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

Jennifer Chaitman,Jonathan A Lidbury,Rachel Pilla,Anna-Lena Ziese,Stefan Unterer,Jörg M Steiner,Blake C Guard,Anitha Isaiah,Amanda B Blake,Jan S Suchodolski,Yasushi Minamoto

doi:10.3389/fvets.2020.00192

Jennifer Chaitman, Jonathan A Lidbury + Show 9 more

Open Access

https://doi.org/10.3389/fvets.2020.00192

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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.

Highlights

Acute diarrhea (AD) is a common presenting complaint in dogs in everyday primary veterinary practice
Dogs with acute uncomplicated diarrhea showed significant alterations in the fecal microbiota, and significant alterations in the fecal metabolome compared to healthy dogs
These results are consistent with previous studies evaluating the microbiota in dogs with acute diarrhea

Summary

Introduction

Acute diarrhea (AD) is a common presenting complaint in dogs in everyday primary veterinary practice. Surveys showed that 50–71% of dogs with AD presented to a veterinarian were treated with antimicrobials [1,2,3], only a minority (3.2%) of these animals were tested for infectious agents [3]. Studies have shown that antibiotics alter the gut microbiota, leading to lower microbial diversity, changes in specific bacterial taxa abundance and metabolic shifts [6,7,8]. In humans and companion animals, antibiotic use is associated with development of diarrhea in a subset of patients [7, 9]. Intestinal dysbiosis associated with antibiotic use, especially during early life stages, has been associated with increased risk for inflammatory bowel disease [10], as well as atopy [11], or obesity [12] in humans

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