ability to uptake and
process nutrients (M. S. Kramer et  al., 2008; Roger,
Costabile, Holland, Hoyles, & McCartney, 2010), which
may in turn lead to positive neurodevelopmental out-
comes (e.g., improved intelligence and cognitive abili-
ties; M. S. Kramer et al., 2008). Last, the administration
of antibiotics during gestation and infancy is robustly
associated with decreased bacterial diversity—including
and especially the depletion of beneficial bacteria
(Mueller, Whyatt, et al., 2015). Although bacteria colo-
nies may repopulate eventually, massive bacterial extinc-
tion during these critical periods of development may
have long-term deleterious effects on a range of neuro-
logical and psychological outcomes.
Adolescence and early adulthood
Adolescence is a transitional period characterized by
major neuroanatomical changes that can partly be
mapped onto the developmental changes observed in
bacterial populations. For example, two of the most
critical alterations in the human cortex during late
childhood/early adolescence involve axonal myelina-
tion and synaptic pruning. Research with germ-free
animals has implicated bacteria in both of these pro-
cesses. Specifically, animals bred without a microbiome
show hypermyelination in the prefrontal cortex (Hoban
et al., 2016) as well as defective microglia cells (Erny
et al., 2015), which are crucial for pruning back neurons
during development (Paolicelli et  al., 2011; Schafer
et al., 2012). Of course, the disruption of neurological
development during adolescence as a result of bacterial
imbalances will likely have adverse consequences for
concomitant cognitive developments, and several
experimental studies offer supporting evidence. For
example, infecting healthy rodents with harmful bacte-
rial strains can lead to learning deficits (Gareau et al.,
2011; Li et al., 2009), whereas administering healthy bac-
teria to infected mice can ameliorate symptoms of cogni-
tive dysfunction (Bercik, 2011; Gareau, Jury, MacQueen,
Sherman, & Perdue, 2007).
As mentioned throughout this review, environmental
and psychological stressors alter people’s microbiota,
and adolescence is a developmental period rife with
these types of assaults. Changes in diet, disrupted sleep
patterns, access to drugs and alcohol, and navigating
sexual relationships all influence the microbiome, and
all typically have onsets during adolescence (De Filippo
et al., 2010; Iyer & Vaishnava, 2016; Mutlu et al., 2009).
Thus, adolescence is a stage during which neurological,
biological, social, and bacterial changes all unfold in
concert with one another in a manner that ultimately
sets the stage for healthy or pathological development
well into adulthood.
Aging populations and older adults
By 2030, people over the age of 60 years will outnum-
ber children under the age of 9 years, and by 2050,
there will be more people over the age of 60 years than
people between the ages of 10 and 24 years (United
Nations, 2015). Although this area of research is in its
nascent stages, physiological processes in these older
adult populations are especially likely to be connected
to the microbiome. For example, inflammation worsens
as the body ages (Guigoz, Doré, & Schiffrin, 2008), and
bacteria play an important role in regulating immune
responses at the systemic and molecular level. In addi-
tion, gut motility decreases as individuals age, leading
to changes in nutrient uptake, extended digestion times,
and irregularity in bowel movements (Camilleri, Lee,
Viramontes, Bharucha, & Tangalos, 2000). All of these
changes affect the composition of the microbiome and
the proportion of bacteria colonizing people’s intes-
tines. Although seemingly trivial, chewing strength may
also decline with age, which can change the integrity
and type of food the intestines are challenged to digest
(Watanabe, 1998). This can lead to different and pro-
longed functional demands on the bacteria tasked with
decomposing the food and extracting appropriate nutri-
ents. Medication regimens as people age may include
the prolonged use of antibiotics, which dramatically
influence bacteria populations. For all of these reasons,
the gut microbiota of human adults approximately 70
years of age and older is significantly different from
that of younger adults and infants (O’Toole & Claesson,
2010). Specifically, researchers have observed a decline
in the bacterial diversity of older human populations
(70–99 years old), and, not surprisingly, this decline
was comorbid with decreases in brain weight, brain
volume, and cognitive impairments (Biagi et al., 2010,
2013; Claesson et al., 2012).
