Fecal microbiota transplantation as a new treatment for canine inflammatory bowel disease

Abstract

In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p<0.05). The changes in clinical signs (e.g., vomiting, diarrhea, and weight loss) were evaluated according to the canine inflammatory bowel disease activity index. The score of this index significantly decreased in all dogs (p<0.05) with improvements in clinical signs. These improvements were related to the changes in the proportion of microbes, particularly the increase in Fusobacterium. The dogs with IBD showed a lower proportion of Fusobacterium than healthy dogs. This suggests that a low proportion of Fusobacterium is a characteristic feature of canine IBD and that Fusobacterium is involved in this disease. The results of this study may help elucidate the pathogenesis of this disease and its association with Fusobacterium.

Keywords: Fusobacterium; canine; fecal microbiota transplantation; inflammatory bowel disease; inflammatory bowel disease activity index; microbiome.

Fig. 1.

Clinical observation according to the canine inflammatory bowel disease index (CIBDAI). The normal range is 3 or less. The post-fecal microbiota transplantation (FMT) CIBDAI score is significantly lower than the pre-FMT score (p<0.05). The data were analyzed using a t-test with R (version 2.8.1).

Fig. 2.

Assessment of clinical signs using the canine inflammatory bowel disease index (CIBDAI). The CIBDAI is based on six criteria, each scored on a scale of 0–3: attitude/activity, appetite, vomiting, stool consistency, stool frequency, and weight loss. The total composite scores were evaluated as follows: 0–3, clinically insignificant; 4–5, mild; 6–8, moderate; and 9 or higher, severe [28, 29].

Fig. 3.

Rarefaction analysis of the V3–V4 16S rRNA sequence to determine the changes in the proportions of bacteria in the fecal samples of the dogs with inflammatory bowel disease (IBD) between before and after fecal microbiota transplantation (FMT) and to determine the proportions of bacteria in the fecal samples of the donor dogs. The phyla are shown in order from the top of the bar graph: other, Tenericutes, Proteobacteria, Fusobacteria, Firmicutes, Bacteroidetes, and Actinobacteria (Fig. 3A–C). The major bacterial phyla in the dogs with IBD were Firmicutes (51.7%), as shown in Fig. 3A, and Proteobacteria (80.3%, 52.2%), as shown in Fig. 3B and C. The proportions of Actinobacteria, Tenericutes, and Proteobacteria in the microbiome of donor dogs were low, and the major bacterial phyla were Bacteroidetes, Firmicutes, and Fusobacteria. Generally, the proportion of Fusobacteria decreased in the microbiome of dogs with IBD.

Fig. 4.

Results of real-time PCR performed to detect the proportion of Fusobacterium. The post-FMT proportion of Fusobacterium was significantly increased (p<0.05).