Selhub et al. Journal of Physiological Anthropology 2014, 33:2
http://www.jphysiolanthropol.com/content/33/1/2

REVIEW

Open AccessFermented foods, microbiota, and mental health:ancient practice meets nutritional psychiatry
Eva M Selhub1*†, Alan C Logan2† and Alison C Bested3†

Abstract
The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability,
nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages
continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledgeof the human microbiome increases, including its connection to mental health (for example, anxiety anddepression), it is becoming increasingly clear that there are untold connections between our resident microbes andmany aspects of physiology. Of relevance to this research are new findings concerning the ways in whichfermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals(for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids)
may act upon our own intestinal microbiota profile. Here, we argue that the consumption of fermented foods may
be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. The
extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least
to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the
specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental
health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteria species)
associated with fermented foods may also influence brain health via direct and indirect pathways.

Introduction‘The processes required for fermented foods were
present on earth when man appeared on the scene…
When we study these foods, we are in fact studying themost intimate relationships between man, microbe
and foods.’ [1]Prof. Keith H. Steinkraus, Cornell University, 1993
As highlighted in the quotation, our Paleolithic ancestors
had plenty of opportunity for the consumption of foodproducts (for example, honey, fruits or berries, and theirjuices) that had been unknowingly subjected to natural
microbial fermentation. Without knowledge of microbes,
our ancestors recognized, over time, the palatability, preservative, analgesic, and mentally stimulating or sedating* Correspondence: eselhub@partners.org†
Equal contributors
1
Harvard Medical School and Massachusetts General Hospital, 40 Crescent St.,
Suite 201, Waltham, MA 02453, USA
Full list of author information is available at the end of the article

qualities of fermented foods and beverages [2]. Thus, thestage was set for the purposeful application of fermentation
to provide value in the areas of human nutrition, traditional
medicine, and culture (ceremonies, and so on) [3,4]. It isdifficult to say with certainty when intentional fermentation
began in earnest; however, sophisticated measurementsof the chemical content within ancient Neolithic vessels
suggest intentional fermentation of fruit, rice, or honeybeverages has been in common practice for close to
10,000 years [5]. As agriculture expanded, so too did
intentional fermentation techniques. Beyond the clear
references to alcohol production, it is now obvious thathousehold and artisanal fermentation of cereals, dairy,
vegetables, fish, seafood and meats were a significant partof ancestral dietary practices [6].
Modern advances in chemical preservation, refrigeration,and transportation efficiency have not resulted in theabandonment of fermented foods. At least in traditional
dietary practices, fermented foods and beverages remainwidespread, currently accounting for approximately onethird of the human diet globally [7]. Moreover, as scientists
continue to uncover health-promoting properties of© 2014 Selhub et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

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ancestral dietary patterns (for example, the Mediterraneandiet, the traditional Japanese diet, and hunter-gatherer
diets), by extension there is a renewed examination of thefermented foods that are so often a part of such ancient
diets [8]. Emerging research, as reviewed here, indicatesthat fermentation may magnify the known benefits of awide variety of foods and herbs, influencing the bioavailability and activity of the chemical constituents. In addition,as our knowledge of the human microbiome increases(the intestinal microbiota in particular), it is becoming
increasingly clear that there are untold connections between the ways in which microbes act upon dietary items
pre-consumption, and in turn, the ways in which thesefermented dietary items influence our own microbiota.
Here, we review and synthesize various lines of investigation related to fermented foods, intestinal microbiota,
and mental outlook. We argue that the consumption of
fermented foods may be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. It is our contention that fermentation
may amplify the specific nutrient or phytonutrient content
of foods, the ultimate value of which is associated withmental health; furthermore, we also argue that the
microbes associated with fermented foods may also
influence brain health via direct and indirect pathways.

