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Journal of Pharmacology & Clinical Toxicology
Cite this article: Thakur AK, Shakya A, Husain GM, Emerald M, Kumar V (2014) Gut-Microbiota and Mental Health: Current and Future Perspectives. J
Pharmacol Clin Toxicol 2(1):1016.
*Corresponding author
Vikas Kumar, Neuropharmacology Research
Laboratory, Department of Pharmaceutical
Engineering, Indian Institute of Technology (Banaras
Hindu University), India, Tel: +91-542-6702742; Fax: +91-
542-2368428; E-mail: vikas.phe@iitbhu.ac.in
Submitted: 22 November 2013
Accepted: 02 January 2014
Published: 12 January 2014
Copyright
© 2014 Kumar et al.
OPEN ACCESS
Keywords
•Gut-microbiota
•Probiotics
•CNS
•Gut- brain axis
Review Article
Gut-Microbiota and Mental
Health: Current and Future
Perspectives
Ajit Kumar Thakur
1
, Anshul Shakya
2
, Gulam Mohammed
Husain
3
, Mila Emerald
4
and Vikas Kumar
1
*
1
Neuropharmacology Research Laboratory, Department of Pharmaceutical
Engineering, Indian Institute of Technology (Banaras Hindu University), India
2
Department of Pharmaceutical Sciences, Dibrugarh University, India
3
Central Research Institute of Unani Medicine, India
4
ATL International & Phytoceuticals International, Canada
Abstract
Recently, there is a growing interest of research on the relationship of gut-micro-
biota and neurological disorders. Increasing number of ndings suggests the broader
role of gut-microbiota in the modulation of various physiological and pathological con-
ditions and it is now well recognized that a bidirectional communication between brain
and gut-microbiota is essential to maintain homeostasis. The gut-brain axis includes
central nervous system (CNS), the neuroendocrine and neuroimmune systems, autonomic
nervous system, enteric nervous system, and intestinal microbiota. Probiotics (i.e., live
microorganisms similar to benecial microorganisms found in the human gut) are re-
ported to modulate a number of disorders including metabolic disorders, behavioral
conditions and cognitive functions. This review covers the signicance of gut-brain axis
in relation to the overall mental well-being. Apart from the recent studies highlighting
the importance of gut-brain axis, here we also reviewed the interaction of few herbal
medicines with gut-brain axis. Animal studies have indicated that some herbs or their
isolated constituents alter the normal gut ora and have prominent effect on behavior-
al condition such as anxiety depression and cognition. Thus alteration of gut-brain axis
by traditional medicines will be a potential strategy for the management of comorbid
CNS disorders and gastrointestinal problems.
INTRODUCTION
The concept of the gut-brain axis, a term which describes
the complex bidirectional communication system that exists
between the central nervous system and the gastrointestinal tract
and which is vital for maintaining homeostasis [1,2]. The gut-
brain axis is involved in a multitude of physiological processes
including satiety, food intake, regulation of glucose and fat
metabolism, insulin secretion and sensitivity, bone metabolism
[3,4], and lifespan [5].
Emotional or physical stressors may cause disturbances at
every levels of the brain-gut axis including the central, autonomic
and enteric nervous systems and affect regulation of visceral
perception and emotional response to visceral events [6]. Brain
communicates with the gut through multiple parallel pathways
including autonomic nervous system, the hypothalamic pituitary-
adrenal axis, and other connections, which were termed the
brain-gut axis [7,8]. Based on previous studies there is strong
evidence that exposure to stress, and release of catecholamines
and norepinephrine into the GI tract during stress [9], may be
responsible for the dysregulation of the gut-brain axis, via
changing the GI motility, secretion of mucus and epithelial cells,
thus leading to the different diseases of the gut [10]. It is also
found that stress doing the early maturity life in animal, produces
increased levels of corticosterone [11]. Epidemiological studies
have implicated stress of psychosocial, physical or immune
bowel syndrome symptoms [12-14]. In adult irritable bowel
syndrome patients, acute stress episodes, chronic social stress,
anxiety disorders, and maladaptive coping style determine
the illness experience, health care-seeking behavior as well as
treatment outcome [15,16]. Stress-related psychosocial factors
such as somatization, neuroticism, and hypochondriasis are
also important predictors in the development of post-infectious
irritable bowel syndrome [17,18]. Microbiota provides the
[19]. It has been shown that microbiota helps and protects
the host against the viruses indirectly via activation of the
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[20,21]. Interestingly, in spite of the fact that microbiota help the
by stimulating the proliferation or activation of target cells [22].
