The cecal and fecal microbiomes and metabolomes of horses before and after metronidazole administration.
Authors: Arnold Carolyn E, Isaiah Anitha, Pilla Rachel, Lidbury Jonathan, Coverdale Josie S, Callaway Todd R, Lawhon Sara D, Steiner Joerg, Suchodolski Jan S
Journal: PloS one
Summary
# Editorial Summary: Metronidazole's Impact on Equine Hindgut Microbiota and Metabolism Metronidazole is commonly prescribed for horses with suspected anaerobic infections, yet little is known about its collateral effects on the broader microbial ecosystem of the hindgut. Arnold and colleagues investigated how this antibiotic alters both the bacterial community structure and metabolic output in the cecum and colon by administering metronidazole (15 mg/kg twice daily) to five healthy horses with cecal cannulas, though the study had to be discontinued on Day 3 due to gastrointestinal distress. Using 16S rRNA gene sequencing and mass spectrometry analysis, the researchers found that metronidazole rapidly depleted bacterial diversity in both cecal and fecal samples, with particularly dramatic compositional shifts in faecal microbiota by Day 3—notably reductions in Actinobacteria, Spirochaetes, Lentisphaerae, and Verrucomicrobia that directly correlated with the onset of clinical signs. The metabolomic changes were even more pronounced in faecal samples, affecting pathways central to amino acid, carbohydrate, lipid, and vitamin metabolism, whilst surprisingly sparing the metabolic profile in cecal contents. For practitioners, these findings underscore that metronidazole carries significant risks of iatrogenic dysbiosis and gastrointestinal dysfunction in horses, suggesting careful consideration of alternative therapies where possible and close monitoring for adverse effects if metronidazole use is deemed essential.
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Practical Takeaways
- •Metronidazole administration carries significant risk of gastrointestinal disruption and clinical disease in horses; use only when clearly indicated and monitor closely for adverse effects
- •Gastrointestinal signs appearing within 3 days of metronidazole initiation may reflect profound microbiome dysbiosis affecting multiple metabolic pathways; consider discontinuation
- •Fecal samples are more useful than cecal samples for monitoring metronidazole-induced microbiome changes in clinical practice
Key Findings
- •Metronidazole administration significantly decreased bacterial richness and evenness in both cecal and fecal samples within 3 days
- •Fecal microbiome composition changed significantly by Day 3, with decreased Actinobacteria, Spirochaetes, Lentisphaerae, and Verrucomicrobia correlating with clinical gastrointestinal signs
- •Metronidazole altered fecal metabolites across amino acid, carbohydrate, lipid, nucleic acid and vitamin metabolism pathways while cecal metabolites remained relatively unchanged
- •Study was terminated on Day 3 due to adverse gastrointestinal effects, suggesting metronidazole at 15 mg/kg BID poses risk in clinically healthy horses