Traditional diets and mental health
The shift away from traditional lifestyles has been linked
to increased rates of depression and other mental healthdisorders [9-11]. Among the variables that might afford
protective or resiliency effects against mental health disorders (depression in particular), diet has emerged as at least
one strong candidate [12]. Superficially, it would seem obvious, given the brain’s dependence upon nutrients for its
structure and function (including the micronutrients andnon-nutrient dietary antioxidants, for example polyphenols,
that run the antioxidant defense system) that nutrition
should be a target of research in mental health. Remarkably,
this area of research, now known as nutritional psychiatry,is one that has been historically neglected or the subject ofpoorly designed studies. However, there have been tremendous strides in recent years and the research connecting
mental health and nutrition has become increasingly robust. Indeed, a recent 5-year prospective study (n = 23,020)
has shown that unhealthy maternal and early postnatal
dietary patterns (for example, processed and refined foods,
high-sugar beverages, high-sodium snacks) elevate the riskof behavioral and emotional problems in children [13].
Traditional dietary practices, often exemplified byMediterranean and Japanese models, are typically characterized by (relative to Western practices) higher intakes offruits and vegetables, fish and seafood, cereals with limited
processing, fiber, and only modest amounts of dairy andlean meats [14]. A variety of population studies have linked

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adherence to traditional dietary patterns with lowered riskof anxiety or depression [15-20]. Among the more convincing of these studies are the recent prospective investigations showing that stronger adherence to traditional
healthy dietary patterns is associated with a 25 to 30%
lower risk of depression [16,17]. Traditional Japanese
dietary practices, where fermented soy products are specifically linked to adherence, have also been associatedwith lower rates of depressive symptoms [21,22]. Alcohol
has deservedly received much attention in the link
between problematic consumption and a higher riskof depression. However, when consumed in modest
amounts (5 to 15 g per day) as part of traditional dietary practices, alcohol (red wine in particular) has been
associated with a lower risk of depression [23]. Indeed,light to moderate alcohol consumption has been associated with lower systemic inflammation, a finding notevident in those with depression [24].
Epidemiological studies show that there exists an elevated risk of depressive symptoms in healthy adults withblood chemistry indicative of insulin resistance [25].
Depressive symptoms correlate with higher fasting andstimulated glucose levels, even in the absence of an association with adiposity in adolescents at risk of type II diabetes[26]. This is of relevance when viewed along with a rapidly
growing body of research highlighting the type-II-diabetes
protective properties of traditional dietary practices [27]. As
we will discuss, the intestinal microbiota, via a number of
mechanisms, may play a role in mediating the glycemic andmood related effects of the Western dietary pattern [28].
Specific items within traditional dietary patterns havebeen individually associated with protection against depression and, experimentally, these components have also
demonstrated antidepressant properties. Examples include,
but are not limited to soy foods, turmeric, cocoa, green tea,coffee, blueberries, pomegranate, and honey. The isolated
polyphenols and other phytochemicals within these foods
have also been documented to provide antidepressive properties in experimental models [29-38]. In addition, specificnutrients such as magnesium, zinc, vitamin C, folic acid, andvitamin B12, have also been connected to resiliency against
depression or improvement in depressive symptoms [39-42].
The mechanisms by which required nutrients, such as
the aforementioned vitamins and minerals, influencemood can be explained in part by their role in the production of neurotransmitters [43]. However, the connection
between mood and non-essential dietary components(for example, phytochemicals) has been the subject ofintense scrutiny; their role in the antioxidant defense system as well as their ability to provide anti-inflammatory
support appears to be at play [44]. Advances in the understanding of the pathophysiology of mood and anxiety
disorders have provided a more complete picture of theinducing role played by the tandem of oxidative stressSelhub et al. Journal of Physiological Anthropology 2014, 33:2
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and low-grade inflammation. Elevations in markers ofinflammation (for example, cytokines, C-reactive protein),and overwhelm of the normal antioxidant defense system,
are no longer dismissed as mere consequence in emotional
disorders [45]. The burden of oxidative stress and inflammation is emerging as a viscous cycle that can directly influence mood, and the combination of the two appears to
be both a cause and a consequence of depression [46,47].
When levels of body-wide inflammatory cytokines areelevated, they can subsequently signal the production of
inflammatory cytokines within the central nervous system
via microglia activation. Chronic activation of microglia
can compromise neuronal functioning by setting in motion a cascade of further inflammation and oxidative stress[48]. The end result may manifest as compromised intra
and extracellular neuronal communication.