There is a growing appreciation of the critical role played by
the commensally microbiota, both in our general wellbeing and
bacteria may respond directly to stress-related host signals
because of interplay between stress and gut microbiota. Thereby,
in many hosts [23].
Microbiota and host-metabolism
The human gastrointestinal microbiota represents a
complex ecosystem that consists of bacteria, archaea, yeasts,
Senegal virus [24-30]. The human gastrointestinal tract typically
comprises more than 10 times microbial cells that of the number
of human cells in our bodies and contain ing 150 times as many
genes as our genome [31,32]. The gut microbiota is therefore
often referred to as the forgotten organ. The estimated number
of species in the gut microbiota varies greatly, but it is generally
accepted that the adult microbiota consists of more than 1,000
species which are belong to a few bacterial phyla [33], and more
than 7,000 strains [32,34,35]. Interestingly, the gut microbiota
modulated the expression of genes involved in immunity,
nutrient absorption, energy metabolism and intestinal barrier
function in human or mouse intestine [15].
relationships, which assure balanced habitat [36]. The
compositions of the microbiota play an important role in the
maintenance of intestinal homeostasis and host health [37].
Through the cooperative action of different functional microbial
groups, the gut microbiota synthesizes essential amino acids and
vitamins. In addition, by deploying an array of glycosidehydrolases
and polysaccharide lysases, the microbiota facilitates utilization
of otherwise indigestible food compounds [34,38]. Fermentation
of saccharides by gut microbiota is the main source of energy
for intestinal epithelial cells [26]. Microbial de-polymerization
of complex carbohydrates and proteins gives rise to mono- and
oligomeric compounds that are subsequently fermented into
of calcium, magnesium, and phosphorus [40].
For more than 50 years we have known that the administration
of low doses of antibacterial agents promotes the growth of farm
animals, consequently, in the United States, the largest use of
antibiotics and related antimicrobial substances is within farms,
with low doses fed to large numbers of animals used for food
production to increase weight gain [41]. There are two main
mechanisms by which it can maximize nutrient availability,
either by the release of calories from otherwise unavailable
gut microbiota can cause number of diseases for example, it has
been shown that an increased ratio of the phylum Firmicutes to
the genus Bacteroides is linked to obesity [43].
in supporting host digestion and metabolism, obesity has been
considered as an illness with a potential microbial basis [44].
Till 2004, there is over 138 data publications and 60 reviews for
not be considered in isolation because obesity is a multifactorial
condition that also involves strong genetic factors, hypothalamic
dysfunction, and an increase in the consumption of energy-dense
produced by the gut bacteria, and Gpr41 increases circulating
levels of PYY, an enteroendocrine hormone that reduces gut
representation of Microbiota host metabolism is depicted in
Figure 1.
Several nutrients, including L-glutamine, L-glutamate,
glucose, and sucrose, have physiological effects such as
protecting the gastric mucosa, improving emotional state, and
supplying energy in the subconscious state. These nutrients can
also modulate subsequent behavior, such as brain activation and
behavioral modulation resulting from internal signaling through
the gut-brain axis [49]. Ingested nutrients are digested and
absorbed in the gastrointestinal tract. The afferent vagus nerve,
which innervates the entire gastrointestinal tract and projects to
the nucleus of the solitary tract, is then activated, or peripheral
humoral factors such as insulin and glucagon like peptide-1
recent studies have indicated that the stomach, duodenum, and
intestine contain chemosensing taste receptors and some kind
which is related to the chemoreception of the sweet and the
chemoreception of the bitter taste, are both expressed in the
and the gastroinestinal tract in rodents. Fatty acids interact
brain regions, including the amygdala and the periaqueductal
gray matter [55-57]. Intragastric infusion of glucose solution
increases blood glucose, GLP-1, and insulin, and circulating GLP-
the intragastric administration of glucose correlate with the
blood oxygenation level-dependent response in the amygdala,
ventromedial hypothalamus, and nucleus accumbens [49,58].
