**4. Animal models of gut microbiota research**

Intense animal research is intended to gain insight into understanding the reason why there are obvious differences in the human gut microbiota acquired by the healthy and unhealthy individuals. Although the context of the gut microbiota and brain axis is new, it has been well acknowledged in recent time. It is known that gut microbiota regulates the gut metabolism, and various animal studies have revealed that gut microbiota majorly affects the host immune system as well [38]. A number of animal models have been very crucial in enhancing the understanding towards the gut microbiota-brain axis relationship. Yet there are some disadvantages of using the same method.

First of all, the mouse model which would be the common animal model as it can be a good control for age, gender, diet and treatment factors [3, 39–41]. A study uses the *Lactobacillus rhamnosus* to cause region-dependent alterations in the mouse brain, showed neurochemical and behavioral effects [39]. An alteration in the GABA (γ-aminobutyric acid), the main neurotransmitter of the central nervous system was witness, causing an implication on the pathogenesis of anxiety and depression. However, in the vagotomized mice, the effect was not found, indicating the vagus pathway to be the major pathway between the gut and the brain [39]. In this study the vagotomized mouse model being used well to identify the role of bidirectional pathways. Genetic mouse models are also available to target gene specific manipulation. Many studies using mouse model have revealed the influences on the neurophysiology and behavior, cognition, anxiety and depression related issues. However, the translation of research finding using a mouse model on human is difficult. This is very similar to rat model as well. Studies which target the link between gut microbiota and stress uses hamster model [42, 43]. Hamsters on the other hand are difficult to evaluate as they always live in isolation, which allow them to develop metabolic disorders.

Other than mammals, there are also non-mammalian models such as zebrafish [44–47] and *Caenorhabditis elegans* [48, 49]. *C. elegans* has a specialized microbiome is abundance with bacterial taxa where the presence and the number of bacterial taxa found in each individual worm vary from each other. So, the real challenge of working with this organism is to determine the stability and the connection of its microbial community with the host [48]. Many studies revealed the interaction between the

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

microbiota the host can be achieved by using *C. elegans* as a model organism. In another research paper [50], the effects of host environments on bacterial gene expression was successfully studies using the tractable genetic model, *C. elegans*. In this study, the *E. coli* grown *in vitro* were fed to the host, revealed that the host genetics alters the metabolic pathways of the host. The availability of genetic manipulation is the best feature of *C. elegans* model as this could complement the analysis of individual bacterial taxa. A forward and reverse (two-sided) genetic analysis allows the possibility to characterize the microbial processes and its interaction between the host [48].

Zebrafish on the other hand, has been a well establish model animal in the biomedical research, yet the use of this organism in the gut microbiota research has only happened recently. The sequencing method using the bacterial 16s RNA genes revealed the microbial community comprising the bacterial phylum Proteobacteria, Firmicutes and Fusobacteria at all the life cycle stages of zebrafish [44]. Recent studies, have manage to understand the link between the host, microbes and immune response. It has been suggested that gene editing technology may work by targeting a specific gene-deficient in zebrafish to enhance the understanding of immune responses [51]. This animal can be useful in elucidating the conserved molecular mechanisms as they possess similar gene expression and regulation even with different when the organism is isolated from different environment and having varying physiology [51].