Inflammation and mood pathways
In this exciting area of research, one of the open questions
is how chronic inflammation might be initiated and maintained in illnesses such as depression, and what the gut has
to do with this. Emerging studies show that the normallyvery selective intestinal barrier may be compromised indepression (and in numerous conditions where depression
is often a hallmark symptom) [49-56]. Psychological stressand exhaustive exercise have been shown to increase thepermeability of the intestinal barrier [57-59]. However,a Westernized diet high in fat and sugar has also beenshown to cause a more porous intestinal lining, the consequences of which include systemic access to food antigens,environmental toxins, and structural components of
microbes, such as lipopolysaccharide endotoxin (LPS)[60]. The latter agent, LPS, is particularly important regarding depression; even relatively small elevations in systemic
LPS levels have been shown to provoke depressive symptoms and disturb blood glucose control [61-67]. Endotoxins
such as LPS can decrease the availability of tryptophan
and zinc, thereby negatively influencing neurotransmission[68,69]. Moreover, systemic LPS can elevate inflammationand oxidative stress. Traditional dietary practices havecompletely divergent effects of blood LPS levels; significant reductions (38%) have been noted after a one-monthadherence to a prudent (traditional) diet, while theWestern diet provokes LPS elevations [70]. These andother findings help establish mechanisms whereby the
LPS-lowering, antioxidant, and anti-inflammatory properties of broad traditional dietary practices, as well as specific components within them, can help provide moodsupport. Indeed, when the limitation of intestinal absorption is overcome, individual phenolic structures have beenshown, at least experimentally, to curb the breakdown ofcentral neurotransmitters, mimicking the proposed mechanistic properties of some primary antidepressant medications [71,72]. As we will discuss, enhanced bioavailability

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via fermentation may therefore be an important factor infood (or herbs) as medicine.

Microbiota and mental health
Related to the differences in traditional versus contemporary Westernized dietary patterns and mental health is therole of the intestinal microbiota. A decade ago, prior to thescientific hypotheses of Logan et al. [73,74], the notion thatthe intentional manipulation of the intestinal microbiota
could provide therapeutic value to human depressive andfatigue states was, at the very least, outlandish. However, inthe ensuing years, many of the mechanisms first proposed
by Logan and colleagues (as listed, adapted from [73,74])
whereby beneficial microbes could influence mood orfatigue, have been examined experimentally.
 Direct protection of the intestinal barrier; Influence on local and systemic antioxidant status,

reduction in lipid peroxidation;
 Direct, microbial-produced neurochemical production,for example, gamma-aminobutyric acid (GABA); Indirect influence on neurotransmitter orneuropeptide production;
 Prevention of stress-induced alterations to overall

intestinal microbiota;
 Direct activation of neural pathways between gut

and brain; Limitation of inflammatory cytokine production;
 Modulation of neurotrophic chemicals, including

brain-derived neurotrophic factor;
 Limitation of carbohydrate malabsorption;
 Improvement of nutritional status, for example,






omega-3 fatty acids, minerals, dietary
phytochemicals;
Limitation of small intestinal bacterial overgrowth;
Reduction of amine or uremic toxin burden;
Limitation of gastric or intestinal pathogens(for example, Helicobacter pylori);
Analgesic properties.

Moreover, preliminary placebo-controlled human studies
have shown that oral probiotic microbes can decrease
anxiety, diminish perceptions of stress, and improvemental outlook [75]. In the context of our later discussionof fermented foods and their intersection with the gutbrain-microbiota connection, a brief summary of thismicrobiota-brain research is necessary. For interested
readers, more detailed reviews specific to the scientificadvances exploring direct and indirect relationships
between intestinal microbes and anxiety or depression
have recently been published [76,77].
Viewed strictly from the nutritional perspective, experimental studies have shown that the administration of probiotic bacteria to laboratory chow can increase peripheral