The GI tract also is a locus of hormone production, including
a model of obesity by treating mice at their early life time by
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level of various antibiotics in their drinking water, and reported
mineral density and GIP level. The increase GIP level was in
alterations of the microbiome may affect pluripotent cells that
can become osteoblasts, adipocytes, or myocytes. Postulated
metabolic activity that were able to extract a higher proportion
of calories from dietary complex carbohydrates that were
concentrations are the metabolic products of this activity, which
then may be delivered in increased quantities through the portal
circulation to the liver, enabling enhanced lipogenesis. Enhanced
caloric absorption has been implicated as a mechanism for
increased weight gain in other murine obesity models [41].
Microbiota-gut-brain axis
In general the brain–gut–enteric microbiota axis includes
sympathetic and parasympathetic arms of the autonomic
of course the intestinal microbiota. During the feeding, the gut
released peptides which are affecting hypothalamic pathways,
and especially arcuate nucleus involved in the regulation of
satiety and metabolism. Put simply, through this bidirectional
motor, sensory, and secretory modalities of the GIT and conversely,
The vagus nerve is the direct communication observed between
bidirectional communication represented in Figure 2. The cross
talk between gut microbiota, the immune system and the brain-
gut axis plays an important role in the modulation of the stress
response of the gut in the context of the development of different
gut disorders as microbiota communicate with the gut-brain
axis through different mechanisms viz. direct interaction with
[2].
Microbiota also interacts with host gut-brain axis through
and behavior [62]. For example, alteration in gastrointestinal
function is communicated to the brain bringing about the
perception of visceral events such as nausea, satiety, and pain or
when, in turn, stressful experiences lead to altered gastrointestinal
secretions and motility [63]. The neuroendocrine, neuroimmune,
the sympathetic and parasympathetic arms of the autonomic
nervous system and the enteric nervous system are the key
pathways through which they communicate with each other [64].
conditions and other disorders [65]. Putative mechanisms by
microbial products that gain access to the brain, via cytokine
release from the mucosal immune cells, via the release of gut
hormones such as 5-HT from endocrine cells, or via afferent
neural pathways, including the vagus nerve. Stress and emotions
the release of stress hormones or sympathetic neurotransmitters
alter the habitat of the microbiota and also these catecholamine
alter the growth, motility and virulence of pathogenic and
signaling between bacteria, and this might change the microbial
composition and activity of the microbiota [66].
Figure 1
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Some of the earliest indications of a critical role of the gut
microbiota in stress responses are well recognized. Germ-free
This hyper responsiveness was reversed by reconstitution with
feces from animals kept in a pathogen- free environment or
with a single bacterial strain, [67]. More
recently, two studies have indicated that germ-free conditions
during early growth of mice results in decreased anxiety-like
neural correlates of reduced anxiety in germ-free animals, Diaz et
lower in various sub-regions of the prefrontal cortex, including
the orbital frontal cortex and the striatum, hippocampus dentate
cortex, which are important components of the neural circuitry
underlying anxiety and fear [70, 71]. In addition to altered
Enhanced turnover rate of noradrenaline, dopamine, and 5-HT
has also been demonstrated in the striatum of germ-free mice
Gut microbiota and neurotransmission
se of some of the major
brain neurotransmitters which act in the gut-brain axis and
modulate food intake and energy balance [72] i.e., short chain
endocannabinoid ligands, cholecystokinin, and ghrelin. The gut
hormones affect glucose metabolism by altering food intake,
body weight, insulin sensitivity, gastric delay, gut motility,
glucose levels and plasma glucose levels. It has been shown that
low doses of PYY3-36 and GLP-1 can additively reduce food
produced by the gut bacteria, and Gpr41 increases circulating
germ-free mice present with a 2.8-fold increase in plasma
of 35624 to Sprague-Dawley rats,
for example, has been shown to induce an elevation in plasma
tryptophan levels, a precursor to serotonin [75].
