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Faecal microbiota transplantation in small animals

Further studies are still required to truly comprehend the use of FMT as a treatment modality in veterinary patients

18 May 2021, at 9:00am

Faecal microbiota transplantation (FMT) is the transfer of faecal or intestinal contents from a healthy donor to a diseased recipient with the goal of restoring or introducing a stable microbial community in the bowel. Although the controversial concept of FMT has gained more attention in recent years, its practice was first described in the fourth century by Chinese scientist Ge Hong as “yellow soup” in the treatment of severe diarrhoea (Zhang et al., 2012). Its use was further adapted in the 17th century by Italian anatomist Hieronymus Fabricius to aid digestion in ruminants (Borody et al., 2004). The first published use of FMT was described in a case series of four patients successfully treated against pseudomembranous enterocolitis (Eiseman et al., 1958), followed by another investigating its specific use against Clostridium difficile infection (CDI; Schwan et al., 1983).

Across the last decade, FMT has been widely practised and developed in human medicine with increasing interest as to how it can be similarly applied to our veterinary patients. This re-emergence of FMT coincides with a paradigm shift in our comprehension and recognition of the body’s microbiome, the preservation of its protective features and antibiotic-conscious treatment regimes.

The gut microbiome

The intestinal tract is home to at least 100 trillion microbial cells, portraying a complex ecosystem crucial to host health, metabolism and the regulation of intestinal-barrier function. The specific balance of microbial diversity varies from individual to individual depending on nutrition, social behaviours and genetics, to give a few examples. This equilibrium can easily be disrupted by antimicrobial drugs, dietary change, vaccination and systemic illness.

Historically, veterinarians have long been unchallenged in prescribing antibiotics and have held little consideration for the potential long-term effects they could impart on the microbiome. Many studies have shown that antibiotics negatively alter gut microbiota, reducing their diversity, bacterial taxa abundance and metabolic performance whilst potentially increasing antibiotic-associated gastrointestinal signs (Suchodolski et al., 2009; Torres-Henderson et al., 2017; Whittemore et al., 2018, Whittemore et al., 2019). It is therefore of no surprising consequence that we are presently and acutely faced with many multidrug-resistant agents. In human medicine the use of antibiotics, especially in early life stages, has been correlated with inflammatory bowel disease (IBD), obesity, autoimmunity and allergic disease (Johnson et al., 2005; Blaser and Falkow, 2009; Ungaro et al., 2014; Saari et al., 2015).

The use of FMT

The exact mechanisms by which gastrointestinal dysbiosis is related to distant organ disease are yet to be understood, but are postulated to relate to substance transfer from the bowel to the systemic circulation, or “leaky gut”. This creates a large window of treatment opportunities with preliminary literature in human medicine demonstrating FMT in the management of autism spectrum disorder, epilepsy, ulcerative colitis and multiple sclerosis (Vendrick et al., 2020; Goldenberg and Merrick, 2021). When looking at the effect of dysbiosis on gastrointestinal disorders, much evidence and therapy in human medicine has investigated the effect of the depletion of favourable bacterial species such as Firmicutes and Bacteroidetes in IBD and CDI (Khoruts et al., 2009).

Faecal microbiota transplantation highlights the role of microbiota-targeted treatment for reimplanting these depleted bacterial species. It suggests that faeces contain a superior and favourable combination of gut bacterial strains that are therapeutic in restoring disrupted native flora for the recovery of gut function. Additionally, faeces contain bile acids, immunoglobulins, vitamins and proteins which could also assist in this process (van Nood et al., 2014). Other commonly used approaches that attempt to “restore” the intestinal microbiota are probiotics, prebiotics and synbiotics.

Consequently, the use of FMT has been broadly defined as therapeutic (to treat clinical signs in ongoing disease), prophylactic (to provide beneficial microbiome characteristics prior to pathogen exposure) or immunogenic (where FMT stimulates pathogen-specific immunity) (Niederwerder, 2018). These latter two applications have been commonly explored in swine and poultry (Siegerstetter et al., 2017; Niederwerder et al., 2018). Small animal studies have mainly focused on FMT’s therapeutic uses to demonstrate positive clinical outcomes, eg the treatment of canine parvovirus (Pereira et al., 2018), eosinophilic inflammatory bowel disease in a dog (Weese et al., 2013), chronic ulcerative colitis in a cat (Furmanski and Mor, 2017) and a case series of eight dogs with Clostridium perfringens-associated diarrhoea (Murphy et al., 2014).

Should I be incorporating FMT in my work-up?

There are currently no widely accepted clinical indications, guidelines or regulations on carrying out FMT in veterinary practice and therefore it should be viewed as a discriminate consideration for veterinarians when no other treatment options exist. With most veterinary studies having taken place in the last decade, there is a heavy reliance on extrapolating techniques from human studies to estimate the manner and success of treatment in addition to long-term sequelae. It must be noted that many human recommendations on FMT are focused on the treatment of recurrent CDI, which is of lesser clinical importance in small animals (Chaitman et al., 2016).

Optimal donor characteristics are also unknown; however, previous studies have collected donor faeces via spontaneous defecation from patients with no pre-existing conditions, at least a six-month history of no antibiotic or other medication use, normal blood parameters and additionally blood and faeces free of infectious agents such as Giardia, helminths, canine parvovirus or distemper virus.

Various techniques for preparation and dosage of the faecal infusion exist. Some veterinary studies have suggested mixing the faeces with tap water or 0.9% sodium chloride solution on an average basis of 10g fresh faeces to 10ml of solution (Pereira et al., 2018; Sugita et al., 2019). Another study created a suspension of 5g frozen donor stool per kilogram of body weight mixed with non-bacteriostatic 0.9% sodium chloride at 60ml for small-breed dogs and 120ml for large-breed dogs (Chaitman et al., 2020). One human protocol has documented mixing 50g of faeces with 250ml of sterile saline (Hamilton et al., 2012). The homogenised mixture is then filtered to remove particulate matter; this can be done inexpensively with muslin cloth. Frozen transplants have been demonstrated to be effective in humans with the use of 10% glycerol to preserve the microbiota in the freezing process (Brandt and Aroniadis, 2013).

There is no ideal or recommended route of administration for FMT; however, it is best performed under sedation either orally (feeding tube placement or enteroscopy) or rectally (faecal enema or colonoscopy) (Chaitman et al., 2016). Many human studies have successfully captured donor faeces in capsules for oral administration; however, the viability of the transplant past the organs of digestion in addition to the time taken to reach the bowel are uncertain. The latter is especially considered when an element of successful therapy is based around the time of contact of the donor faeces with the host’s intestinal tract.

Possible adverse effects and considerations of FMT may include the direct transfer of infectious or pathogenic agents, its cost-effective or cost-benefit value and long-term sequelae (Kelly et al., 2015). Interestingly, new-onset obesity and weight gain have been reported in one woman following FMT from a healthy but overweight donor (Alang and Kelly, 2015).

Conclusion

There has been significant and compelling evidence to document the advantages and successes of FMT in humans with gastrointestinal or distant organ conditions. Ongoing clinical studies and further short- and long-term observations are still required to truly comprehend the use of FMT as a treatment modality and alternative to antimicrobials in veterinary patients. Nonetheless, gut health holds an important role in disease process and propagation and so preserving its healthy function is vital in maximising the overall well-being of our patients.