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tryptophan levels, and alter dopamine and serotoninturnover in the frontal cortex and limbic system [78].
In addition, probiotic-fortified laboratory chow increases
the tissue levels of omega-3 fatty acids [79], and theomega-3 fatty acids play a critical role in communicationin and between nerve cells. The consumption of omega-3
fatty acids, eicosapentaenoic acid in particular, has been
linked to positive mental outlook and reduction inmental distress in human beings [80]. Levels of otheranti-inflammatory fatty acids, such as gamma-linolenicacid, also increase in the human plasma when coadministered with probiotics [81]. It is also becoming
increasingly clear that the extent to which phytochemical
absorption can provide systemic antioxidant and antiinflammatory activity is controlled, at least to some degree,
by resident intestinal microbiota [82-84]. Finally, probiotics
and the overall profile of the intestinal microbiota can
influence tissue levels of mood-regulating minerals, suchas magnesium and zinc [85,86].
As mentioned, intestinal microbiota may also havefar-reaching effects related to glycemic control; our commensal gut microbes may contribute to healthy glucose tolerance. Indeed, the oral administration of Bifidobacterium
lactis, and, in separate research, the combination of
Lactobacillus curvatus and Lactobacillus plantarum,
can improve fasting insulin levels and glucose turnoverrates, even in the presence of a high-fat diet [87,88].
Again, the minimization of the detrimental LPS burden
by beneficial microbes appears to be a central mechanism in the promotion of normal glycemic control [89].
For example, bifidobacteria and other beneficial microbes
can prevent the efflux of LPS into systemic circulation,
while in human beings, the administration of probiotics
may diminish systemic access of gut-derived LPS and also
reduce reactivity to the endotoxin [90].
Beyond direct nutritional and glycemic effects, there
are other intriguing ways in which probiotics and theintestinal microbiota have been connected to the brain.
When a strain of Lactobacillus rhamnosus is administeredto healthy animals under stress, there is a reduction inanxiety and depression-like behaviors in experimental
models, such as the elevated plus maze and forced swim
tests. These behavioral changes were associated with alterations in the GABA system of the brain in the probiotic
group, matching the known effects of antidepressant or
anxiolytic chemical agents (for example, anxiolytic agents
such as benzodiazepines work at GABA receptors) [91].
Importantly, the changes in behavior and brain chemistry were largely extinguished with vagotomy, suggesting
direct lines of communication from gut to brain [90].
Additional research shows that Lactobacillus helveticus
and Bifidobacterium longum added to animal drinking
water can increase nerve cell resiliency and reduce apoptosis during conditions of experimental physiological stress