Critical windows and sensitive periods
Microbial and neurological development unfold
together and thus may have overlapping windows of
time during which they are more or less responsive to
change and intervention. Specifically, emotional and
physiological stress during early life have a substantial
impact on both the brain and microbiome, and disrup-
tions may be difficult to normalize if interventions are
applied too late in development. For example, colonizing
406 Smith, Wissel
mice with commensal bacteria shortly after birth cor-
rected deficits in the development of the HPA axis
caused by restraint stress, whereas colonizing mice later
in life did not produce the same therapeutic outcomes
(Sudo et al., 2004). Likewise, deficits in social-cognitive
processes in mice established early in life (because of
an absence of key bacterial populations) could not be
reversed by bacterial interventions later in life (post-
weaning), although some behaviors (such as social
avoidance) were more amenable to treatment (Desbonnet
et al., 2014).
Adolescence may also constitute a sensitive devel-
opmental period. For example, bacterial profiles were
significantly altered in rats exposed to exercise during
their juvenile years, whereas exercise exposure during
their adult years showed no such effect. Furthermore,
the exercise-induced changes in the microbiota of these
adolescent rats were associated with an increase in lean
body mass (Mika et al., 2015), suggesting that earlier
(but not later) exercise-related interventions may facili-
tate the development of a microbiome that promotes
healthy weight maintenance. Likewise, colonization
with commensal bacteria during the adolescent period
reversed stress hyperresponsivity in mice (i.e., reversed
the prolonged elevation of adrenocorticotropin, or
ACTH, after a stressful event). However, bacteria colo-
nization introduced in later adulthood seemed to be
ineffective at ameliorating these stress-induced eleva-
tions in ACTH (Neufeld, Luczynski, Oriach, Dinan, &
Cryan, 2016). These findings suggest that early adoles-
cence is another critical window of development during
which gut bacteria can shape the stress response.
It is important to note that despite having sensitive
periods of development, the microbiome may be more
flexible across the life span and more amenable to
change than other physiological systems. Researchers
are currently examining a variety of restorative inter-
ventions geared toward transforming the microbiome
after it has been altered by early-life stress and assault
(Cowan, Callaghan, & Richardson, 2016; Mueller,
Bakacs, et al., 2015; Salazar et al., 2014). Several pre-
clinical bacteria-based treatments are being investigated
for their therapeutic and medical properties (Dinan,
Stanton, & Cryan, 2013). Indeed, the microbiome may
offer a pathway to correct neurodevelopmental patholo-
gies by acting on elements that influence function and
process (e.g., neurochemicals excreted by bacteria)
rather than relatively unalterable morphological struc-
tures (e.g., brain tissue).
Clinical Psychology and Psychopathology
Studies in humans and animals have repeatedly shown
that the microbiome is implicated in a variety of
psychopathological conditions. In fact, applied clinical
researchers were among the first psychological scien-
tists to collaborate with microbiologists to understand
the ways in which pathologies of the gut were comor-
bid with pathologies of the brain and behavior. This
section provides a brief overview of some of the most
frequently studied clinical conditions that sit at the
intersection of psychological and microbial processes
(for extensive reviews, see R. T. Liu, 2017; Nowakowski
et al., 2016).
Autism spectrum disorder
The microbiome has recently been placed at the fore-
front of autism spectrum disorder (ASD) research, and
although the role of the microbiome in ASD has enough
complexity for its own review article (see Luna, Savidge,
& Williams, 2016), some general conclusions can be
summarized here. Germ-free mice show similar social
deficits and repetitive behaviors as those observed in
humans with ASD (Desbonnet et al., 2014), and mouse
models of ASD have an altered microbiota (de Theije
et al., 2014), suggesting that when beneficial bacteria
are missing ASD-like deficits can appear. Because ASD
is so diverse and heterogeneous in nature, it is difficult
for specific microbiota-related findings to generalize
across the entire spectrum (as addressed in Song, Liu,
& Finegold, 2004). Despite this limitation, some findings
do have more general implications for ASD. For exam-
ple, rates of GI pathologies and symptoms are dispro-
portionately high in people with ASD compared with
neurotypical populations (de Theije et al., 2011). Pro-
biotics, prebiotics, and antibiotics have all shown
behavioral benefits for people with ASD (Critchfield,
van Hemert, Ash, Mulder, & Ashwood, 2011; Grimaldi
et  al., 2018), but whether this is due to the bacteria
themselves or the natural cycle of ASD is still unclear.
