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

Abstract

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] μg/kg; P = .04) and day 63 (3.49 [0-28.43] μg/kg; P = .02) compared to day 0 (.14 [.03-1.19] μg/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.

In Vitro Evaluation of the Effects of Tylosin on the Composition and Metabolism of Canine Fecal Microbiota

“…Since Enterococcus spp. have been reported to develop resistance to TYL [9,10,57], an increase of these bacteria favored by this antibiotic would have been expected in the present study, according to previous trials in the dog, where the proliferation of this potentially probiotic bacterial group was interpreted as a consequence of a potential selective pressure exerted by TYL on the intestinal microbiota both in healthy [7,11] and pathological conditions [8]. The opposite results highlighted during the present study induce to suppose that the response of enterococci towards the presence of TYL might have been influenced by the specific "in vitro" conditions here set up.…”

“…Previous studies based on 16S rRNA sequencing techniques have reported marked changes both in jejunal [7] and fecal [11] microbiota of healthy dogs after TYL treatment, in particular, with a significant decrease in mean bacterial diversity and a reduction of the relative abundance of the most important bacterial taxa.…”

“…Nonetheless, a recent study investigating the effects of TYL on fecal microbiota of healthy dogs reported a decrease in microbial diversity indices and in the presence of commensal anaerobic bacteria such as Fusobacterium and Faecalibacterium spp. [11], generally considered to be beneficial in dogs and frequently depleted in canine gastrointestinal diseases [12].…”

Effect of amoxicillin‐clavulanic acid on clinical scores, intestinal microbiome, and amoxicillin‐resistant Escherichia coli in dogs with uncomplicated acute diarrhea

“…Recent investigations showed a profound effect of metronidazole and tylosin on the microbiota. Tylosin significantly increased the DI during treatment, and the abundance of Faecalibacterium was significantly decreased after treatment 46 . Also, treatment with metronidazole in dogs leads to significant alterations in the intestinal microbiome with decreased abundances of the taxa Bacteroidaceae , Clostridiaceae , Fusobacteriaceae , Lachnospiraceae , Ruminococcaceae , Turicibacteraceae , and Veillonellaceae and increased abundances of Bifidobacteriaceae , Enterobacteriaceae , Enterococcaceae , and Streptococcaceae 27 …”

Proposal for rational antibacterial use in the diagnosis and treatment of dogs with chronic diarrhoea

“…Very recently, as found in healthy dogs, it was shown that the administration of tylosin (20 mg/kg PO BID) induced dysbiosis-and eubiosis was not restored by 56 days following tylosin discontinuation, leading the authors to conclude that in these patients "… reestablishment of the native microbiota is possible but not guaranteed." (Manchester et al 2019). Faecal bacterial diversity was also reduced when administering oral metronidazole for 14 days (12.5 mg/kg BID) to healthy dogs (Igarashi et al 2014).…”