Page 4 of 12[92]. Moreover, oral Mycobacterium vaccae, a soil-based
microorganism widely distributed in nature, which caneasily find its way onto edible plants, has been shown inexperimental models to improve cognitive function anddiminish anxiety-like behavior among animals [93].
There are also a number of studies involving mice rearedin germ-free environments, the results of which seem todemonstrate a direct role of intestinal microbiota on behavior. Compared withconventional animals raised with thenormal range of intestinal microbiota, these animals display
the murine equivalent of what might be decreased anxiety[94-96]. Meanwhile, supplementation with Bifidobacterium
appears to attenuate an exaggerated stress response andmaintain adequate levels of the neuropeptide brain-derived
neurotrophic factor (BDNF), levels of which are known tobe low in depression [97]. It is also noteworthy that evenmild chronic inflammation of the gastrointestinal tract can
provoke anxiety and diminish BDNF production in animals[98]. Furthermore, supplementation with Bifidobacterium
also provides systemic protection against lipid peroxidation and decreases brain monoamine oxidase activity,
thereby potentially increasing intersynaptic neurotransmitter levels [99].
Rodent studies have provided compelling insights;
however, they have countless shortcomings as a reflectionof human microbiota, human dietary patterns, and theultimate intertwining of these variables with complex
mental health disorders. Far more convincing research,albeit very preliminary at this juncture, comes from published human studies involving probiotic administration.
The first formal investigation of a probiotic and humanmental outlook involved 132 otherwise healthy adults
consuming Lactobacillus casei fermented beverage forthree weeks; vs. placebo, significant improvement in moodscores were noted upon the among those with the higher
baseline depressive symptoms [100]. A separate placebocontrolled pilot study, one using the same Lactobacillus
casei probiotic (powder form), involved 39 chronic fatigue
syndrome patients. After two months, depression scoresremained unchanged between the groups, however Beck
Anxiety Inventory scores showed significant improvements
in anxiety versus placebo [101].
Michaël Messaoudi and colleagues from France evaluateda Lactobacillus helveticus and Bifidobacterium longum
combination probiotic, which was orally administeredfor one month (n = 55) in a placebo-controlled study[102]. Among the otherwise healthy adults, significant
improvements in depression, anger, anxiety, and lower
levels of the stress hormone cortisol versus placebo
were noted. A concurrent experimental arm of the study
also confirmed that the probiotic added to the dietary ofrodents was effective in reducing behaviors indicative ofanxiety. Messaoudi’s group performed a secondary analysis,
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free cortisol (n = 25). Indeed, the results once again
showed improvement with Lactobacillus helveticus andBifidobacterium longum versus controls (particularly
in somatization, depression and anger-hostility), andamong this low cortisol sub-group the overall benefits
in anxiety and depression were pronounced over time[103]. In addition, a study involving 44 patients with irritable bowel syndrome showed thatoral consumptionof a prebiotic fiber (trans-galactooligosaccharide) significantly reduced anxiety in conjunction with marked
elevations in fecal bifidobacteria levels [104].
Finally, a small placebo-controlled study involving functional magnetic resonance imaging (fMRI) has demonstrated that the one-month consumption of a fermented
food containing Bifidobacterium animalis subsp lactis,
Streptococcus thermophilus, Lactobacillus bulgaricus, andLactococcus lactis subsp lactis can influence brain activity
versus baseline [105]. Specifically, the researchers reported
that the group who received the fermented dairy product,versus unfermented counterpart and the no-intervention
controls, affected activity of brain regions that control
central processing of emotion and sensation. Enthusiasm
concerning this study runs high, with editorials in mainstream journals claiming that this fMRI study, ‘provides
the first objective evidence that gut commensal and/or
probiotic bacteria influence brain activity in healthy
humans’,[106]. The study, of course, did not provide any
such objective evidence concerning ingested bacteria; it
was a study involving a transformed milk product, not
an isolated probiotic powder. Despite attempts to keep
caloric and macronutrient content equal, a fermented
milk product is not the same as an unfermented milk
product in only its microbiota. Within the study, there
was no evidence of a change in gut microbiota profile via
consumption of the fermented product; however, more importantly, the fermentation of milk significantly alters bioactive peptides and other chemicals that are well capable ofinfluencing central nervous system function [107-110]. In
short, objective evidence that ingested probiotic bacteria
alone (or diet-induced shifts in commensal bacteria) can
influence human brain activity has yet to be published.

Traditional diets and microbiota
Before proceeding to make the case for a more focusedinvestigation of fermented foods for mental health, it isimportant to discuss the available research on traditional
dietary patterns and their ability to influence intestinal
microbiota. It is becoming increasingly clear that indigenous or traditional dietary patterns are directly inclusive of many bacterium species that might be considered
to have probiotic potential. Indeed, it is estimated that
35% of all lactic acid bacteria isolated from raw fruits andvegetables can survive gastric conditions [111]. The recent
study on the anti-anxiety effects of the soil microorganism

