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Communications biology2025; 8(1); 1711; doi: 10.1038/s42003-025-09111-7

Bile acids segregate metabolic syndrome in a cohort of 100 deeply phenotyped horses.

Abstract: Metabolic syndrome (MetS)-encompassing obesity, insulin resistance, dyslipidemia, and hypertension-is prevalent in both humans and horses, offering a unique opportunity to explore shared pathophysiological mechanisms across species in a controlled model organism. In this first report from the Pioneer 100 Horse Health Project (P100HHP), we conducted a longitudinal, multi-omic analysis of 108 deeply phenotyped horses to interrogate individual health trajectories for precision insights into MetS. We identified two primary metabotypes: one characterized by elevated unsaturated triglycerides (TGs) and the other by increased levels of primary bile acids (BAs), notably taurocholic acid and taurochenodeoxycholic acid. Horses with higher circulating levels of taurocholic acid had significantly higher plasma insulin concentrations, especially after an oral sugar challenge (P = 0.01), indicating that specific BAs are associated with hyperinsulinemia-a key phenotype of MetS. Metabolomic signatures predicted body condition score (relative adiposity) with high performance, underscoring their potential for precision diagnostics. Seasonal variations influenced BA levels and were associated with shifts in the fecal microbiota, particularly in Clostridium and Proteobacteria populations. Additionally, we observed an inverse relationship between genetic diversity-measured by runs of homozygosity-and insulin levels, suggesting a genetic component to MetS susceptibility. Our findings demonstrate the power of deep phenotyping and multi-omic approaches to effectively delineate MetS subtypes in horses, highlighting the pivotal roles of bile acids and the microbiome in MetS pathogenesis. These insights not only advance the understanding of equine MetS but also establish the horse as a valuable translational model for human MetS, with potential implications for targeted diagnostics and therapeutics in both veterinary and human medicine.
© 2025. The Author(s).
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Publication Date: 2025-11-27 PubMed ID: 41310118PubMed Central: PMC12660777DOI: 10.1038/s42003-025-09111-7Google Scholar: Lookup
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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.

Overview

  • This study analyzed metabolic syndrome (MetS) in a well-characterized population of 108 horses to identify different metabolic profiles and their relation to disease features such as insulin resistance and obesity.
  • It highlighted the role of bile acids and gut microbiota in MetS and proposed horses as a useful model for understanding and diagnosing MetS in both animals and humans.

Study Context and Objectives

  • Metabolic syndrome (MetS) includes a cluster of conditions: obesity, insulin resistance, dyslipidemia, and hypertension.
  • MetS is common in both humans and horses, making horses a valuable controlled model to explore shared biological mechanisms across species.
  • The Pioneer 100 Horse Health Project (P100HHP) aimed to deeply phenotype 108 horses longitudinally, collecting multi-omic data to understand individual variations in health and MetS progression.

Key Findings and Metabotypes Identified

  • Two primary metabolic profiles (metabotypes) were discovered among the horses:
    • One group showed elevated levels of unsaturated triglycerides (TGs).
    • The other group exhibited increased levels of primary bile acids (BAs), specifically taurocholic acid and taurochenodeoxycholic acid.
  • Horses with higher circulating taurocholic acid levels exhibited significantly higher plasma insulin concentrations, particularly after an oral sugar challenge, linking these bile acids to hyperinsulinemia, a hallmark of MetS.

Diagnostic and Predictive Potential

  • Metabolomic signatures correlated strongly with body condition score (a measure of relative adiposity), suggesting metabolites could serve as precise diagnostic tools for MetS.

Influence of Season and Microbiome

  • Seasonal changes affected bile acid levels in the horses.
  • These variations were associated with shifts in gut microbial populations, especially bacteria from the Clostridium and Proteobacteria groups.
  • The findings emphasize the interaction between bile acids and the gut microbiome as an important factor in MetS development.

Genetics and MetS Susceptibility

  • An inverse relationship was found between genetic diversity (measured by runs of homozygosity) and insulin levels.
  • This suggests a genetic predisposition to MetS, where lower genetic diversity may increase susceptibility to insulin dysregulation.

Implications and Significance

  • The study demonstrates that deep phenotyping combined with multi-omic analyses can effectively stratify MetS subtypes in horses, enabling precision insights.
  • It identifies bile acids and the microbiome as key players in MetS pathogenesis.
  • By establishing horses as a translational model, the research opens opportunities for developing targeted diagnostics and treatments applicable to veterinary and human metabolic disorders.

Cite This Article

APA
Donnelly CG, Peng S, Pflieger L, Manfredi J, Coleman M, Rappaport N, Price ND, Finno CJ. (2025). Bile acids segregate metabolic syndrome in a cohort of 100 deeply phenotyped horses. Commun Biol, 8(1), 1711. https://doi.org/10.1038/s42003-025-09111-7

Publication

Communications biology
ISSN: 2399-3642
NlmUniqueID: 101719179
Country: England
Language: English
Volume: 8
Issue: 1
Pages: 1711
PII: 1711

Researcher Affiliations

Donnelly, Callum G
  • College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. cgd43@cornell.edu.
Peng, Sichong
  • EclipseBio, San Diego, CA, USA.
Pflieger, Lance
  • Phenome Health, Seattle, WA, USA.
Manfredi, Jane
  • College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Coleman, Michele
  • College of Veterinary Medicine, Georgia State University, Athens, GA, USA.
Rappaport, Noa
  • Phenome Health, Seattle, WA, USA.
  • Institue of Systems Biology, Seattle, WA, USA.
Price, Nathan D
  • Buck Institute for Research on Aging, Novato, CA, USA.
  • Thorne, New York, NY, USA.
Finno, Carrie J
  • School of Veterinary Medicine, University of California, Davis, CA, USA.

MeSH Terms

  • Animals
  • Metabolic Syndrome / veterinary
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / metabolism
  • Horses
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / blood
  • Horse Diseases / blood
  • Horse Diseases / metabolism
  • Phenotype
  • Male
  • Female

Grant Funding

  • D21EQ-050 / Morris Animal Foundation (MAF)

Conflict of Interest Statement

Competing interests: The authors declare no competing interests.

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