Serotonergic neurotransmission modulates many brain
functions including emotion, cognition, motor function, pain as
well as neuroendocrine functions such as food intake, circadian
rhythms and reproductive activity [76]. 5-HT is an important
signaling molecule in the brain-gut axis and the 5-HT released
compulsive behavior was observed in irritable bowel syndrome
and state anxiety and simulation/social ingenuity was found in
these patients. In diarrhea-predominant IBS, plasma cortisol was
linearly related to plasma serotonin [78].
Figure 2
disorders and dysbiosis. Similarly dysbiosis effect synthesis of several microbial by-product and precursor that gain access to the brain via the bloodstream and the area
afferent neural pathways, including the enteric nervous system.
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with alterations in the expression or content of various gut
hormones linked to the regulation of energy balance, notably
increasing the satiety hormone PYY and reducing the expression
of the orexigenic peptide ghrelin [79]. It has been demonstrated
that prebiotic treatment was increasing plasma levels of GLP-1
and PYY [80]. Probiotics are capable of producing and delivering
neuroactive substances such as gamma-aminobutyric acid and
serotonin, which act on the brain-gut axis. Preclinical evaluation
of probiotics in rodents suggests that certain probiotics possess
antidepressant or anxiolytic activity and therefore, better called
as psychobiotics [81].
of life and affects the brain’s normal development of social and
communication skills [82]. Interestingly in a study of 58 autism
patients >90% had gastrointestinal problems compared to none
in the control group [83]. There is evidence to support alterations
of the fecal microbiota in patients with autism, with an increase
the pathogenesis of GI disturbances in children with autism [86].
Metagenomic analyses demonstrate a dysbiosis with reductions
in Bacteroidetes and increase in the ratio of Firmicutes to
Bacteroidetes, as well as in Betaproteobacteria [87]. In case of
antibiotic that targets gram positive anaerobes and is minimally
absorbed by the GIT, can improve symptoms [88]. The possibility
of microbiota involvement in development of Parkinson disease
and cerebrum metabolic changes has been discussed [89]. It has
been shown that increased peptidoglycan production by the gut
metagenome may contribute to symptomatic atherosclerosis.
Because atherosclerosis is associated with lipid accumulation
treated mice [92,93], as well as fat deposition in the liver [94,95].
There is also a number of publications on the potential role of
microbiota’s misbalance in case of perinatal programmed asthma
Bercik et al. reported that alteration in the brain-derived
hippocampus and amygdala in mice of antibiotic-induced
dysbiosis [99]. Oral administration of non-absorbable
antimicrobials to SPF mice transiently altered the composition
of the microbiota and increased exploratory behavior and
treated mice were greatly higher in the hippocampus and lower
have also been implicated in the pathogenesis and treatment of
and its mediated signaling may participate in the pathophysiology
been reported in animal models of depression [101] and it is
common substrate through which alteration in the gut microbiota
mediate the behavioral effect.
Gut-mirobiota and immune system
Series of studies summarized in recently published reviews
indicate a critical role of intestinal commensally microbiota in the
bowel diseases, rheumatoid arthritis and multiple sclerosis
[103,104]. The vertebrate GI tract contains an exceptionally
complex and dense microbial environment, with bacterial
constituents that affect the immune responses of populations of
reactive host cells [105], and stimulate a rich matrix of effector
mechanisms involved in innate and adaptive immune responses
[32].