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Mycobacterium vaccae in animals [93] suggests that wewould do well to broaden our considerations of the classically defined beneficial microbes, that is, beyond that of
exclusively the Lactobacilli and Bifidobacteria genera.
One of the first studies examining the effects of traditional diet, 30 years ago, looked at differences in the fecal
microbiota of rural Japanese versus Canadian urbanites.
The researchers noted higher counts of Bifidobacterium
species and Lactobacilli in the rural Japanese, a group thatlargely maintained a traditional high-fiber diet rich infermented foods, vegetables, and fish. The investigators
used culture technique to examine the microbiota, anddespite its limitations as a means to reflect the overall
intestinal microbiome, there were some interesting findings. The amounts of Clostridia species in the Canadians
were higher, and overall there was greater biodiversity(more genera and species) in the rural-dwelling Japanese[112]. As discussed later, this has been the primary findingof more sophisticated contemporary studies using DNA
sequencing of stool samples, that is, there is more bacterial
diversity in those consuming traditional diets. In follow-up,
this research group reported on the differences in fecal
microbiota among older adults residing in Tokyo versus
elderly rural Japanese maintaining a high-fiber traditional
diet inclusive of fermented foods. The results again showed
higher numbers of Bifidobacterium species among therural dwellers and lower amounts of Clostridium species, Clostridium perfringens in particular [113].
Recent DNA techniques allow for a more broad evaluation of the intestinal microbiome as mediated by diet.
Researchers have shown significant differences in the
fecal microbiota of Western European children versus
rural African children living in an environment resemblingthat of our Neolithic ancestors. Overall, there were fewer
potentially pathogenic bacteria, and a far more diverse
range of microbes in rural Africans who maintain a
traditional lifestyle and consume traditional foods [114].
It is noteworthy that a variety of fermented foods are
consumed by those living in the rural African area
which was studied, and there are numerous lactic acidbacteria present on plant foods within this traditional
diet [115]. Separate work has uncovered distinct differences in microbial groups and their functional genes(for example, those governing metabolism of amino acids)
in US urban dwellers versus villagers living in Africa
and South America. Here again, the fecal microbiota of
US urbanites showed far less diversity than that of villagers in these distinct regions. Diet, rather than hygiene
per se, was reported to be the key spark for the development of intestinal microbiota structure [116]. Remarkably,
investigations of highly preserved human coprolites(ancient stool samples retrieved from archeological sites)
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traditional rural settlements than that of the contemporary urban dweller [117].
What then, are the broad implications of loss of microbial diversity as a consequence of modernization? Detailed
dietary analysis in combination with DNA sequencing
of stool samples has its advantages. These techniques
have allowed researchers to determine that long-term
dietary patterns largely determine the main phyla ofthe gut microbial profile [118]. However, psychologicalstress or short-term dietary changes are capable of inducing species-level changes to the intestinal microbiota[119]. While the administration of singular or small
groups of select beneficial microbes may not have amajor impact on stable phyla, probiotic intervention
studies (as discussed previously) have taught us thatspecies-level application of microbes are not withoutclinical relevance. A single strain of Lactobacillus, onethat might be carried with traditional foods, may improveoverall microbial diversity [120]. The administration of asingle Bifidobacterium strain, one among a genera commonly found in fermented dairy products, can increase theintestinal quantity of completely separate Bifidobacterium
species, and Lactobacilli overall [121,122].

The potential of fermented foods
Thus far, we have highlighted that depression and othermental health disorders are characterized by chronic,
low-grade inflammation and oxidative stress. Conversely,a traditional diet rich in antioxidant, anti-inflammatory
foods may confer some level of protection against depression. We have also noted that an intestinal ‘inflammatory
microbiome’ appears to exist, one that may contribute toaltered mood via intestinal permeability, systemic LPS
burden, and even direct-to-brain microbe communication.
Such an inflammatory microbiome may be facilitated, atleast in part, by Western dietary habits. Research showsthat high-fat or high-sugar and low nutrient-value foods arecommonly consumed by those with depression, anxiety,and high levels of chronic distress [123-125], thus contributing to the likelihood of an inflammatory microbiome.
Preliminary research in rodents and human beings suggeststhat the behavioral consequences of an inflammatory
microbiome can be offset by the administration of beneficial
microbes. All this leads us full circle to the ancient Neolithic
vessels in asking to what extent fermented foods or beverages might contribute to mental health. We are certainly
not the first to ask this question in the broad sense; in 1938,
Lloyd Arnold, MD, aptly a professor of both preventive
medicine and bacteriology at the University of Illinois, pondered to what extent ancient diets, fermented foods, andtheir effect on the ‘bacterial flora of the intra-intestinal contents’ converged to promote health [126].
Today, scientific advances allow for some answers in
the direction toward the potential of fermented foods. It

