Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs

Background Tylosin is commonly prescribed to dogs with diarrhea. Orally administered antibiotics may alter the intestinal microbiota, which is responsible for crucial key bile acid (BA) biotransformation reactions. Objectives To prospectively evaluate the impact of tylosin administration on fecal microbiota and unconjugated bile acids (UBAs) over time. Animals Sixteen healthy adult dogs. Methods Prospective, randomized controlled clinical trial. Dogs were randomized to receive 20 mg/kg of tylosin or a placebo capsule PO q12h for 7 days while undergoing daily fecal scoring. Fecal samples were collected on days 0, 7, 21, and 63. The microbiota was assessed using quantitative PCR and 16S rRNA gene sequencing. Unconjugated BAs were assessed using gas chromatography-mass spectrometry (GC-MS). Results Fecal scores were unchanged during placebo and tylosin administration. In the placebo group, no significant changes were observed in fecal microbiota or UBA concentrations. Day 7 samples from tylosin-exposed dogs exhibited decreased bacterial diversity (observed species, Chao1, Shannon, P < .001) characterized by decreases in anaerobes Fusobacteriaceae (linear discriminant analysis [LDA] score, 5.03) and Veillonellaceae (LDA score, 4.85). Primary UBA concentrations were increased at day 21 (median, [range]; 7.42, [0.67-18.77] mu g/kg; P = .04) and day 63 (3.49 [0-28.43] mu g/kg; P = .02) compared to day 0 (.14 [.03-1.19] mu g/kg) in dogs receiving tylosin. At day 63, bacterial taxa were not significantly different compared to day 0, but the extent of microbial recovery was individualized. Conclusions and Clinical Importance Tylosin causes fecal dysbiosis in healthy dogs with corresponding shifts in fecal UBAs. Changes did not uniformly resolve after discontinuation of tylosin.