F. Gaschen
School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
Introduction
The intestinal microbiome is a complex system consisting of bacteria, fungi, protozoa and viruses. In mammalians, intestinal microbiota outnumber the host cells by a factor ten. In dogs, more than 10 different bacterial phyla have been described with Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria being the most commonly represented. These microbiota provide essential benefits to the host health: they play a key role in the development and function of the gastrointestinal immune system, protect against enteropathogens, support the epithelial integrity and promote nutrient supply to the enterocytes. Recent studies have highlighted the importance of metabolites produced by intestinal microbiota, also known as the intestinal metabolome, and their contribution to host physiology. Therefore, the intestinal microbiome is considered to be an essential organ in mammalians. Consequently, changes in the intestinal microbiome are often paralleled by changes ranging from inability to process and absorb nutrients, to absence of important metabolites or appearance of undesirable metabolites in the intestinal mucosa with possible effects for instance on the enteric nervous system and higher centers. In human medicine, a large body of research has documented changes affecting intestinal microbiota and associated metabolites in diseases of the gastrointestinal tract and liver, but also in diseases affecting organs outside the digestive tract such as obesity, behavioral and psychiatric disorders.
Definition
Fecal microbiota transplantation (FMT) consists in transferring fecal microbiota from a healthy donor to a host with an abnormal intestinal microbiome. While the technique has been known and used for many centuries in various indications, it has regained popularity in recent years for the treatment of Clostridium difficile colitis in people, and its use has been approved by the Food and Drug Administration for that indication. The goal of FMT is to provide a healthy and viable sample of fecal microbiota to repopulate the recipient’s large bowel. In addition, FMT also delivers essential metabolites such as secondary bile acids that may be lacking in the host.
Indications for FMT in Small Animals
There are very few published data on the use of FMT in dogs and cats. Apart from a few abstracts presented over the last 6 years, there is only one published study on the use of FMT as an adjunct to therapy in puppies with parvovirus infection. In that study, FMT was applied at patient admission and repeated every 48 h as needed. The results were encouraging since FMT led to faster recovery from diarrhea and shorter hospitalization time. Investigations on the value of FMT in dogs and cats with chronic enteropathies (such as IBD) or in animals receiving antibiotics are underway at different centers.
Donor Selection
It is a complex process in human medicine, where fears of transmission of known and yet unknown diseases are high. Overall, two options exist: (1) to obtain fresh feces from a family member or friend of the patient or (2) to order frozen feces from a fecal bank where fecal donors are subject to very detailed investigations of their medical history and lifestyle prior to being approved. Fresh feces are most commonly used in small animals, and donors should be clinically healthy with a normal body condition score, not prone to digestive diseases such as vomiting and diarrhea, and screened for intestinal parasites (nematodes, cestodes and protozoa), and ideally for enteropathogenic bacteria (PCR). The author also determines a dysbiosis index in order to check the health of donor’s fecal microbiome. Moreover, fecal donors should not have received any antibiotics in the 3–6 months prior to collection. Additionally, in cats, FIV and FeLV testing is required.
Preparation and Administration
Fresh feces should be processed within 6–12 hours of collection. Numerous protocols are used for preparation of FMT solution. The author adapted current state-of-the- art processing from human medicine in his lab. The feces are weighed and diluted with saline (volume=4 x fecal weight), then thoroughly mixed prior to filtration through a layer of gauze. Immediately following preparation, the fecal solution is administered to the recipient in the proximal part of the descending colon via enema (or via colonoscopy) at a dose of 5 ml/kg. Although there is debate about the necessity to administer a sedative to recipients prior to the enema, it may be useful, particularly in difficult dogs and cats. In order to avoid rapid evacuation of the transplanted solution, recipients should be kept quiet for 30 min after administration. The need for repeat FMT depends on what disease is being treated. It is probable that dogs and cats with chronic enteropathies would benefit from repeated FMTs, while a single or two FMTs might be sufficient to help with acute diarrhea. Oral administration of FMT through a nasoesophageal tube or inside gelatin capsules is another delivery method.
Outlook
Several studies are ongoing on the use of FMT in dogs and cats, and publication of results can be expected with 1 to 2 years. If their outcome is positive, it is likely that FMT will gain popularity in the treatment of acute and chronic GI disorders. In the future, it is possible that FMT will be recommended in small animals as part of the treatment of diseases primarily affecting organs outside the GI tract. Examples could include hepatic encephalopathy, obesity, behavioral disorders, etc.
Additional Reading (Selection)
1. Al Shawaqfeh MK, Wajid B, Minamoto Y, et al. A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy. FEMS Microbiol Ecol. 2017;93(11). [Open Access]
2. Barko PC, McMichael MA, Swanson KS, and Williams DA. The gastrointestinal microbiome: a review. J Vet Intern Med. 2018;32 (1):9–25. [Open Access]
3. Chaitman J, Jergens A, Gaschen FP, et al. Commentary on key aspects of fecal microbiota transplantation in small animal practice. Veterinary Medicine: Research and Reports. 2016;7:71–74 [Open Access]
4. Pereira GQ, Gomes LA, Santos IA, et al. Fecal microbiota transplantation in puppies with canine parvovirus infection. J Vet Intern Med. 2018;32(2):707–11. [Open Access]