All of these findings do, however, suggest that a base-
line dysbiotic state may exist in those with ASD.
Clinical depression and anxiety
There has been an abundance of research on the ways
in which the microbiome shapes depression and anxi-
ety (for recent and thorough reviews, see Foster &
Neufeld, 2013; Huang, Wang, & Hu, 2016). However,
most of this work has been conducted with rodents
rather than humans. Nonetheless, some recent research
in humans has found that depression and anxiety symp-
toms increase stepwise as GI symptoms and severity
increase (Pinto-Sanchez et al., 2015). GI illness is also
highly comorbid with clinical depression and anxiety
(Maes, Kubera, Leunis, & Berk, 2012; Maes et al., 2013).
In addition, probiotics have been found to improve
Microbes and the Mind 407
both GI and clinical depression and anxiety symptoms
for those with disorders such as irritable bowel syn-
drome (Pinto-Sanchez et  al., 2017; Wallace & Milev,
2017). Although under some circumstances probiotics
can have antidepressant or anxiolytic effects robust
enough to relieve clinically classified symptoms in
humans, how this happens and which combination of
probiotics may be most optimal for treatment requires
further investigation.
Posttraumatic stress disorder
The microbiome is implicated in both the normative
and hyperactivated stress response in humans (R. T.
Liu, 2017) and animals (e.g., van de Wouw et al., 2018).
Given that severe and prolonged stress is a central
feature of posttraumatic stress disorder (PTSD),
researchers have begun to explore the ways in which
the microbiome is related to the prevalence and time
course of this disorder (Malan-Muller et al., 2018). For
example, in a recent exploratory study researchers
reported that individuals with a PTSD diagnosis had
lower proportions of three distinct phyla of bacteria
(Actinobacteria, Lentisphaerae, and Verrucomicrobia)
compared with controls who had also been exposed to
a traumatic event but did not meet the clinical threshold
for a PTSD diagnosis. In addition, increased scores on
the Clinician-Administered PTSD Scale (CAPS-5;
Weathers et al., 2013) were associated with decreases
in the three bacterial taxa (Hemmings et al., 2017).
Developing future clinical treatments
In addition to the topics reviewed above, clinical
research has also been conducted on how the micro-
biome may be associated with many other challenges
related to physical and mental health, including chronic
fatigue syndrome ( Jackson, Butt, Ball, Lewis, & Bruck,
2015; Rao et  al., 2009), anorexia (Armougom, Henry,
Vialettes, Raccah, & Raoult, 2009), alcoholism (Engen,
Green, Voigt, Forsyth, & Keshavarzian, 2015; Mutlu
et  al., 2009; Yan & Schnabl, 2012), schizophrenia
(Severance, Yolken, & Eaton, 2016), and manic depres-
sion (Dickerson, Severance, & Yolken, 2017; Kanji et al.,
2018). It is clear from this wide range of examples that
factors that affect the microbiome are relevant to physi-
cal and mental health. Exactly which mechanisms are
at play, how these mechanisms operate, and what route
may be most optimal for treatment is still being debated,
but it seems that the administration of probiotics has
the strongest impact on behavioral change. Live bacte-
ria that, when administered in a clinical or medical
context, have a significant beneficial effect on the host
have been termed psychobiotics (Bambury, Sandhu,
Cryan, & Dinan, 2018; Dinan et  al., 2013; Misra &
Mohanty, 2017; Wall et al., 2014). Although there is still
a need for more randomized, controlled, clinical trials
investigating the impact of psychobiotics on humans
(Anglin, Surette, Moayyedi, & Bercik, 2015), their thera-
peutic potential for a broad range of mental-health
experiences is a promising future direction for pharma-
cologically driven treatments.
