**3. Special experimental models**

Disorders of the gut microbiome have been experimentally documented in some brain diseases and stroke. In animal models of AD, PD, and acute stroke, dysbiosis, intestinal motility disorders, and/or increased intestinal permeability were demonstrated. A pro-inflammatory immune response and increased microglia reactivity were recorded, compared with a non-diseased condition. Special experimental

models of non-microbial or GF animals were used to determine the influence of microbiota on the mechanisms of stroke development [33].

From these gnotobiotic animals, it is possible to decipher mechanisms of communication between specific members of the microbiota and the host organism. Animals lacking microbiota have extraordinarily different development and physiology than animals hosting commensal bacteria. GF animals have impaired immune systems, dysregulated hormone signaling, altered metabolism, and differences in neurotransmission from their conventional counterparts [34, 35].

GF mice show an underdeveloped microglia phenotype, which is manifested by an incomplete immune response to damage. In an experimental stroke model, GF mice showed an incomplete response to brain damage; there was no delineation of the damage locus, which was manifested by an increase in the volume of damage compared to normal animals. Thus it was determined that the microglia of GF animals is morphologically immature [36].

The most common form of dementia is AD, a neurodegenerative disorder associated with impaired cognitive function. This pathology is characterized by extracellular beta-amyloid (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein [37].

When studying the connection of microbiota with the brain, one of the tasks is to find evidence of bacterial participation in AD pathogenesis through the formation of amyloid. The results of an experimental model of AD on transgenic mice revealed a tendency to the expression of amyloid precursor protein-β (APP). When these mice were kept in non-microbial conditions, cerebral β-amyloid plaques were less developed than in a normal environment [38]. This experiment indicates that the microbiota is involved in triggering adverse changes in the brains of transgenic animals, but undoubtedly this depends on the species composition and metabolic activity of the bacteria. For example, in AD participants, the gut microbiome has a reduced microbial diversity and taxonomically differs from the control age and sex correspondences of individuals, in particular, in AD compared to the control the number of *Firmicutes* and *Bifidobacterium* was reduced, but the number of *Bacteroidetes* was increased. The potential amyloidogenic properties of gut bacteria were evaluated and the composition of the microbiota and the aggregation of cerebral amyloid-β were also influenced by nutrients [11, 39, 40].

Several studies have reported that the microbiome of young mice differs significantly from that of older mice, in particular in the ratio of *Firmicutes* to *Bacteroidetes*. The benefits of the microbiota of young mice were demonstrated in an experiment on stroke models, in which transplantation of the gut microbiota from young to old mice contributed to an improvement in the outcome of stroke [41].

There are some limitations in experiments with GF animals because animals with a diverse microbiota have more developed intestinal epithelium than GF animals, which affects the functioning of the body as a whole. Studying the participation of microbiota in the functioning of the brain may be not always correct in case of comparison of the results obtained in GF and normal animals. The new approach avoids these difficulties by using special mice with a modified microbiota, called the altered Schaedler flora (ASF) mouse line, because they are colonized by only eight species of known bacteria [42].

The majority of research showing that microbiota can influence the nervous system has been performed in animals. As such, there is a strong need for well-designed human cohorts. Neuroactive compounds of microbial origin can directly modulate not only neuronal function and plasticity but also human behavior also [5].

**33**

*"Dialogue" between the Human Microbiome and the Brain*

**4. Microbiome and human mental health**

the kynurenine pathway in schizophrenia [44].

but also the severity of depressive disorder [51].

**5. Microbiome and inflammatory events after stroke**

with ASD [46].

results [47].

status, including by studying and correcting the microbiome.

The metabolism of tryptophan via the kynurenine pathway leads to the formation of kynurenine and its neuroactive metabolites, such as 3-hydroxykynurenine, kynurenic acid, quinolic acid, and xanthurenic acid. The involvement of kynurenine and its metabolites in the pathogenesis of depressive disorders and schizophrenia is being studied [43]. For example, in patients with schizophrenia, an increased concentration of 3-hydroxykynurenine in the blood was measured. It is important to note that after targeted treatment, the level of this metabolite was normalized. This fact indirectly confirms the initial violation of tryptophan metabolism along

According to the 2016 report, "The Five Year Forward View for Mental Health," from the independent Mental Health Taskforce to the NHS in England, mental disorders in the modern world affect every fourth person on the planet [45], which is a serious justification for the search for new mechanisms of the influence on mental

A clinical study examined how the gut microbiota and its associated metabolites were changed in sleep disorders in children with autism spectrum disorders (ASD). There was a decrease in the abundance of *Faecalibacterium* and *Agatobacterium*, a decrease in 3-hydroxybutyric acid and melatonin, and an increase in serotonin levels. These changes can worsen sleep problems and major symptoms in children

