Alterations in the Fecal Microbiome and Metabolome of Horses with Antimicrobial-Associated Diarrhea Compared to Antibiotic-Treated and Non-Treated Healthy Case Controls.

Carolyn Arnold,Keith Chaffin,Jonathan Lidbury,Rachel Pilla,Joerg Steiner,Jan Suchodolski

doi:10.3390/ani11061807

Carolyn Arnold, Keith Chaffin + Show 4 more

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https://doi.org/10.3390/ani11061807

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Abstract

Simple SummaryAntimicrobials reduced the diversity and altered the bacterial community composition of the fecal microbiome of horses. Horses that develop antimicrobial-associated diarrhea (AAD) show greater derangements in their bacterial community composition compared to antibiotic (ABX) and non-antibiotic (CON) control horses. Horses with AAD have altered metabolic profiles compared to ABX and CON horses.Diarrhea is an adverse effect of antimicrobial therapy in horses. This matched, case-controlled study compared the fecal microbiome and metabolome of horses on antibiotics that developed diarrhea (AAD, n = 17) to those that did not develop diarrhea (ABX, n = 15) and to a control population not exposed to antibiotics (CON, n = 31). Fecal samples were collected from horses that were matched for diet and antimicrobial agent (including dose, route, and duration of therapy). Illumina sequencing of 16S rRNA genes was performed, and QIIME 2.0 was used to generate alpha and beta diversity metrics. Untargeted metabolomics using GC-MS platforms was performed and analyzed using Metaboanalyst 5.0. Microbiome composition was significantly different in AAD compared to CON (ANOSIM, R = 0.568, p = 0.001) but not to ABX (ANOSIM, R = 0.121, p = 0.0012). AAD and ABX horses had significantly decreased richness and evenness compared to CON horses (p < 0.05). Horses on antimicrobials (AAD and ABX) had significant changes in 14 phyla compared to CON horses. Only Verrucomicrobia distinguished AAD from ABX and CON horses (q = 0.0005). Metabolite profiles of horses with AAD clustered separately from ABX and CON horses. Seven metabolites were found to be significantly different between groups (p < 0.05): L-tyrosine, kynurenic acid, xanthurenic acid, 5-hydroxyindole-3-acetic acid, docosahexaenoic acid ethyl ester, daidzein, and N-acetyltyramine. Metabolite profiles of horses on antimicrobials, especially those with AAD, are altered compared to CON horses.

Highlights

Antimicrobial-associated diarrhea (ADD) is a common adverse effect of antibiotic use in horses [1]
One retrospective study found that horses with associated diarrhea (AAD) were 4.5 times more likely to die compared to horses with other types of colitis [17]
AAD and ABX horses were matched by the specific antimicrobial and the duration of antibiotic therapy on which diarrhea developed in the AAD horse

Summary

Introduction

Antimicrobial-associated diarrhea (ADD) is a common adverse effect of antibiotic use in horses [1]. AAD has been reported to range from 22 to 94% in adult horses with mortality rates ranging from 15 to 50% [4,5,8]. One retrospective study found that horses with AAD were 4.5 times more likely to die compared to horses with other types of colitis [17]. These factors indicate an urgent need to better understand why AAD develops, to identify individuals at risk, and to improve the morbidity and survival rates of horses with this disease

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