Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

Abstract

The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.

Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs

“…Indeed, a clinical trial in dogs with acute diarrhea receiving metronidazole treatment for 7 days demonstrated that their microbiome was still dysbiotic after 28 days. 13 Similar results have been reported in healthy dogs receiving tylosin for 7 days. 16 During the 2 weeks of metronidazole administration, 9 of the 16 dogs developed diarrhea, as reported by their owners.…”

“…Therapeutic modulation of the microbiota is therefore a desirable approach in animals with gastrointestinal disease. 12,13 Antimicrobials are used empirically for treatment of both acute and chronic gastrointestinal disease. Antimicrobials, however, can disrupt the intestinal microbiome for a prolonged period of time.…”

Developmental stages in microbiota, bile acids, and clostridial species in healthy puppies

“…22 Conversely, Clostridium hiranonis has 7α-dehydroxylation activity, 23 is part of the DI of dogs, 12 and is likely the main contributor to the secondary bile acid pool in dogs. 6,24 Therefore, the association between the development of bile acid profiles and the development of the microbiota, and the potential influence of bile acids on Clostridial species in growing puppies needs further examination.…”

Cholestyramine treatment in two dogs with presumptive bile acid diarrhoea: a case report

“…Numerous treatment protocols, including additional immunosuppressive treatments such as cyclosporine and mycophenolate mofetil, metronidazole and dietary changes were tried at different times during this period (Table 3 ). A faecal microbiota transplantation was given once as a rectal enema at a dose of 5 g of frozen donor stool per kg body weight as described by Chaitman and co-workers [ 10 ]. The stool was thawed and blended with 0.9% saline on the day of administration.…”