An explosion of research seeks to understand the complex ecosystem within the gastrointestinal (GI) tract of both humans and their pets, an ecosystem referred to as the microbiome. The development of sophisticated and rapid technology has allowed gene sequencing of this population and its metabolites to move forward at lightning speed.1 Much is to be learned regarding the microbiome for both humans and animals, and this new knowledge will have profound implications for the diagnosis, treatment, and (hopefully) prevention of disease conditions that affect not just the GI tract but many body systems.
The term microbiota refers to the microorganisms in a defined environment, while microbiome includes all of the genetic information possessed by the collective group of microbes. Bacteria in the lower GI microbiome are the most abundant and most intensely studied group to date; however, microbiota also include yeast, viruses, protozoa, and archaea.
In humans, the gut microbiome is diverse and varies between individuals.2 Diversity is described by “species richness” (how many unique species are there?), “species diversity” (how different are they from each other?), and also “diversity of functions” (what different functions of these species are performing?). A healthy adult human typically has more than 1000 different microbial species that make up their microbiota. These can be broadly grouped into Phylums, where Bacteroides and Firmicutes are the most prominent in adults. These groups are not static, with some changes occurring in response to external stimuli. The overall microbiome is typically stable in healthy adults over one- to five-year periods.3,4 It also may change, however, due to impacts of diet, medications, and health status, etc.1 In healthy animals, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria spp. are the most abundant phyla in the microbiome.5
Interaction between the microbiomes of humans and animals occurs regularly. Fecal microbial species and functional capacity have been found to be similar between the canine and feline gut to those of humans.6 Interestingly, pet owning humans may also share microbial communities on skin surfaces with their cohabitating dogs.7 Exposure to environments rich in microbial diversity such as on farms or in pet-owning homes may serve to train a well-adapted immune response and regulate inflammatory responses to inhaled or ingested allergens. Inhibition of this natural exposure and an overly “clean” environment (the “hygiene hypothesis”) is theorized to lead to maladapted pathways that occur in the development of asthma and allergies.8,9 A combination of strategies including controlled natural exposures and appropriate antibiotic use may help restore a microbiome and reduce risk of allergic diseases in humans.10
Gut microbiota are essential for digestive function and health as they constantly generate nutrients from substrates undigestible to the host. Microbiota in the lower GI are able to digest substances (including fiber) to produce beneficial postbiotics such as short chain fatty acids, which serve as a preferred energy source for intestinal mucosal cells that make up the inner lining of the GI tract. Vitamins such as vitamin K, cobalamin (B12), and folate (B9) are also produced. The microbiome stimulates the production of mucous and promotes intestinal cell turnover while stimulating the gut immune system.11 Normal bacteria that reside within the GI tract take up space and utilize nutrients that otherwise may be harnessed by opportunistic, potentially harmful bacteria. Numerous complex interactions occur within the gut microbiome that promote healthy balance and tolerance of microbes and their metabolic byproducts, which protect both the host and the resident microorganisms.12
Many consider the gut microbiome as another “organ” that can fail when imbalanced or in times of critical illness.13 The microbiome may become imbalanced and no longer metabolize diet nutrients resulting in the potential for malnutrition and contribute to disease conditions.14 This state of dysfunction may be described as “dysbiosis,” which is defined as alterations in microbial composition and/or diversity.5 Failure of this “organ” system may cause deterioration of the mucosal barrier allowing invasion of bacterial pathogens or a breakdown of the normal protective immune responses from the GI tract.15 This failure may harm the host by promotion of inflammation or potentially enabling direct invasion of organisms causing sepsis.16-19 Microbial alterations in the microbiome has been linked to inflammatory bowel disorders in both dogs and cats.20 In dogs, concern for systemic bacterial invasion (septicemia) has been noted in cases of severe hemorrhagic gastroenteritis.21
Microbiome of Dogs and Cats
The composition of the microbiome varies across the GI tract and is not uniform, as distinct communities have been identified in the mouth, esophagus, and stomach. Even within one location, subpopulations may exist, influenced by anatomical characteristics, pH, oxygen tension, and variation in nutrients available. Microbes are also affected by diet, use of antimicrobials, mucus, and immune function. The small intestine microbiome appears more sensitive to diet changes and is populated with mostly aerobes and facultative anaerobes, while in the cecum and descending colon, primary populations are mostly facultative anaerobes and strict anaerobes, reflecting the decreasing availability of oxygen for metabolism.22
Diets in Veterinary Care and Microbiome
Changes to the microbiome in pets may occur rapidly in response to dietary intervention. Variations in the amount of carbohydrate (including fiber), protein, and fat that is fed to cats and dogs can have a significant impact on their intestinal microbial balance in a short period of time. Studies have noted alterations in species diversity and abundance when diets were changed from extruded dry foods to cooked or raw diets in both dogs and cats.23-25 Further studies are required to learn more about the long term potential implications for gut health and possible benefits or adverse effects of diet form and nutrient profiles.