Some studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms; others have demonstrated potential benefits of probiotics in correcting dysbiosis and reducing the severity of ASD symptoms. The general conclusion of these studies is that future research based on more randomized controlled studies with larger population sizes and standardized use of strains, concentration of probiotics, duration of treatments, and methods of DNA extraction is needed in this area, which may lead to more robust

According to the World Health Organization, mental disorders are quite common even in people who lead a seemingly normal lifestyle [48]. At the same time, new evidence suggests that less than 10 percent of mental and neurodegenerative diseases have a strict genetic etiology. Other predisposing and concomitant factors, such as stress, environmental exposures to potentially toxic elements, and other factors may influence neurometabolism, which may increase the risk for depression, autism, sclerosis, PD, and AD [49, 50]. Among these factors, an important place is occupied by the gut–brain microbiome relationship at the level of metabolomic connections, which allow us to conceptually rethink the causes and mechanisms of mental health disorders. Possibly in some categories of people with predisposition, the metabolic activity of the gut microbiome may affect not only the development,

The gut inflammatory and immune response can play a key role in the pathophysiology of severe course and development of complications after stroke. This can be judged by studying the mechanisms that occur in the brain when damaged. Proinflammatory T cells are often associated with increased inflammatory damage, but research of the gut inflammatory and immune response after stroke is still in its initial stage [52]. It would be crucial to understand which metabolites from the gut

*DOI: http://dx.doi.org/10.5772/intechopen.94431*

*Human Microbiome*

models of non-microbial or GF animals were used to determine the influence of

From these gnotobiotic animals, it is possible to decipher mechanisms of communication between specific members of the microbiota and the host organism. Animals lacking microbiota have extraordinarily different development and physiology than animals hosting commensal bacteria. GF animals have impaired immune systems, dysregulated hormone signaling, altered metabolism, and differences in

GF mice show an underdeveloped microglia phenotype, which is manifested by an incomplete immune response to damage. In an experimental stroke model, GF mice showed an incomplete response to brain damage; there was no delineation of the damage locus, which was manifested by an increase in the volume of damage compared to normal animals. Thus it was determined that the microglia of GF

The most common form of dementia is AD, a neurodegenerative disorder associated with impaired cognitive function. This pathology is characterized by extracellular beta-amyloid (Aβ) plaques and intracellular neurofibrillary tangles composed

When studying the connection of microbiota with the brain, one of the tasks is to find evidence of bacterial participation in AD pathogenesis through the formation of amyloid. The results of an experimental model of AD on transgenic mice revealed a tendency to the expression of amyloid precursor protein-β (APP). When these mice were kept in non-microbial conditions, cerebral β-amyloid plaques were less developed than in a normal environment [38]. This experiment indicates that the microbiota is involved in triggering adverse changes in the brains of transgenic animals, but undoubtedly this depends on the species composition and metabolic activity of the bacteria. For example, in AD participants, the gut microbiome has a reduced microbial diversity and taxonomically differs from the control age and sex correspondences of individuals, in particular, in AD compared to the control the number of *Firmicutes* and *Bifidobacterium* was reduced, but the number of *Bacteroidetes* was increased. The potential amyloidogenic properties of gut bacteria were evaluated and the composition of the microbiota and the aggregation of cerebral amyloid-β were also influenced by

Several studies have reported that the microbiome of young mice differs significantly from that of older mice, in particular in the ratio of *Firmicutes* to *Bacteroidetes*. The benefits of the microbiota of young mice were demonstrated in an experiment on stroke models, in which transplantation of the gut microbiota from young to old mice contributed to an improvement in the outcome of

There are some limitations in experiments with GF animals because animals with a diverse microbiota have more developed intestinal epithelium than GF animals, which affects the functioning of the body as a whole. Studying the participation of microbiota in the functioning of the brain may be not always correct in case of comparison of the results obtained in GF and normal animals. The new approach avoids these difficulties by using special mice with a modified microbiota, called the altered Schaedler flora (ASF) mouse line, because they are colonized by only eight

The majority of research showing that microbiota can influence the nervous system has been performed in animals. As such, there is a strong need for well-designed human cohorts. Neuroactive compounds of microbial origin can directly modulate

not only neuronal function and plasticity but also human behavior also [5].

microbiota on the mechanisms of stroke development [33].

neurotransmission from their conventional counterparts [34, 35].

animals is morphologically immature [36].

of hyperphosphorylated tau protein [37].

nutrients [11, 39, 40].

species of known bacteria [42].

stroke [41].

**32**