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is well established that with traditional dietary patterns,
fermentation can magnify protein quality [127] and thebioavailabity of mood-regulating B vitamins, magnesium,and zinc [128-131]. The effect of diet on intestinal
microbiota may also extend to vitamin D levels [132].
However, it is also becoming clear that the Lactobacillus
species isolated from traditional fermented foods arebiologically active in other ways, for example, upon oral
consumption, Lactobacillus plantarum strains isolated
from traditional Chinese fermented foods provide strong
antioxidant protection in animals [133]. Fermentation offruit and herbal smoothies with Lactobacillus plantarum
and other strains has been shown to preserve their polyphenolic compounds and vitamin C, and as expected, thisenhances subsequent free radical scavenging activity thatwould otherwise be lost with storage [134]. Fermented
soymilk also has a more pronounced antioxidant capacity
than unfermented soymilk, and this activity is further
enhanced by the synergistic application of both lactic
acid bacteria and bifidobacteria together versus only
Lactobacilli or Bifidobacterium strains alone [135].
The fermentation of fiber-rich components of traditional diets, such as, soy germ, wheat germ, rice bran,or breads made via traditional fermentation techniques,
have been shown to produce novel bioactive compounds
capable of producing beneficial immune, glycemic, andanti-inflammatory activities [136-139]. In the case offermented rice bran, where enhanced phenolic availability has been noted, there is specific experimental
evidence indicating beneficial mental properties via thebioactive compounds. More specifically, compared with
controls, oral administration of fermented rice bran extract reduced experimental fatigue and stress [140,141].
Fermentation of rice bran, and other traditional foods,
such as mung beans, buckwheat sprouts, and lentils, isknown to increase the available GABA content significantly [142-144]. Whereas synthetic GABA in oral form
has been classically dismissed as of limited benefit due
to absorption issues, research has reported value of theoral administration of GABA derived from Lactobacillus
hilgardii fermentation in anxiety reduction in humanbeings, and antidepressant activity via the administrationof GABA-rich red yeast rice [145,146].
Recent evidence suggests that the health-promoting
target of flavonoids is directed toward the human gut
bacterial metagenomes, and that these benefits have an
evolutionary origin. Functional analysis using clusters oforthologous groups of bacteria target proteins suggeststhat flavonoids regulate the metabolism of gut microbiota[147]. Experimental research has shown that when common dietary polyphenols are subjected to fermentation,
the newly formed biotransformation phytochemicals are
more capable of causing a beneficial shift in microbial
growth stimulation [148]. In positioning fermented foods

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as worthy of discussion for cognitive and mental benefits,
recent comparative research involving fermented andnon-fermented foods and herbal ingredients is worthy of
consideration. Researchers have examined the in vivo
properties of an herbal blend typically used in traditional
medicine to treat inflammatory disorders, comparing
its effects in the unfermented and fermented form. Blood
LPS levels were significantly lower when treated with thefermented blend, as was C-reactive protein, a primarymarker of systemic inflammation. There was also a significant reduction in LPS-induced intestinal permeability anda significant rise in stool Lactobacillus species, neither ofwhich was noted with the unfermented blend [149].
Similar research has been documented with fermented
and unfermented herbs used for gastrointestinal disorders,that is, more pronounced anti-inflammatory activity andminimization of LPS-induced gene expression with the fermented blend [150]. In separate work involving a singular
traditional food or medicinal agent, the anti-inflammatory
botanical Sophora flavescens, researchers, again using LPS
as the inducing agent, found a more pronounced antiinflammatory and antioxidant activity with the fermented
form [151]. Recently red wine has been shown to increase
Bifidobacterium levels, which in turn correlates with lower
serum LPS concentrations [152]. Fermented grape pomace
yields more total antioxidants and antioxidant activity thanits unfermented counterpart [153]. Remarkably, evenfermented fish oil, an agent with well-documented antiinflammatory and mood-support properties, has beenshown to provide an enhanced anti-inflammatory activity
versus its unfermented counterpart [154]. Given our previous discussions concerning LPS-induced inflammation, intestinal permeability and glycemic control, it should not be
surprising, perhaps, that fermented (versus unfermented)
dairy products can improve glucose metabolism and improve antioxidant status in human beings [155,156].
The connection between fermented dairy products andthe growth of beneficial intestinal microbes has been welldescribed. However, the findings that (non-dairy) fermented foods and herbs can have a positive influence on theintestinal microbiota are important in that there may be an
influence on longer-term gut-brain communication. For example, isomalto-oligosaccharides are found in traditional
foods (for example, honey, sake, miso, and soy sauce) andhave been shown in animals and human beings to have abeneficial effect in promoting the growth of Bifidobacteria
and Lactobacilli [157]. Providing just a few examples, fermented (versus unfermented) burdock has been shown tosignificantly promote the growth of bifidobacteria [158];
similar findings have been reported for fermented versus
unfermented soy [159]. The species-level microbiota within
local fermented foods is reflected in stool samples of thehuman host [160]. When researchers make discoveries suchas that showing that a Lactobacillus pentosus strain derived