Pathways of Communication: Connecting
the Mind and Gut via the Vagus Nerve
Microbiologists are beginning to home in on which
biological structures may facilitate communication
between the gut and the brain. A promising and pri-
mary contender is the vagus nerve—a component of
the autonomic nervous system that has been of special
interest to psychological scientists investigating social
emotions (Muhtadie, Koslov, Akinola, & Mendes, 2015;
Quintana, Guastella, Outhred, Hickie, & Kemp, 2012;
Shahrestani, Stewart, Quintana, Hickie, & Guastella,
2015), subjective well-being (Geisler, Vennewald,
Kubiak, & Weber, 2010), mindfulness (Kok et al., 2013;
Svendsen et al., 2016), health (Thayer, Åhs, Fredrikson,
Sollers, & Wager, 2012), and psychopathology (Austin,
Riniolo, & Porges, 2007; Patriquin, Scarpa, Friedman, &
Porges, 2013). Indeed, there may be no other discipline
outside the biological sciences that has examined the
influence of the vagus nerve on cognitive, social, and
emotional outcomes as widely as psychological science.
This suggests, therefore, that psychological scientists
may be uniquely positioned to help microbiologists
answer questions that sit at the intersection of psycho-
logical, microbial, and vagal processes.
Why are microbiologists interested in
the vagus nerve?
The vagus nerve plays a central role in conveying infor-
mation about the state of the GI tract, as well as other
organs, to the CNS, with approximately 20% of its fibers
dedicated to GI–CNS communication (Forsythe,
Bienenstock, & Kunze, 2014; Stakenborg, Di Giovangiulio,
Boeckxstaens, & Matteoli, 2013). Note that certain bac-
teria that have colonized the gut may only be capable
of exerting effects on mental and neurological pro-
cesses if the vagus nerve is functionally intact. That is,
the vagus nerve may constitute a direct line of com-
munication between bacteria and the brain. Microbiolo-
gists have reached this conclusion after conducting
multiple studies demonstrating that surgically severing
the vagus nerve eliminates, or in some cases reverses,
both the positive psychological effects of commensal
408 Smith, Wissel
bacteria and the negative psychological effects of
pathogenic bacteria. For example, severing the vagus
nerve of mice eliminated the antianxiety effects of at least
two species of commensal bacteria—L. rhamnosus (Bravo
et al., 2011) and B. longum (Bercik, Park, et al., 2011)—as
well as the antidepressant effects of L. rhamnosus (Bravo
et al., 2011). Likewise, when mice were colonized with
pathogenic bacteria, severing the vagus nerve pre-
vented maladaptive behavior from emerging, whereas
administering pathogenic bacteria to mice with intact
vagus nerves led to increased anxiety-like behaviors
(Bercik, Park, et  al., 2011). Taken together, there is
compelling preliminary evidence that one process by
which bacteria influence psychological outcomes
depends, at least in part, on vagal integrity.
Vagal influence on psychological
outcomes
Over the past 20 years, psychological scientists have
implicated the vagus nerve in a range of psychological
outcomes that are related to those currently being
examined by microbiologists. For example, in human
subjects, higher heart-rate variability (a measure of
healthy vagal functioning) is associated with lower lev-
els of trait anxiety (Svendsen et al., 2016) as well as a
more habitually positive mood (e.g., cheerfulness,
calmness), higher life satisfaction (Geisler et al., 2010),
and more competent social communication (Quintana
et  al., 2012; Shahrestani et  al., 2015). People with
greater vagal flexibility (another measure of adaptive
vagus nerve functioning) exhibit more accurate percep-
tions of social-emotional cues and are more sensitive
to their social context (Muhtadie et  al., 2015). In a
longitudinal intervention-based study designed to
improve psychological well-being, individuals who had
higher baseline vagal tone (an index of both vagal and
cardiovascular health) showed significantly larger
increases in positive emotions compared with individuals
who had low vagal tone (Kok et al., 2013). Furthermore,
researchers have found that vagus nerve stimulation can
reduce symptoms of depression and anxiety and point
to the gut–brain axis as an important mechanism of
action (Kong, Fang, Park, Li, & Rong, 2018).
