Exploration of the Fecal Microbiota and Biomarker Discovery in Equine Grass Sickness.
Abstract: Equine grass sickness (EGS) is a frequently fatal disease of horses, responsible for the death of 1 to 2% of the U.K. horse population annually. The etiology of this disease is currently uncharacterized, although there is evidence it is associated with Clostridium botulinum neurotoxin in the gut. Prevention is currently not possible, and ileal biopsy diagnosis is invasive. The aim of this study was to characterize the fecal microbiota and biofluid metabolic profiles of EGS horses, to further understand the mechanisms underlying this disease, and to identify metabolic biomarkers to aid in diagnosis. Urine, plasma, and feces were collected from horses with EGS, matched controls, and hospital controls. Sequencing the16S rRNA gene of the fecal bacterial population of the study horses found a severe dysbiosis in EGS horses, with an increase in Bacteroidetes and a decrease in Firmicutes bacteria. Metabolic profiling by H nuclear magnetic resonance spectroscopy found EGS to be associated with the lower urinary excretion of hippurate and 4-cresyl sulfate and higher excretion of O-acetyl carnitine and trimethylamine-N-oxide. The predictive ability of the complete urinary metabolic signature and using the four discriminatory urinary metabolites to classify horses by disease status was assessed using a second (test) set of horses. The urinary metabolome and a combination of the four candidate biomarkers showed promise in aiding the identification of horses with EGS. Characterization of the metabolic shifts associated with EGS offers the potential of a noninvasive test to aid premortem diagnosis.
Publication Date: 2018-02-02 PubMed ID: 29364680DOI: 10.1021/acs.jproteome.7b00784Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the fecal microbiota and biofluid metabolic profiles of horses with Equine Grass Sickness (EGS), a disease leading to the death of 1-2% of the UK horse population annually. The goal of the study was to better understand EGS and to identify potential metabolic biomarkers that could assist in its diagnosis.
Introduction and Goals of the Research
- The authors of this study aimed to investigate Equine Grass Sickness (EGS), a disease whose cause remains unconfirmed but is suspected to be associated with the presence of Clostridium botulinum neurotoxin in the horse’s digestive tract.
- Due to the current inability to adequately prevent or noninvasively diagnose EGS, the researchers sought to gain a deeper understanding of the disease’s underlying mechanisms.
- This was done by characterizing the fecal microbiota and biofluid metabolic profiles of horses that suffer from EGS. This characterization could then aid in the identification of metabolic biomarkers for the disease.
Research Methods and Findings
- The study involved collection and analysis of urine, plasma, and feces from a selection of EGS-stricken horses, healthy controls, and hospital controls.
- The researchers sequenced the 16S rRNA gene of the fecal bacterial population of the study horses. This gene sequencing revealed that horses with EGS had a significant imbalance or dysbiosis of gut bacteria, characterized by increased levels of Bacteroidetes and decreased levels of Firmicutes bacteria.
- A metabolic profiling was carried out using hydrogen nuclear magnetic resonance spectroscopy. This revealed that EGS was associated with lower urinary excretion of hippurate and 4-cresyl sulfate, and higher excretion of O-acetyl carnitine and trimethylamine-N-oxide.
Evaluation of Findings and Potential Impact
- The researchers evaluated the predictive ability of the complete urinary metabolic signature and the four discriminatory urinary metabolites by classifying a second set of horses based on their disease status.
- Both the urinary metabolome of the horses and the combination of the four identified biomarkers showed potential in assisting the identification of horses with EGS.
- The discovery and characterization of metabolic shifts associated with EGS potentially paves the way for the development of a noninvasive test to assist with diagnosing EGS before death occurs, consequently improving disease management.
Cite This Article
APA
Leng J, Proudman C, Darby A, Blow F, Townsend N, Miller A, Swann J.
(2018).
Exploration of the Fecal Microbiota and Biomarker Discovery in Equine Grass Sickness.
J Proteome Res, 17(3), 1120-1128.
https://doi.org/10.1021/acs.jproteome.7b00784 Publication
Researcher Affiliations
- School of Veterinary Medicine, Vet School Main Building, Daphne Jackson Road, University of Surrey , Guildford, Surrey GU2 7AL, United Kingdom.
- School of Veterinary Medicine, Vet School Main Building, Daphne Jackson Road, University of Surrey , Guildford, Surrey GU2 7AL, United Kingdom.
- School of Biological Sciences, University of Liverpool , Crown Street, Liverpool L69 7ZB, United Kingdom.
- School of Biological Sciences, University of Liverpool , Crown Street, Liverpool L69 7ZB, United Kingdom.
- Philip Leverhulme Equine Hospital, University of Liverpool , Leahurst Campus, Chester High Road, Wirral CH64 7TE, United Kingdom.
- Philip Leverhulme Equine Hospital, University of Liverpool , Leahurst Campus, Chester High Road, Wirral CH64 7TE, United Kingdom.
- Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , London SW7 2AZ, United Kingdom.
MeSH Terms
- Acetylcarnitine / blood
- Acetylcarnitine / urine
- Animals
- Bacteroidetes / classification
- Bacteroidetes / isolation & purification
- Biomarkers / blood
- Biomarkers / urine
- Clostridium botulinum / metabolism
- Clostridium botulinum / pathogenicity
- Cresols / blood
- Cresols / urine
- Dysbiosis / blood
- Dysbiosis / diagnosis
- Dysbiosis / microbiology
- Dysbiosis / urine
- Feces / microbiology
- Firmicutes / classification
- Firmicutes / isolation & purification
- Gastrointestinal Microbiome
- Hippurates / blood
- Hippurates / urine
- Horse Diseases / blood
- Horse Diseases / diagnosis
- Horse Diseases / microbiology
- Horse Diseases / urine
- Horses
- Magnetic Resonance Spectroscopy
- Methylamines / blood
- Methylamines / urine
- RNA, Ribosomal, 16S / genetics
- Sulfuric Acid Esters / blood
- Sulfuric Acid Esters / urine
Citations
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