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PloS one2020; 15(5); e0232905; doi: 10.1371/journal.pone.0232905

The cecal and fecal microbiomes and metabolomes of horses before and after metronidazole administration.

Abstract: Antibiotic administration can be a cause of gastrointestinal disease in horses, creating a disruption in the normal population and function of bacteria found in the hindgut. The objective of this study was to describe the changes in the cecal and fecal microbiomes and metabolomes of clinically healthy horses before and after metronidazole administration. Metronidazole (15 mg/kg BID PO) was given to five horses with cecal cannulas. The study was suspended on Day 3 due to adverse gastrointestinal effects. Cecal and fecal samples were obtained before (Days minus52, m28, m14, and 0) and after (Days 7, 14, 28, and 52) metronidazole administration. DNA was extracted from the cecal and fecal samples, and 16S rRNA genes were sequenced. Richness and evenness indices were significantly decreased by metronidazole administration in both cecal and fecal samples, but the overall composition was only significantly changed in fecal samples on Day 3 (ANOSIM, p = 0.008). The most dominant phyla were Bacteroidetes and Firmicutes in all groups examined. In fecal samples, significant changes of the phyla Actinobacteria, Spirochaetes, Lentisphaerae, and Verrucomicrobia occurred on Day 3, which correlated with clinical signs of gastrointestinal disease. The metabolome was characterized by mass spectrometry-based methods and only named metabolites were included in the analysis. Fecal, but not cecal, metabolites were significantly affected by metronidazole. The fecal metabolites affected represent diverse metabolic pathways, such as the metabolism of amino acids, carbohydrates, lipids, nucleic acids and cofactors and vitamins. Metronidazole administration has potential to cause adverse effects in horses, alters the bacterial composition of the horse's cecal and fecal content, and the metabolome of fecal samples.
Publication Date: 2020-05-22 PubMed ID: 32442163PubMed Central: PMC7244109DOI: 10.1371/journal.pone.0232905Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explored the changes in horse’s hindgut bacteria and their function, before and after the administration of the antibiotic metronidazole. Due to the antibiotic’s adverse gastrointestinal effects, the project was halted on day 3.

Research Methodology

  • Five horses equipped with cecal cannulas, designed to collect samples from the cecum, were subjected to metronidazole administration at a dosage of 15mg/kg.
  • Cecal and fecal samples were gathered both before and after the metronidazole administration at various intervals: Days -52, -28, -14, 0, 7, 14, 28, and 52.
  • DNA was obtained and 16S rRNA genes were sequenced from the samples to identify the bacteria present.

Findings from the Study

  • Following the administration of metronidazole, there was a significant decrease in richness and evenness indices in both cecal and fecal samples. However, a significant change in overall composition was noted only in fecal samples on Day 3.
  • The most dominant phyla in all the groups studied were Bacteroidetes and Firmicutes.
  • In the fecal samples, major changes were noted on Day 3 in several phyla including Actinobacteria, Spirochaetes, Lentisphaerae, and Verrucomicrobia. These changes coincided with clinical signs of gastrointestinal disease in the horses.

Metabolomic Analysis

  • Metabolomic analysis was also carried out using mass spectrometry-based methods to identify the metabolites in the samples. Only named metabolites were included in the study.
  • Significant changes were observed in the fecal but not cecal metabolites after the administration of metronidazole.
  • The fecal metabolites affected were involved in a wide range of metabolic pathways such as the metabolism of amino acids, carbohydrates, lipids, nucleic acids, cofactors and vitamins.

Implications of the Study

  • The research showed that administering metronidazole had the potential to cause adverse gastrointestinal effects in horses and also triggered changes in the bacterial composition of the equine cecal and fecal content.
  • The study also revealed disruptions in the fecal metabolome, which may have functional implications affecting the horse’s health.

Cite This Article

APA
Arnold CE, Isaiah A, Pilla R, Lidbury J, Coverdale JS, Callaway TR, Lawhon SD, Steiner J, Suchodolski JS. (2020). The cecal and fecal microbiomes and metabolomes of horses before and after metronidazole administration. PLoS One, 15(5), e0232905. https://doi.org/10.1371/journal.pone.0232905

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 15
Issue: 5
Pages: e0232905

Researcher Affiliations

Arnold, Carolyn E
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Isaiah, Anitha
  • Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Pilla, Rachel
  • Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Lidbury, Jonathan
  • Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Coverdale, Josie S
  • Department of Animal Science, Texas A&M University, College Station, Texas, United States of America.
Callaway, Todd R
  • Department of Animal and Dairy Science, University of Georgia, Athens, Georgia, United States of America.
Lawhon, Sara D
  • Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Steiner, Joerg
  • Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Suchodolski, Jan S
  • Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Biodiversity
  • Cecum / drug effects
  • Cecum / metabolism
  • Cecum / microbiology
  • Feces / chemistry
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / genetics
  • Horses / metabolism
  • Horses / microbiology
  • Male
  • Metabolome / drug effects
  • Metronidazole / administration & dosage
  • RNA, Ribosomal, 16S

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 40 references