Psychological scientists have thus repeatedly dem-
onstrated that there is a link between the vagus nerve
and emotion, cognition, and behavior, whereas micro-
biologists have demonstrated that the vagus nerve
mediates the relationship between bacterial communi-
ties and these same outcomes. Psychological scientists
have often situated their findings in the context of
broader physical health (e.g., HPA reactivity), and given
the overlap between psychological and microbial out-
comes outlined above, it may be a particularly
appropriate and fruitful time to begin considering how
the bacteria that people share their bodies with interact
with the vagus nerve and, in turn, influence outcomes
of great interest to psychological science.
Other pathways of bacteria-brain
communication
Researchers are also beginning to identify several addi-
tional mechanisms by which the microbiome influences
neurological and psychological outcomes (see Fig. 1;
for a detailed and accessible review, see Wiley et al.,
2017). For example, bacterial communities can interface
with the CNS by excreting metabolites with neuromodu-
latory properties and release hormone-signaling pep-
tides in the intestines that act on both sympathetic and
parasympathetic pathways (Schele et al., 2013; Wren &
Bloom, 2007). Different species of bacteria are also
capable of interacting with the immune system at the
molecular level, resulting in changes to the circulation
of pro- and anti-inflammatory cytokines that influence
CNS functioning (Dantzer, 2009; Dinan & Cryan, 2017;
Petra et al., 2015). Furthermore, dysbiosis or an over-
growth of pathogenic bacteria can lead to increased
permeability of both the intestinal lining (e.g., “leaky
gut”; Hollander, 1999) and the blood-brain barrier
(Logsdon, Erickson, Rhea, Salameh, & Banks, 2018),
accelerating the rate and proportion of microbial infil-
tration (de Theije et  al., 2011). As the science of the
gut–brain axis advances, microbiologists, neuroscien-
tists, immunologists, and medical professionals will
continue to uncover more detail concerning these path-
ways of communication—and psychological scientists
motivated to deeply understand the mind-body con-
nection will undoubtedly have important contributions
to make.
Practical Applications and Future
Directions
There is meaningful overlap in the topics psychological
scientists and microbiologists have been studying, but
research exploring these topics has largely taken place
in parallel rather than as interdisciplinary collabora-
tions. There are, however, a few notable exceptions that
illustrate the important role psychological scientists can
play in advancing work on how bacteria shape mental
states. For example, Callaghan and colleagues have
integrated microbiology into their groundbreaking
work on intergenerational stress in rodents, demonstrat-
ing that the toxic effects of stress brought on by early-
life adversity (such as maternal or paternal separation)
can be ameliorated by probiotic interventions (Callaghan,
Cowan, and Richardson, 2016; Callaghan, 2017). This is
Microbes and the Mind 409
in line with recent research by microbiologists demon-
strating that microbiota can both cause or reduce stress
depending on the type and ratio of bacteria present in
people’s bodies and that it is a key regulator of the
stress response (i.e., HPA reactivity, the release of glu-
cocorticoids; self-reported or subjectively experienced
stress; Wiley et al., 2017). In fact, microbiologists have
already undertaken quite a bit of work demonstrating
that bacteria influence the experience of stress in a
variety of contexts relevant to psychological scientists
such as academic pressure (Kato-Kataoka et al., 2016;
Nishida et  al., 2017) and familial disruptions such as
maternal separation ( Jašarević, Rodgers, & Bale, 2015;
Waworuntu et  al., 2017). Yet collaborations between
microbiologists and psychological scientists on this
topic are rare, despite the fact that they would almost
certainly enrich our understanding of the microbiome
and stress in ways neither field could accomplish alone.
