**2. Human and small animal microbiomes**

The host's first major exposure to a complex microbiota occurs during birth through contact with the maternal microbiome, which represent a primary mechanism for the intergenerational microbiota transfer in mammals and, afterwards, bacterial colonization progresses from childhood to adulthood [24]. The microbiota development is limited to its niches by the host's immune system, along with the host's chronological development, providing early modulation of the host's physiological development and functions of nutrition, immunity and resistance to pathogens at all ages [24].

The most important group of organisms in microbiome studies is called the dynamic symbionts, whose symbiotic nature may vary along a spectrum from mutualism and commensalism to parasitism and amensalism [25]. Usually, microbes perform synthetic or catabolic metabolic activity through direct microbehost interactions. Catabolism and bioconversion of compounds from the diet make nutrients more available to the host through the processes of fermentation, hydrolysis, metabolism of drugs and toxins, among others. Some microbiota members can synthesize important cofactors or bioactive signaling molecules such as vitamins and active amines. In addition, this can trigger changes in the host's gastrointestinal epithelial and immune responses [26].

The combination of factors such as age, genetics, physiological status (including innate and adaptive immune system), lifestyle, diet, host environment and disease status can result in variation in microbiomes between hosts [27]. Human gut microbiota is extremely diverse, with an estimated 1,000 bacterial species in the gut with 2,000 genes per species yields an estimate of 2,000,000 genes, which is 100 times the commonly estimated 20,000 human genes [27]. In dogs, gut

**115**

*Small Animals Gut Microbiome and Its Relationship with Cancer*

microbiome contains around 1,200,000 genes [20] and recent studies suggest that canine and feline gut fecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.*G. major* functional groups related to carbohydrate, protein, DNA and vitamin metabolism, virulence factors and cell wall and capsule) are similar to those of the

Cancer is a complex disease, in which cumulative genetic, epigenetic physiological, immunological and biochemical changes occur incessantly in the tumor tissue, contributing to the complexity of the understanding, treatment and management of the disease. It is estimated that microorganisms could be associated with 15–20%

As mentioned, the microbiota has an essential role in host health, in which a beneficial relationship is established, however, dysbiotic states can trigger several diseases, including cancer. Scott and colleagues proposed that in the etiopathogenesis of cancer, dysbiosis should be considered a persistent exit of the host microbiome from the health-associated homeostatic state (consisting of mutualists and commensals), towards a cancer promoting and/or sustaining phenotype (parasitism or amensalism) [25]. Currently, metataxonomic and metagenomics studies have documented and compared the diversity and abundance of microbes in different parts of the body between healthy and diseased patients. In veterinary medicine, it has been demonstrated a significant difference in the microbial communities in dogs with intestinal and multicentric lymphoma and with colorectal tumors comparing to healthy dogs [12, 13, 30]. However, these studies cannot distinguish whether some alterations in microbiota are causes or effects of cancer, describing

only the different microbial communities found among the study groups.

The microbiome causative role has been demonstrated by controlled pre-clinical studies utilizing germfree (i.e., devoid of any microbiota) mouse models colonized with selected bacteria. For example, several family members of Enterobacteriaceae, including *Escherichia coli*, harbor an island of polyketide synthase (pks) pathogenicity that synthesizes a genotoxin called colibactin [31]. In an experimental study, knockout mice for IL-10 were mono-associated with two strains of *E. coli* that were pks + or Δpks (with and without pks, respectively) and treated with procarcinogenic azoxymethane to induce colorectal tumors to demonstrate that pks play a causal role in tumorigenesis [31]. All mono-associated pks + mice developed invasive carcinoma, in contrast, none of the Δpks mono-associated mice exhibited full invasion [31]. This result suggests that the presence of *E. coli* pks accelerates the progression from dysplasia to invasive carcinoma through the genotoxicity of colibactin, an example of pathway of the microbiota-associated carcinogenesis process. In a recent consensus on the human microbiome role in carcinogenesis, expert opinion was that the microbiome is one apex of a tripartite, multidirectional interactome alongside environmental factors (such as diet, obesity) and an epigenetically/genetically vulnerable host that combine to cause cancer [25]. Gastrointestinal microbiome, which comprises 99% of the microbial mass, not only has the greatest both local and long-distance effects on overall health and metabolic status, but it is also the best investigated microbiome and serves as a model for understanding host–microbiota interactions and disease [32]. Due to its location, gut microbiome has been well studied as a contributor to colorectal carcinogenesis [33]. Other organs with a well-characterized microbiome include the skin and the vagina [34, 35]. The microbiome of each organ is distinct suggesting that effects

*DOI: http://dx.doi.org/10.5772/intechopen.95780*

**3. Microbiome and carcinogenesis**

human gut [28].

of cancers [29].

microbiome contains around 1,200,000 genes [20] and recent studies suggest that canine and feline gut fecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.*G. major* functional groups related to carbohydrate, protein, DNA and vitamin metabolism, virulence factors and cell wall and capsule) are similar to those of the human gut [28].