More recent studies substantiate these assertions with
proliferation thus accelerating repair of the epithelial surface
vitally important not only for protection from pathogenic infection,
but also for inducing tolerant responses to commensalism. The
intestinal epithelial integrity through translocation of the
The basic mechanism of the mucosal immune system is innate
immunity and its characteristic ability to distinguish potentially
pathogenic microbes from harmless antigens is achieved through
innate immune system and recognize characteristic molecules
called pathogen associated molecular patterns [109]. Pathogen
resulting in increased cytokine production and T cell activation
of studies which found a persistent elevation in rectal mucosal
enteroendocrine cells, T-lymphocytes and gut permeability
following the infectious insult in subjects who went on to develop
bacteria, improve the barrier effect of the GI mucosa and more
immune system [113]. Multiple studies are regarded as important
indicators of a link between alterations in the microbiota and
both during and after the infection, compared with individuals
who do not develop PI-IBS [117]. IBS patients with normal
cells in IBS suggests an antigen challenge and these cells are
It has been hypothesized that changing diets are altering
the gut microbiota towards dysbiosis and may thus be driving
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factors apparently associated with dysbiosis in animal models
diets are associated with lower levels of short-chain fatty acids
are associated with rheumatoid arthritis [120]. Increased
to other tissues occurs in obese murine models as a response to
fat feeding [121], and enhanced systemic exposure to LPS could
ratio of fat to muscle mass, so-called sarcopaenic obesity [122],
but debate continues about whether sarcopaenia is a cause or an
effect of rheumatoid arthritis.
Microbial infections were thought to trigger multiple
evidence, which suggests that commensal bacteria contribute to
MS pathogenesis, the effects of diet on MS development provide
induced in experimental animals via immunization with myelin
antigens in combination with a strong adjuvant. In contrast,
sterilization of the gut by treatment with a mixture of antibiotics
demyelinating disease is thought to be due to the attenuation
H
1/T
H
17 responses. Lee and colleagues
showed that disease protection in germ free mice coincided with
and increased numbers of Forkhead box P3
Moreover, IL-10-producing, Foxp3
Stress and gut microbiota
The core neuroendocrine pathway in human is the
this axis takes place in response to a variety of physical and
elegant study by Sudo et al. provided some insight into the role of
Signaling molecules released into the gut lumen from cells
result in changes in gastrointestinal motility and secretion as
well as intestinal permeability, thus altering the GIT environment
in which the bacteria reside [2].
Stress affects our Brain and GI tract both ways:
hypothalamic-pituatary-adrenal pathway and the autonomic
nervous
and noradrenaline secretion, and corticotropin-releasing-factor
permeability within the lining of the bowel.
in a kind of sensory hyperactivity.
Stress also induces permeability of the gut allowing bacteria
and bacterial antigens to cross the epithelial barrier and this can
activate a mucosal immune response which in turn alters the
to cause an increase in colonic paracellular permeability which
on stress related pathology in upper GI tract, however the effects
need to be further evaluated [133]. There is also evidence that
to increased adhesion and translocation of bacteria due to
intestinal barrier, making it leaky and increasing the circulating
levels of immune modulator bacterial cell wall components
such as lipopolysaccharide [134]. Stress may be an important
factor leading to the activation of the immune system resulting
in the exacerbation or induction of acute colitis [135,136]. The
modulator role of stress-related brain-gut interactions in the
IBS pathophysiology, in particular neuroimmune modulation
associated with psychological factors and emotional state
non-pharmacologic and pharmacologic treatment modalities
developments showing the critical interdependence between the
composition and stability of the microbiota and GI sensory-motor
function indicate a novel approach to IBS treatment with a use of
of the enteric microbiota in the context of neuroimmune
interactions within the brain-gut axis opens a new promising
strategy for stress-related disorders, particularly in the aspects
of comorbidity in functional GI disorders such as IBS [1,142].
neonatal animals leading to features of depression and anxiety
that persist into adulthood [143].
reported a very high lifetime prevalence of generalized anxiety
disorder of 34% in newly referred IBS patients [144]. Talley et al.
reported that dyspepsia patients who present for investigation
were more likely to be neurotic, anxious, and depressed
than non-dyspepsia controls [145]. Using the gold standard
diagnostic method with psychiatrist-conducted structured
are diagnosed in 38% of patients with functional dyspepsia
compared with 4% in the general population [146]. It has been
shown that stress or bacterial-mediated disruption of epithelial
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tuning-down mechanisms may lead to longstanding increase of
gut permeability and hypersensitivity [147].
