There is growing interest in the microbiota and its role in pet health, as increasing research into the gastrointestinal microbiota starts to identify the important role it has to play in general health and well-being in both humans and animals. In fact, the intestinal microbiota is now considered to be a metabolic organ with important impacts on host health (Suchodolski, 2018). So, what constitutes a healthy microbiota, and what factors can influence its composition? An impaired microbiota can lead to gut dysbiosis – but what is the impact of this and how may we be able to ameliorate this with management strategies, now and in the future?
What are the roles of the intestinal microbiota?
There are an estimated 100 trillion microbial cells in the gastrointestinal tract – tenfold more than the number of host cells (Suchodolski, 2018). They have a number of roles. They can influence both the systemic and gastrointestinal immune system of the host. They assist in disease resistance and defence against enteropathogens, thought to be due to creation of a physical barrier to pathogen colonisation, competition for nutrients and production of antimicrobial substances (Caddick, 2020). They also provide nutritional benefits (Suchodolski, 2018). For example, fibre sources such as inulin from chicory and beet pulp are fermented by bacteria in the large intestine to produce short chain fatty acids (SCFAs), which have a number of potentially beneficial roles in the gastrointestinal tract, including acting as energy sources for the host, regulating intestinal motility and providing growth factors for epithelial cells as well as reducing ionised bile acids, long chain triglycerides and ammonia (colon irritants), and reducing overgrowth of potentially pathogenic bacteria such as Clostridium spp. They also have direct anti-inflammatory properties through expansion of immunoregulatory lymphocytes (Suchodolski, 2018). Intestinal microflora also hydrolyse urea, modify the metabolism of cholesterol and bile salts, and synthesise vitamins including B12, folic acid and biotin (Jean-Phillippe, 2012). In fact, gastrointestinal bacteria are solely responsible for the conversion of primary bile acids to secondary bile acids (Suchodolski, 2018) – one example of how important they are to the physiology of companion animals and humans.
Does the intestinal microbiota have roles beyond the gut?
There is accumulating evidence that the intestinal microbiome has impacts on the body beyond its local effects of digestion and protection within the gastrointestinal tract. In fact, the health of the intestinal microbiome is now thought to play a role in the development and progression of obesity, atopic dermatitis and neoplasia, as well as having an impact on cognition and renal function (Valdes et al., 2018; Geva-Zatorsky, 2018; Caddick, 2020). Thus, maximising health of the intestinal microbiota could have key roles in overall health of the animal.
What constitutes a healthy microbiota?
Most research investigating the role of the microbiome has been conducted in humans, but as technologies advance and we realise the importance of the gastrointestinal microbiome, increasing resources are being invested in studying it within the veterinary community, although this research comes with a number of challenges. Traditional techniques to gain information about the microbiome composition have included culture, but this is thought to be suitable for only approximately 5 percent of the gastrointestinal microbiome (Suchodolski, 2018), and does not give consideration to elements such as the postbiotics produced by bacterial metabolism. Every individual has a very different microbiome – differing both in the balance and the species and strains of bacteria within the gastrointestinal tract (Suchodolski, 2018). We do see clear differences between the microbiome present in a healthy animal and that of a diseased animal, and over time, certain disease phenotypes demonstrate specific patterns of microbiome shifts (Suchodolski, 2018). However, further information about both the microbial composition and their functions, including their metabolic activity and immune interactions, is needed to define what is “healthy” or “unhealthy”.
A dysbiotic microbiome may impact the host in functional or immunological ways that can be deleterious – for example, due to the production of toxins or reduction in anti-inflammatory metabolites (Suchodolski, 2018). Dysbiosis is often associated with acute and chronic gastrointestinal disorders (Suchodolski, 2018), although in the majority of cases it is still unknown whether dysbiosis is the cause or result of disease. As mentioned above, it also appears to play a role in extraintestinal diseases including atopic dermatitis and obesity (Valdes et al., 2018; Geva-Zatorsky, 2018). It is becoming increasingly evident that a bidirectional communication exists between the gut microbiota and the brain (the microbiota-gut-brain axis). Dysbiosis has been shown to affect behaviour and be involved in the pathogenesis of neurological diseases including Parkinson’s in humans, and to correlate with aggressive behaviours in dogs (Geva-Zatorsky, 2018).
However, it can be difficult to correlate dysbiosis with a clinical picture, and its contribution to disease does seem to vary between different patients. There is some evidence that genetics plays a role in influencing the microbiota composition, but the environment appears to be the major factor. Lifestyle and environmental triggers such as medication use, especially antibiotic use, as well as diet can influence the microbiota and also impact upon the likelihood of dysbiosis developing (Suchodolski, 2018). Antibiotics and their potential influence on dysbiosis is particularly complex.
Veterinarians may give antibiotics to treat an animal with chronic diarrhoea, but by doing so could potentially induce or worsen any dysbiosis, as well as causing further diarrhoea (Suchodolski, 2018). Antibiotic-induced dysbiosis has the potential to trigger longer-term problems. In humans, the development of intestinal microbiota when young has a significant impact on health later in life, and antibiotic-induced dysbiosis in early childhood has been identified as one of the most important risk factors in the development of allergies, obesity and inflammatory bowel disease in adults (Suchodolski, 2018). Further understanding of dysbiosis, the factors that influence it and the potential clinical impacts for companion animals is crucial to help us more fully understand both the therapeutic strategies we currently use in veterinary practice to help treat acute and chronic gastrointestinal disorders and how we can influence the microbiome beneficially.
What can we currently do clinically?
There are four main ways we can currently influence the microbiome in veterinary medicine: antibiotics, diet and prebiotics, probiotics and more novel therapeutic strategies such as faecal matter transplantation. Given that every individual has such a varied microbiome, companion animal patients may clinically have very different responses to each of these strategies. The traditional approach of antibiotics has increasing concerns around it – due to both antibiotic resistance and the potentially negative impacts it appears to have in inducing major shifts in microbiota and potentially causing diarrhoea as an unwanted side effect. At the moment we have no way to block the effects of antibiotics on dysbiosis. Nutritional support in the form of increased fibre and prebiotics, and probiotics, are attracting increased interest. A number of commercially available diets containing prebiotics are available, particularly those tailored towards support in gastrointestinal disease. There is also a range of veterinary-authorised probiotic products, although there is great variability in the quality and potential efficacy of these products, so clinicians are encouraged to assess the evidence for the particular strain and preparation of probiotic being marketed before selecting it for use. In addition to this, consideration of advice to owners to help minimise stress, which may adversely impact microflora diversity and stability – for example, in incidences of environmental changes – may help support the GI microbiome. Appropriate guidance to owners during any dietary changes, including a gradual diet transition and considering use of gastrointestinal supportive products during this switch, may also help minimise changes in microbiome stability (Caddock, 2020).
We should now start to recognise the importance of the gastrointestinal microbiota as an organ in itself, and consider the significant functional and immunological roles it may have in both gastrointestinal health and overall health and behaviour. Many conditions we previously or may still treat with antibiotics may not actually be conditions where we should use antibiotics as a first line approach and there are concerns that antibiotic administration in itself may induce dysbiosis. Nutritional support in the form of prebiotics and supplements such as probiotics show great potential, although more controlled studies and evidence are needed to identify how we may optimally support the gastrointestinal microbiome.