Another area of research in which psychological sci-
entists may fruitfully integrate microbial measures is
work on Gene × Environment interactions. Recent
reports confirm that most genes in the human body do
not belong to the human genome but rather to the col-
lective bacterial genome (Qin et al., 2010). In addition,
human and microbial genes interact regularly and recip-
rocally to influence each other’s expression and, there-
fore, function (Bordenstein & Theis, 2015; Fellows
et al., 2018; Theis et al., 2016). This has important and
possibly dramatic implications for the ways in which
psychological scientists study Gene × Environment
interactions. Consider, for example, the work of Tucker-
Drob and colleagues reporting that outcomes such as
cognitive ability, intelligence, and academic achieve-
ment are shaped by interactions between genetic fac-
tors and socioeconomic status (Tucker-Drob & Bates,
2016; Tucker-Drob & Harden, 2012; Tucker-Drob,
Rhemtulla, Harden, Turkheimer, & Fask, 2011). We now
know, of course, that the microbiome is related to each
of these variables, but perhaps most important is the
degree to which socioeconomic status (the environ-
mental factor) influences the microbiome through path-
ways such as diet, sanitation opportunities (e.g., clean
water, clean air), and access to green space. Researchers
could thus predict that a meaningful source of vari-
ability in these types of Gene × Environment interac-
tions is accounted for not only by how the environment
affects the human genome but also by how it affects
each individual’s microbial genome.
One limitation of the extant work exploring
microbe–host interactions is that it has predominantly
been conducted with nonhuman models. This can make
it difficult to generalize findings across species, despite
relevant similarities (e.g., pathological symptoms are
overrepresented in both human and rodent males, and
both are naturally inclined toward social interaction
and stability; Desbonnet et  al., 2014). Psychological
scientists now have the opportunity to test generaliz-
ability as well as explore the subjective mental states
that are associated with physiological and behavioral
outcomes. Take, for example, a common behavioral
paradigm used with rodent models: the forced swim
test (FST). The FST involves placing a rodent in a con-
tainer of water with smooth surfaces so that it must
either actively swim or passively float. Depending on
the research hypotheses, the outcome of interest may
be time spent swimming (a proxy for perseverance) or
time spent immobile (a proxy for depression). Creating
appropriate human analogs for such behavioral mea-
sures and augmenting them with self-reports of intero-
ceptive, emotional, and cognitive states may provide
useful insight into how bacteria influence conscious,
psychological perceptions rather than simply modulate
innate behavioral action plans.
Psychological scientists are well positioned to har-
vest a variety of low-hanging fruit simply by investigat-
ing how bacteria influence the areas of research in
which they are the experts, and now is the time to start.
A rapidly increasing number of programs are already
collecting microbiome-related information from a stag-
gering number of participants thanks to large-scale ini-
tiatives at both the national and international level. For
example, the National Institutes of Health, National
Science Foundation, National Aeronautics and Space
Administration, Department of Energy, and Department
of Agriculture recently announced a generously funded
collaboration called the National Microbiome Initiative.
This initiative aims to expand interdisciplinary research
on the microbiome and includes the support of more
than 100 external institutions across the private sector
and academia (White House Office of Science and
Technology Policy, 2016). In addition, dozens of citizen-
scientist projects such as uBiome and Your Private
Biome have transformed the swelling public interest in
the microbiome into an interactive scientific effort in
which thousands of everyday people share their micro-
biome data with scientists, and scientists in turn have
access to highly powered, incredibly diverse data sets
for analyses and exploration. Although breaking into
the microbial world may be intimidating for the nonmi-
crobial scientist, the relationship between microbes and
the mind cannot fully be understood if the perspectives
and expertise of psychological scientists remain absent.
Action Editor
June Gruber served as action editor and interim editor-in-chief
for this article.
410 Smith, Wissel
Author Contributions
E. F. Wissel and L. K. Smith are co-first authors and con-
tributed equally to this work. Both authors approved the
final manuscript for submission.
ORCID iD
Emily F. Wissel https://orcid.org/0000-0003-2275-8456
Acknowledgments
We thank Timothy Loving for his feedback on this manuscript
and for always being supportive of our research ambitions.
Declaration of Conflicting Interests
The author(s) declared that there were no conflicts of interest
with respect to the authorship or the publication of this
article.
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