**2. The bidirectional communication in microbiota-brain axis**

Researches on gut microbiota-brain communication focused on its effects towards digestive functions. However, the current interest in microbiology and neuroscience has given way to understand the psychophysiological consequences of gut-brain or brain-gut as a two-way network [3, 4].

The gut microbiota-brain axis is the term referring to the two-way communication between the gut and the brain [5–8]. More importance is given to elucidate the function of microbes in the gut microbiota-brain axis link as the microbiota can be altered intentionally. The exact mechanism of communication between the gut microbiota and brain has yet to be elucidated, however, the multiple pathways have been identified. The gut microbiota possibly causing an effect on the brain function through the nervous system, endocrine system, immune system, and metabolic system [8].

The bidirectional communication is important in analysing the gut-brain signaling pathways which regulate the host brain and behavior [8]. This bidirectional communication pathway is consisting of the central, enteric, and autonomic nervous systems and the hypothalamic-pituitary-adrenal (HPA) axis. These pathways use the metabolites and the by-products of gut microbes as a communication factor [9]. In recent time, active researches on gut microbiota-brain axis targets the main pathways of the vagus nerve system, the immune system, the neuroendocrine systems, the neurotransmitters and the metabolites [10]. The vagus nerve is responsible in making a physical connection of the gut-brain combo, whereby it allows the brain to sense the gut environment. The vagus nerve extends from the brain to the gut, carrying motor signals and controls the internal digestive, heart and respiratory rate. These motor signals are also transferred to the intestinal cells causing an effect on the gut microbiota [11, 12].

Next, the connection between the gut microbiota and the host immune system is another key research area as studies showing inflammation in neurological and metabolic related disorders [13–16]. The development of low-grade systemic inflammation is associated with impairment in immune response and dysbiotic microbiota. The dysbiosis can regulate on both the innate and adaptive immunity and cause an effect on the gastrointestinal tract and throughout the body. This has been clearly proven in autism spectrum disorders (ASD), epilepsy, Alzheimer's disease, Parkinson's disease and cerebrovascular diseases [16].

Recent findings have showed that the gut microbiota triggers the HPA axis. This pathway controls the neuroendocrine system that modulate stress response, mood and emotions [17]. Evidences shown that microbiota controls the gut hormones and then later regulates the hormone responsible for stress, mood and emotions [17–19]. Gut hormones proven to involve in the physiological processes causing anxiety and depression [18]. A disruption in this bidirectional pathway has been linked with depression, irritable bowel syndrome (IBD) [19] and obesity [18]. These evidences clearly show that gut hormones are potentially regulating the well-being of the host.

#### *The Interaction of Gut Microbiota-brain Axis in Relation to Human Health with the Use… DOI: http://dx.doi.org/10.5772/intechopen.105866*

The gut microbiota on the other hand, has a major function in the metabolic pathway, which involves energy homeostasis and metabolite production. Animal studies have shown evidence on the ability to produce and metabolise a range of neurotransmitters [1]. A number of neurotransmitters which function as hormones including dopamine, serotonin, noradrenaline, gamma-aminobutyric acid (GABA) has been identified in the context of gut microbiota and brain axis network. These are also known as the hormone-like neurotransmitters which are not only produced in the gut but they do play role in the microbiota. Various factors such as diet, drug, or disease can potentially change the composition of gut microbiota and at instant alters the hormones [20]. In the context of diet, the composition and activity of the gut microbiota can be majorly affected due to the type of food consumed by the host [20].

### **3. Gut microbiota affecting human health**

The alterations of the gut microbiota have the potential to affect the human health and causes various common health as well as major disorders. Firstly, studies have shown the link between the gut microbial community with the common metabolic diseases including obesity, type-2 diabetes, non-alcoholic liver disease, cardiometabolic disease, and malnutrition [21]. This study has attempted to reveal the connection between abnormal gut microbiota composition and it by products to the dysmetabolism in the diseases mentioned earlier.

The number of cases related to obesity has increased tremendously in the developed countries over the past years [22]. Individuals with obesity has been reported with low microbial gene richness with a relative increase in adiposity, resistance towards insulin, and inflammation [23]. The use of antibiotics before and during pregnancy or in childhood may cause a receding microbial richness of infant and children, increasing the chances of acquiring early-onset of obesity [24, 25]. It was not proven that the receding microbial community is the primary causal factor of obesity, however, it has been shown that low microbial gene richness could be improved with dietary interventions [26].

Type 2 diabetes (T2D) and prediabetes have potential link with altered gut microbiota. An epidemiological study comparing individual without colectomy and patients with total colectomy showed a higher risk of acquiring T2D [27]. This disease has been showing an increased prevalence, especially targeting the adult population and leading to endocrine disorders [28]. Studies have been targeting the products of gut microbiota which may involve in elevating the glucose level in blood. In another study, the gut microbiota of prediabetes individuals shown that there is a reduction in number of *Akkermansia muciniphila* and increase in the number of bacteria proinflammatory potentials [29, 30]. *A. muciniphila* is a butyrate-producing bacterium, the reduction on its abundance in the gut may lead to aggravation of opportunistic pathogens [31, 32]. The challenge in revealing the significance of altered gut microbiome to T2D is that the patients are heavily medicated where that would be another main factor causing a dysbiosis to the gut microbiome. That is the reason for using prediabetes individuals as the drug-naïve targets [29].

The gut microbial dysbiosis can also be linked to cardio-metabolic diseases (CMD). Study [33] reported an increase level of *Enterobacteriaceae* and oral cavity species in the gut microbiota of individuals with CMD compared to healthy controls. The microbiota of these individuals has reduced *Bacteriodes* spp. and anti-inflammatory species. In another report, a dysbiotic gut shows potential link to ischaemic heart failure with an elevated level of genes responsible in the systhesis of Lipopolysaccharides [34]. This shows that a disruption in the gut microbiome leads to heightened fatty tissues in the host. A sequencing study done by [35] showed a link between microbiota and atherosclerosis, and later, trimethylamine N-oxide (TMAO), a metabolite from the gut microbiome found to be the causal link to CMD [36].

The microbiota-brain interaction clearly shown is effects on the progression of brain disorders. The development of Parkinson's disease has been linked with formation of protein misfolds in alpha synuclein caused by *Escherichia coli. E. coli* was found to produce curli, a protein which causes misfold in other proteins and this error is transmitted to the brain via the vagus nerve [37]. The onset of the ASD has been suggested to cause by segmented filamentous bacteria in the gut. Occurrence of infection during pregnancy causes the bacteria to trigger the T-helper cells to produce immune molecules which later travels to the fetus's brain and provoke autism like behaviors [20].