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from fermented cabbage (kimchi) can improve mental
functioning and hippocampal BDNF production in animals[161], the entire mosaic takes on greater meaning. It suggests that we are only scratching the surface in our understanding of the relationship between potentially beneficial
food-derived microbes and brain health.

Conclusions
The purposeful application of fermentation for foodpreservation, palatability, and other reasons is an ancientart. Modern research is highlighting the potential valueof ancestral dietary practices on mental health, and on
resiliency against depression in particular. At the sametime, there has been tremendous progress toward better
understanding of the role played by the low-grade inflammation and the intestinal microbiome in human health andmental well-being [162,163]. Evidence would suggest thatthe two major themes of these mostly separate highways of
research should converge; in other words, the fermented
foods so often included in traditional dietary practices havethe potential to influence brain health by virtue of the
microbial action that has been applied to the food orbeverage, and by the ways in which the fermented foodor beverage directly influences our own microbiota. This
could manifest, behaviorally, via magnified antioxidant
and anti-inflammatory activity, reduction of intestinal
permeability and the detrimental effects of LPS, improved glycemic control, positive influence on nutritional
status (and therefore neurotransmission and neuropeptide
production), direct production of GABA, and otherbioactive chemicals, as well as a direct role in gut-tobrain communication via a beneficial shift in the intestinal
microbiota itself.
In this discussion, we may unwittingly give the impression that fermentation is exclusively a beneficial application to food and beverage production. Such is not thecase and not all forms of fermentation or fermented foods
can be painted with the same brush. For example, certain
microorganisms (for example, fungi) associated withpickled foods may enhance the production of N-nitroso
compounds with potential carcinogenic properties [164].
Also, although agmatine and other polyamines found infermented meats, fish, and certain beverages have beenshown to have a variety of experimental benefits related
to brain health [165,166], a safe level of intake remains
unknown [165]. However, as outlined in our review,
there is more than ample justification to follow the
microbe-nutrition and gut-brain research pathways into
convergence. The clinical world of mental health involves
one where consumption of convenient, high-fat, or
high-sugar foods is the norm; these foods, at odds with
our evolutionary past, are not only undermining optimal
nutritional status, they have untold effects on the microbiome and ultimately the brain. Hopefully, further researchSelhub et al. Journal of Physiological Anthropology 2014, 33:2
http://www.jphysiolanthropol.com/content/33/1/2

will continue to illuminate the ways in which the clay fermentation pots of our ancestors might be connected to theemerging discipline of nutritional psychiatry.
Abbreviations
BDNF: brain-derived neurotrophic factor; fMRI: functional magnetic
resonance imaging; GABA: gamma-aminobutyric acid;
LPS: lipopolysaccharide endotoxin.
Competing interests
ACL has received consulting fees from Genuine Health, Toronto, Canada.
EMS and ACB have no competing interests.
Authors’ contributions
All authors contributed equal time and effort to the investigation, research,and drafting of this manuscript. All authors read and approved the final
manuscript.
Author details
1
Harvard Medical School and Massachusetts General Hospital, 40 Crescent St.,
Suite 201, Waltham, MA 02453, USA. 2CAMNR, 23679 Calabasas Road Suite
542, Calabasas, CA 91302, USA. 3Complex Chronic Diseases Program, BC
Women’s Hospital and Health Centre, B223A-4500 Oak Street, Vancouver, BC
V6H 3N1, Canada.
Received: 11 July 2013 Accepted: 18 December 2013
Published: 15 January 2014
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doi:10.1186/1880-6805-33-2
Cite this article as: Selhub et al.: Fermented foods, microbiota, andmental health: ancient practice meets nutritional psychiatry. Journal of
Physiological Anthropology 2014 33:2.

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