It has also been observed that IBS patients with psychiatric
morbidity are characterized by low rectal distension pain
thresholds, high rates of healthcare consultations, interpersonal
problems and sexual abuse [148]. In a population based study
likelihood of having generalized anxiety disorder [149]. Yet, there
are cumulating evidence showing that the pathophysiology of
processing of visceral nociceptive signals in the brain-gut
axis, which leads to visceral hypersensitivity and hyperalgesia
[150]. Furthermore, FGID patients are also characterized by
abnormalities in autonomic, neuroendocrine and immune
functions. This neural network involves corticotrophin releasing
the autonomic nervous system and hypothalamus-pituitary-
related, which includes anxiety, depression, and changes in
gastrointestinal motility and visceral sensation [147].
The system is involved in a wide spectrum of physiological
activities such as arousal, vigilance and pain modulation.
Hyperactivity of the neuroendocrine and visceral perceptual
visceral hyperalgesia and negative affective response to bowel
symptoms of hard or lumpy stools in constipation- predominant
IBS [153,154]. It has also been reported that anxiety induces
gastric sensorimotor dysfunction and postprandial symptoms in
patients with functional dyspepsia [155]. Psychological disorders
and FGID also share common genetic predispositions particularly
the genes that are involved in serotonergic activities. It has been
reported that the polymorphism of serotonin reuptake transporter
response to serotonergic medications in depression as well as
colonic transit response to alosetron, a serotonin receptor-3
[157]. Early life adversity, particularly psychological stress, has
been speculated to play an important role of pathogenesis of
FGID. Other social and environmental factors, such as exposure
to war time conditions, infantile and childhood trauma and
social learning of illness behavior are predictors of the IBS in
adulthood [158,159]. In recent years, a positive association
between psychological stress and abnormal immunity has also
been implicated in the pathophysiological mechanism of IBS.
IBS patients have coexisting hyperactivity of the hypothalamic-
increase in mucosal permeability and decrease in secretory
response of intestinal epithelium to luminal stimuli [160]. It has
been shown that the change in intestinal mucosal permeability is
attracted attention as a disorder with an aberrant GIT microbial
increase in the Proteobacteria classes of bacteria evident [168].
Furthermore, in terms of exogenous microbial threats, the
frequency of has been shown to be higher
in IBD and may trigger relapse where the disease is established
but in remission [169]. It is well recognized that psychological
stress, a factor which can perturb the microbiota, exacerbates
support a role for the microbiota in the pathophysiology of IBS
and chief among these is the supporting data for PI-IBS, a term
which describes the development of IBS following an episode of
Microbiota-gut-brain axis and role of probiotics
The idea of connection between gut-microbiota and onset of
mental illness based on ‘autointoxication’ and ‘intestinal toxemia’
theory and toxemia were used to describe a process where
microbiologist Ilya Metchnikoff added great explanation for
mental health disorders, which development could be connected
of behavioral and mood disorders, and psychosis as well [175]. In
as
a potential treatment for different health conditions, because “...
acidophilus, the twin brother of , is much more
Elie Metchnikoff, that orally consumed lactic acid bacteria could
combat the dangers of autointoxication, could slow the aging
via to slowing arteriosclerosis and improve the quality of life
[179], Frederick Forchheimer [180] and was carried out through
the early 1930s. In 1945 Danish scientists found that older adults
with dementia had the highest level of clostridia species [181].
of mental illness was proposed by Scottish physician Hubert
properly powered studies are required before using probiotics in
treatment of depression [183].
behavior and brain chemistry is well documented [67,184]. It
which activated calcium dependent potassium channels in
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enteric neurons in the colonic myenteric plexus, proves that that
gut microbiota may affect brain via autonomic nervous system
the microbiota in maintaining normal brain function offers the
intriguing possibility that the therapeutic targeting of the gut
chronic fatigue syndrome, which is a result of prolong IBS which
is characterized by neuropsychological and cognitive problems,
as well memory loss, lack of concentration, bad sleep, moodiness,
anxiety and depression [188, 189]. The results of a recent study
human volunteers following administration of a combination of
[190]. 35624 treatment, for example,
was shown to normalize immune responses, reverse behavioral
concentrations in the brainstem of adult rats subjected to the
early life stress of maternal separation, an animal model of brain–
gut axis dysfunction [60,191].
hypersensitivity in a mouse preclinical model of IBS [192].
