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Common Definitions

1.1 Microbiome

There are multiple functional definitions of the term "microbiome." According to the Human Microbiome Consortium, the microbiome is considered as the community of all microbes recovered from a particular habitat or ecosystem [1]. These microscopic communities, including bacteria, fungi, and viruses, can be found in all living things, including plants, and are found in every different imaginable habitat, from lifeforms to soils and bodies of water [2, 3]. Microbiomes can be found on outer surfaces, particularly as biofilms, and within several body systems of animals including the respiratory tract, reproductive organs, integumentary, oral cavity, urinary tract, neurological pathways via the brain-gut axis, and the gastrointestinal (GI) tract. Over 30 trillion microbes may reside within the GI system alone [4, 5]. This list is not exhaustive, as this area of knowledge is relatively novel, and innovations allow us to discover microbiomes in organs and systems once thought to be sterile. The total cumulative microbiomes in a human host may weigh as much as 1-3% body mass [4].

While some common trends are being observed in current research, microbiomes are unique for each individual with their diversity and density affected by several intrinsic (genetics, age, sex) and extrinsic (environment, physiological state, antibiotic therapy, health and nutrition) factors [6]. These incredibly diverse communities shape the health of the host and influence its physiology, through multiple complex pathways, including influencing remote organ and immune responses. A main focus of research is on the microbiomes of the GI tract, and how perturbations of these complex communities are associated with multiple health conditions in humans: depression, autism spectrum disorder, oral health, chronic obstructive pulmonary disease (COPD), asthma, pneumonia, dermatological, obesity, cardiovascular, diabetes, rheumatoid arthritis, hepatic associated disorders, cancer, inflammatory bowel disease (IBD), and infection due to bacterial translocation [4-7]. Microbiome communities affect the status of, and rely on, each other for daily functions, communicating through the release of metabolites - products of microbial fermentation [8]. One recognized influence is the cumulative genetic material, the metagenome, of all the microbes in one animal's singular microbiome. A metagenome may contain over 200 times the number of genes in a host's genome; therefore, the level of influence these genes have over host gene expression is one explanation for the microbiota influence on the host's physiological systems [8].

The development of new innovative research tools allows us to see, understand, and evaluate previously unidentifiable concepts regarding the body's microbiomes. Some obstacles that remain with identifying and determining the effects of microbiomes are reproducing their environment, including food sources, to enhance growth and preventing the death of the microbes when sampling. Research is also limited at this time, with many research projects utilizing small study groups, which are not always representative of the wider population, or reproducible in future projects. This is a common limitation for quantitative research [9].

1.2 Microbiota

The microbiota may be defined as the individual bacteria, fungi, viruses, and protozoa that can be found in a microbiome community. Microbes pre-date the Earth's eukaryotic biodiversity and are numerous, diverse, and ubiquitous. They have adapted to live in extreme environments such as the high pressure, as in the deep ocean, extreme heat, or chemical exposure. Different types of bacteria survive in both aerobic and/or anaerobic environments. Environmental differences are one reason that it has been difficult to identify microbiota in discovered and undiscovered communities [8]. Those that live in an anaerobic environment may have a shorter survival rate when removed, for example in biopsy samples, and then brought into an aerobic environment. It is estimated that only 20-30% of organisms are culturable, which leaves a large group of microbiota that are unidentified through routine culture [10]. The main phyla composing the gut microbiome vary from species to species, but Fusobacteria, Bacteroidetes, and Firmicutes, as well as, to a lesser extent, Proteobacteria and Actinobacteria, are typically prevalent in dogs and cats [3, 11].

Communication occurs between the microbes within their microbiome and with host body systems, which in turn can change or influence the physiology of the host. The host relies on the microbiota to complete functions that may not be encoded in their genes to complete [5]. The roles of microbiota are complex and may change as resource availabilities change [8]. Currently, we understand that microbiota plays roles in the production of vitamins, mineral absorption, structural integrity of barriers, metabolism of nondigestible products and provision of energy sources (short-chain fatty acids - SCFAs), interactions with or involved in the production of chemical and neurotransmitter metabolites affecting other organs of the body (bidirectional axis), host genomic expression, inflammatory processes, intestinal permeability, immune function, and food intake and energy expenditure [4, 6, 8, 11-16].

1.3 Pathogens

Pathogens are defined as a biological agent that causes disease or illness to its host. Although in the minority, these microbes are generally known to cause illness, at least in certain circumstances. Pathogens can be divided into five groups: viruses, bacteria, fungi, protozoa, and helminths [17]. Characteristics of pathogens are the mode of transmission, mechanism of replication, pathogenesis (how it causes diseases), and ability to elicit a response. Depending on the pathogen, replication may occur in the intracellular and/or extracellular compartments, while host defense mechanisms work to destroy the pathogen and stop its growth. Common canine and feline pathogens are summarized by group in Table 1.1.

Pathobionts are commensal microbes that can be present at low levels in healthy microbiomes without causing harm to the host but can be pathogenic under certain circumstances [10]. While a general previous concept was a simple overgrowth of a pathogenic bacteria was the cause of dysbiosis, new information shows that a barrier dysfunction plays a larger role in pathogenic bacteria being allowed to either colonize or translocate (cross the surface of an epithelial barrier) causing illness in the host [10, 17]. In some circumstances, it may be a combination of genetics along with the presence of specific microbiota or metabolites that lead to disease or illness in the host. The immune response cannot eliminate most pathogens, and most pathogens are not universally lethal as this would affect the long-term survival of that pathogen [17]. However, some pathogens may cause an attack on the immune response that can affect other microbiomes in the body and may be detrimental for the host [25, 26].

Table 1.1 Common canine and feline pathogens.

Source: Adapted from Alexander et al. [18], Inpankaew et al. [19], Day et al. [20], Riley et al. [21], Millán and Rodriíguez [22], Biek et al. [23] and Villeneuve et al. [24].