Fecal Microbiota Alterations in Illness and Efficacy of Fecal Microbiota Transplantation in Treatment of Inflammatory Bowel Disease in Dogs
Gastrointestinal dysbiosis has been noted in a myriad of conditions in companion animal and human medicine, including inflammatory bowel disease (IBD), immune mediated disease, and critical illnesses. The literature on the microbiota in conditions other than IBD, as well as manipulation of the microbiota through fecal microbial transplant (FMT) on dogs is limited. As a result, an objective of this thesis was to compare the fecal microbiota of healthy dogs, dogs with IBD, and dogs with critical illness. Additional objectives were to compare the efficacy FMT in addition to standard treatment (hypoallergenic diet and immunosuppressive medications) in dogs with IBD versus standard treatment alone in inducing clinical remission, to describe the alteration in the fecal microbiota in dogs undergoing medical therapy for IBD, and to detail a protocol for preparation and administration of FMT in dogs. In the first study, ten healthy dogs, nine dogs with IBD, and 29 dogs with critical illness (nine dogs with immune mediated hematologic disease (IM), and 20 dogs with other critical illness (NIM)) were recruited. DNA extraction from fecal samples and PCR analysis of the 16S gene were subsequently performed, followed by sequencing using an Illumina MiSeq platform. There was a significant difference between groups for community structure (Yue and Clayton index, p=0.039), and community composition (Jaccard index, p<0.001). The Jaccard index was significantly different between healthy and diseased (IBD, NIM, IM) groups (p<0.001), but not between individual diseased groups (p>0.05). In the second study, 13 client-owned dogs with IBD were enrolled. All patients received corticosteroid therapy and a hypoallergenic diet; patients were randomized to receive either placebo or fecal microbial transplant (FMT). Measured outcomes included the canine chronic enteropathy clinical activity index (CCECAI) along with measurement of serum albumin, C-reactive protein (CRP), and cobalamin levels at 1 week, 1 month, and 3 months after enrolment. Fecal microbiota were analyzed following DNA extraction and profiling using 16S amplicon sequencing. The CCECAI significantly decreased over time regardless of treatment group (p = 0.001). Dogs receiving FMT had improved disease severity scores when assessed 30 days after enrolment (p=0.02), whereas dogs administered a placebo with standard therapy did not (p=0.61). However patient outcome was not affected as differences between treatment groups in the CCECAI (p = 0.735), albumin (p=0.43), CRP (p = 0.287), or cobalamin (p = 0.601) were not observed after 90 days of treatment. No adverse effects were reported after FMT. The alpha and beta diversity measurements were not significantly different between pre and one week post FMT samples (p > 0.05). Fecal samples were significantly enriched in Faecalibacterium (p=0.047) one week following FMT. In conclusion, dogs with IBD and dogs with critical illness had a similar fecal microbiota community membership, which was significantly different from healthy dogs. Additionally, FMT was an easily applicable treatment option in canine IBD which resulted in improved disease severity scores early after therapy whereas placebo treatment did not, although it did not change longer term patient outcome or fecal microbiota diversity in dogs with IBD in this study.