Small Animals Gut Microbiome and Its Relationship with Cancer

*Tatiane Moreno Ferrarias Epiphanio and Andreia A.F. Santos*

### **Abstract**

This chapter aims to discuss recent developments in understanding the small animal gut microbiome's relationship with cancer, focusing on animals as well as a model for studying humans. Based on multidirectional interactions between the microbiome, the environment and the epigenetically/genetically vulnerable host, it intends to address the mechanisms by which microorganisms can contribute to carcinogenesis describing the roles of the microbiome directly in the pathogenesis of the disease through complex interactions between the microbiome and the host's metabolic and immune systems. The feasibility for developing new cancer diagnostic and prognostic methodologies plus treatments based on small animals' microbiome profiles are reviewed.

**Keywords:** gut microbiome, carcinogenesis, therapy, dog, cancer

### **1. Introduction**

Much recent medical research focuses on understanding the influences of the microbiome on host health and disease progression such as in inflammatory, metabolic, autoimmune and oncologic diseases [1].

In order to introduce the reader to this chapter, it is essential to clarify some common terms such as microbiota, metataxonomics, microbiome and metagenome. The microbiota is defined as the assemblage of living microorganisms present in a certain environment and is composed by bacteria, archaea, fungi, algae and small protists [2, 3]. Metataxonomics defines the high-throughput process used to taxonomically identify microorganisms in the environment and characterize the entire microbiota, creating a metataxonomic tree [2]. The definition of microbiome includes not only the microorganisms community, but also their "theatre of activity" that involves the whole spectrum of molecules produced by them, including their structural elements (nucleic acids, proteins, lipids, polysaccharides), metabolites (signaling molecules, toxins, organic, and inorganic molecules), and molecules produced by coexisting hosts and structured by the environmental conditions [3]. It stands out that all mobile genetic elements, such as phages, viruses, and extracellular DNA should be included in the term microbiome but are not a part of microbiota [3]. Lastly, the term metagenome refers only to the collection of genes and genomes of members of a microbiota [2].

In humans, as well as in small animals, these complex communities of microbes inhabit predominantly the gastrointestinal tract and oral cavity, but other exposed tissues, such as skin, breast, respiratory and urinary tract, can also harbor unique

bacterial communities [4–9]. The host microbiota and immune system must communicate to maintain a balance between tolerance and activation, otherwise a dysbiotic state can be established and may incite or sustain diseases, such as cancer [10]. Epidemiological associations of abnormal microbiome with gastric, esophageal, hepatobiliary, pancreatic, lung, colorectal, lymphoma and other human and canine cancers have been previously established [11–13].

Neoplastic processes are the leading cause of death in adult dogs [14]. The annual cancer incidence rate is 381 per 100,000 dogs with 4 million new cancer cases per year, similar to the reported rate in humans (454 per 100.000) with 18 million new cancer cases annually [15–17]. In these species, naturally occurring cancers share many features, including clinical presentation, biological behavior, histological features, tumor genetics, and treatment response [18, 19]. Coelho and colleagues showed that the dog gut microbiome has a higher taxonomic and functional overlap with the human gut microbiome than pigs or mice and concluded that findings in dogs may be predictive of human microbiome results [20]. In addition, companion animals represent a special human experimental model in microbiomic investigations due to the exchange of microbes between humans and their pets [21].

In humans, there are some reviews involving microbiome and cancer, but they are scarce in veterinary medicine, with the most reviews covering the microbiome gastrointestinal tract and other diseases [22, 23]. The present article reviews the current status of comparative oncology approaches in human and small animals in the field of microbiome with special focus on carcinogenesis, relationship between specific microbiomes as well as the feasibility of new cancer diagnostic tools and therapies based on microbiome profiles.
