Longitudinal effects of oral administration of antimicrobial drugs on fecal microbiota of horses

Abstract

BACKGROUND: Antimicrobial drug-associated diarrhea (AAD) is the most common adverse effect in horses receiving antimicrobials. Little information on how oral administration of antimicrobials alters intestinal microbiota in horses is available. OBJECTIVE: Investigate changes of the fecal microbiota in response to oral administration of antimicrobials. ANIMALS: Twenty healthy horses. METHODS: Prospective, longitudinal study. Horses were randomly assigned to 4 groups comprising 4 horses each: group 1 (metronidazole); group 2 (erythromycin); group 3 (doxycycline); group 4 (sulfadiazine/trimethoprim, SMZ-TMP); and group 5 (control). Antimicrobials were administered for 5 days. Fecal samples were obtained before (day 0) and at 1, 2, 3, 4, 5, 6, and 30 days of the study period. Fecal microbiota was characterized by high throughput sequencing of the V4 region of the 16S rRNA. RESULTS: Horses remained healthy throughout the study. Richness and diversity in doxycycline, erythromycin, and metronidazole, but not SMZ-TMP groups, was significantly lower (P < .05) at multiple time points after administration of antimicrobials compared with samples from day 0. Main changes in the microbiota were observed during the time of antimicrobial administration (day 2-5; weighted and unweighted UniFrac PERMANOVA P < .05). Administration of erythromycin, doxycycline and, to a lesser extent, metronidazole produced a pronounced alteration in the microbiota compared with day 0 samples by decreasing the abundance of Treponema, Fibrobacter, and Lachnospiraceae and increasing Fusobacterium and Escherichia-Shigella. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral administration of antimicrobials alters the intestinal microbiota of healthy horses resembling horses with dysbiosis, potentially resulting in intestinal inflammation and predisposition to diarrhea.