Prebiotics, Probiotics, Synbiotics, Antibiotics and Fecal Microbiota Transplantation (FMT) in Veterinary Care
Support for the microbiome has focused on prebiotics, probiotics, synbiotics, and even fecal transplantation in humans and pets.
Prebiotics are non-digestible compounds that when consumed serve as substrates to favor the growth of beneficial microbes. They are not readily digestible to the host animal allowing them to reach the lower GI tract and interact with local microbes. These materials can be fermentable or nonfermentable, and/or soluble or insoluble. Prebiotics are mainly plant-derived fibers and include inulin, fructo-oligosaccharides. and galacto-oligosaccharides.17 These nutrients may favor the metabolic activity of beneficial bacteria in the microbiome, including Bifidobacterium and Lactobacillus species.
Many prebiotics lead to the production of short chain fatty acids (SCFA), a group of small acidic compounds that are produced through microbial fermentation which have been shown to benefit hosts – this is an example of a postbiotic. SCFAs maintain health through several mechanisms including reducing inflammation and lowering gut pH to inhibit growth of pathogenic or harmful microbes.26,27
Other functional materials important for digestive health include soluble fibers such as from psyllium, beet pulp, oats, barley, and other plant foods. These may serve to improve stool quality by binding excess water, promoting the thickness of the mucous layer in the GI tract and stimulating intestinal cell turnover.28 Most commercial therapeutic diets aimed at managing GI diseases will contain increased prebiotic fiber content while homemade diets may be designed by a veterinary nutritionist to include strategic fibers either in whole foods or with supplementation to the diet.29
Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.”30 Probiotic veterinary products currently may include Lactobacillus sp., Bifidobacterium sp., Enterococcus sp., or Saccharomyces boulardi. Potential benefits of probiotics include replenishment of beneficial bacteria, modulating the host immune system, and inhibition of pathogenic bacteria by competition for adhesion sites or nutrients. Probiotics may also enhance mucosal barrier function by stimulating mucous or antimicrobial peptide production.31,32 Probiotics should be chosen based on proven effectiveness in scientific studies beyond even the species level, down to the specific strain delivered. Some commercially available products have demonstrated positive effects for different GI conditions in dogs and cats.33-35
This term refers to the combination of a prebiotics and probiotics together in one food or supplement. Use of a synbiotic in shelter dogs in a randomized, double-blind, placebo-controlled trial has shown a significant decrease in the incidence of diarrhea.36 Supplementation of synbiotics has also been demonstrated to reduce antibiotic associated adverse GI signs in dogs and cats.37 Client owned cats with chronic diarrhea had improvements in fecal scoring demonstrating a positive benefit when supplemented with a commercial synbiotic.38 Research is ongoing on this combination in veterinary products.
Using Antibiotics with Caution
Antibiotics are drugs that may selectively or non-selectively result in bacterial species inhibition or elimination within the host. Antibiotics should not be used as first line treatment for cases of dysbiosis, as approximately 60 to 70 percent of veterinary patients with chronic enteropathies may respond to diet change alone.39 Use of antibiotics may resolve initial clinical signs; however, long term alterations to the gut microbiome may persist including reduction of diversity and/or change in predominant species.40,41 Inappropriate antibiotic use may also lead to cases of resistance; thus, the decision to use them in a particular case must be made carefully. Guidelines have been suggested for veterinarians on the appropriate use of antibiotics in dogs with GI disease.5
Fecal Microbiota Transplantation (FMT)
Fecal Microbiota Transplantation (FMT) involves the infusion of a suspension of feces from a healthy donor into the GI tract of another with the goal of restoring a stable and healthy microbiome. Numerous success stories exist for treatment of Clostridium difficile infection and inflammatory bowel disease (IBD) in humans with FMT. A few reports of success are documented in small animals.42,43 As FMT does not address the underlying disease process but rather attempts to correct the associated dysbiosis, relapse rates may be higher in patients with more advanced GI pathology. Currently, there are suggested guidelines published for the use of FMT in dogs and cats.44
As knowledge continues to grow regarding the complex microbiome within the GI tract, newer diagnostics and treatments to include supplements and/or medications will continue to develop, directed at supporting optimal balance in the GI tract and promoting health of the microbiome. It is becoming increasingly evident that maintaining health of this organ system is crucial for both human systemic health and that of pets.