Furthermore, a preclinical study using the same probiotic found
[165,193]. These reports raise the possibility that therapeutic
targeting of the microbiome might be an effective treatment
supporting gut health through microbiota supplementation with
putative preventative strategy worth following [194]. In addition
to consideration of the microbiome as a therapeutic target, we
also need to direct more efforts toward mining its metabolites for
putative drugs, a strategy that has already paid some dividends
[195].
The probiotic
produces an anxiolytic effect in two different models of
anxiety-like behavior as assessed by light/dark preference and
step-down tests [184,196,197]. Evidence that microbiota are
linked to brain chemistry and behavior is well documented, an
interestingly abnormal behavior was displayed before there
indicating that this behavior was not a consequence of cytokine-
induced reactions, but a interaction between the gut microbiota
and the neural system. Infestation of mouse with H. pylori
infection has been shown to lead to change in behavioral pattern
and changes in neural biochemistry accompanied with following
dyspepsia [198]. Using of probiotics, for example administration
of to DSS-treated mice reversed their
effect of on enhancement of exploratory
behavior [184]
In contrast, the effect of
and elevated plus maze tests vs. an anxiogenic effect reported in
stress-induced hyperthermia [61,199].
Gut-micobiota and ayurvedic biology
It is now well recognized, that most polyphenolics consumed
with meals are extensively metabolized in the gastrointestinal
tract. Phloroglucinol is a polyphenolic phytoconstituent,
2
[200,201], and is also known to possess antibacterial activities
[202]. Thus it can alter the gut microbiota ecology, which is
well recognized to be an integral part of human physiology
produced anxiolytic effect which was absent in intraperitoneal
administered animal [205]. The gut microbiota ecology and the
gut brain axis play important roles in altering central sensitivity
antifungal, and antiparasitic activities of
triggered thermoregulatory mechanisms observed due to its
effects on gut microbiota ecology [206,207].
deteriorated brain functions and cognitive performance in
diabetic rats [208]. Dietary manipulation is an emerging strategy
reported that administration of probiotic
reduced insulin resistance as well as hepatic steatosis formation
[210].
such as anxiety and depression. Several reports including studies
in anxiety, depression and stress related conditions
are available regarding antibacterial activity of crude plant
extracts of [219,220]. Hyperforin, the
major bioactive constituent of , inhibited
the growth of gram-positive bacteria such as
strains were also susceptible to
hyperforin [221]. Therefore, alteration of gut microbiota by oral
administration of extract may be partly
Studies in germ-free animals are required to clarify the role of
and its isolated bioactive constituents
such as hyperforin in stress and related conditions.
Since last many years we have been working on holistic
psychopharmacological approach to discover effective natural
remedies for neurological disorders probably working through
gut-microbiota theory [206,212-218,222-231].
Current and future perspective
It is now established that there is symbiotic interaction
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between gut-microbiota and mental wellbeing and the integrity
of both of these factors is essential to maintain the homeostasis.
and behavioral changes in animals as well as in clinical studies.
Modulation of the gut-microbiota by therapeutic agents opens a
new promising strategy for stress-related disorders, particularly
in the aspects of functional GI disorders such as IBS. Probiotics
have shown promising results in the management of anxiety and
depression and there is a need to further explores the potential of
probiotics as well as prebiotics for the management of metabolic
efforts are required to explore the interaction of herbal medicine
with gut-brain axis. Further, as the use of probiotics is growing
exponentially, there is a need to determine the long-term safety
of such therapeutic intervention.
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