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Veterinary medicine and science2025; 11(2); e70272; doi: 10.1002/vms3.70272

Investigation of the Blood Microbiome in Horses With Fever of Unknown Origin.

Abstract: Fever of unknown origin (FUO) without a respiratory component is a frequent clinical presentation in horses. Multiple pathogens, both tick-borne and enteric, can be involved as etiologic agents. An additional potential mechanism is intestinal barrier dysfunction. This case-control study aimed to detect and associate microbial taxa in blood with disease state. Areas known for a high prevalence of tick-borne diseases in humans were chosen to survey horses with FUO, which was defined as fever of 101.5°F or higher with no signs of respiratory illness or other recognisable diseases. Blood samples and clinical parameters were obtained from 52 FUO cases and also from matched controls from the same farms. An additional 23 febrile horses without matched controls were included. Broadly targeted polymerase chain reaction (PCR) amplification directed at conserved sequence regions of bacterial 16S rRNA, parasite 18S rRNA, coronavirus RdRp and parvovirus NS1 was performed, followed by deep sequencing. To control for contamination and identify taxa unique to the cases, metagenomic sequences from the controls were subtracted from those of the cases, and additional targeted molecular testing was performed. Sera were also tested for antibodies to equine coronavirus. Over 60% of cases had intestinal microbial DNA circulating in the blood. Nineteen percent of cases were attributed to infection with Anaplasma phagocytophilum, of which two were subtyped as human-associated strains. A novel Erythroparvovirus was detected in two cases and two controls. Serum titres for equine coronavirus were elevated in some cases but not statistically different overall between the cases and controls. Not all pathogens are expected to circulate in blood, which was the sole focus of this study. The presence of commensal gut microbes in blood of equine FUO cases is consistent with a compromised intestinal barrier, which is highlighted as a direction for future study.
© 2025 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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Publication Date: 2025-03-11 PubMed ID: 40065594PubMed Central: PMC11893731DOI: 10.1002/vms3.70272Google Scholar: Lookup
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  • Research Support
  • U.S. Gov't
  • P.H.S.
  • Research Support
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  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research is a case-control study that investigated the presence and relationship of microbial taxa in the blood of horses suffering from fever of unknown origin (FUO). The study findings suggest that FUO cases are often associated with intestinal microbial DNA in the blood, implying possible intestinal barrier dysfunction.

Objectives of the Study

  • The research aimed to detect and associate specific microbial taxa in the blood of horses with a disease (FUO) that exhibits no respiratory issues or other recognizable diseases.

Methods

  • The areas chosen for the investigation were known for a high prevalence of tick-borne diseases in humans.
  • They sampled blood and acquired clinical parameters from 52 FUO cases and matching controls from the same farms. An additional 23 febrile horses without matched controls were also included.
  • The methodology involved a broadly targeted polymerase chain reaction (PCR) amplification focussing on conserved sequence regions of bacterial 16S rRNA, parasite 18S rRNA, coronavirus RdRp, and parvovirus NS1. This was followed by deep sequencing.
  • To establish taxa unique to the cases and control contamination, they subtracted metagenomic sequences from the controls from those of the cases. Targeted molecular testing was also done.
  • Additionally, they tested horse sera for antibodies to equine coronavirus.

Results

  • Over 60% of FUO cases exhibited intestinal microbial DNA circulation in the blood, suggesting a possible dysfunctional intestinal barrier.
  • Nineteen percent of these cases were attributed to infection by Anaplasma phagocytophilum, with two subtyped as human-associated strains.
  • A novel Erythroparvovirus was detected in two cases and the matching controls.
  • The study found elevated serum titres for equine coronavirus in some cases, but there was no statistical difference overall between the cases and controls.

Conclusions

  • The study concluded that the presence of commensal gut microbes in the bloodstream of equine FUO cases could be indicative of a compromised intestinal barrier, warranting further studies on the role of the intestinal barrier in FUO in horses.
  • The research also concluded that not all pathogens linked to FUO would be expected to circulate in the blood.

Cite This Article

APA
Sun Y, Yu YT, Castillo XO, Anderson R, Wang M, Sun Q, Tallmadge R, Sams K, Reboul G, Zehr J, Brown J, Wang X, Marra N, Stanhope B, Grenier J, Pusterla N, Divers T, Mittel L, Goodman LB. (2025). Investigation of the Blood Microbiome in Horses With Fever of Unknown Origin. Vet Med Sci, 11(2), e70272. https://doi.org/10.1002/vms3.70272

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 11
Issue: 2
Pages: e70272

Researcher Affiliations

Sun, Yining
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Yu, Y Tina
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Castillo, Ximena Olarte
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Anderson, Renee
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Wang, Minghui
  • Center for Biotechnology, Cornell University, Ithaca, New York, USA.
Sun, Qi
  • Center for Biotechnology, Cornell University, Ithaca, New York, USA.
Tallmadge, Rebecca
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Sams, Kelly
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Reboul, Guillaume
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Zehr, Jordan
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Brown, Joel
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Wang, Xiyu
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Marra, Nicholas
  • Division of Science, Mathematics, and Technology, Governors State University, University Park, Illinois, USA.
Stanhope, Bryce
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Grenier, Jennifer
  • Center for Biotechnology, Cornell University, Ithaca, New York, USA.
Pusterla, Nicola
  • School of Veterinary Medicine, University of California, Davis, California, USA.
Divers, Thomas
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Mittel, Linda
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Goodman, Laura B
  • College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
  • School of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • Horses
  • Animals
  • Horse Diseases / microbiology
  • Horse Diseases / blood
  • Case-Control Studies
  • Fever of Unknown Origin / veterinary
  • Fever of Unknown Origin / microbiology
  • Fever of Unknown Origin / blood
  • Male
  • Female
  • Microbiota

Grant Funding

  • 1U18FD006993 / US Food and Drug Administration's Veterinary Laboratory Investigation and Response Network
  • U18 FD006716 / FDA HHS
  • W81XWH-22-1-0891 / Department of Defense
  • 1U18FD006716 / US Food and Drug Administration's Veterinary Laboratory Investigation and Response Network
  • U18 FD006993 / FDA HHS
  • Harry M. Zweig Memorial Fund for Equine Research

Conflict of Interest Statement

The authors declare no conflicts of interest.

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