Multimodal investigation of molecular mechanisms underlying gastrointestinal health and disease in horses

Colic (abdominal pain) related to gastrointestinal disease is a major health and welfare concern for horses worldwide. Despite the common occurrence and potentially severe consequences of colic, there remains much room for improvement in both diagnosis and treatment outcomes for equine colic patients. The overarching aim of the work presented here was to add to our understanding of the etiology and pathophysiology of equine colic by probing underlying mechanisms of gastrointestinal homeostasis and disease in horses. This was achieved through three specific aims: 1) describe and compare microbial populations in equine gastric fluid and feces and evaluate stability of those populations over time; 2) validate and assess clinical utility of commercial assays for quantification of inflammatory biomarkers in equine feces; and 3) quantify alterations in the peritoneal fluid proteome of horses with colic. Aim 1: Understanding the composition and stability of gastric fluid microbiota in healthy horses is a prerequisite to understanding changes associated with the development of disease. We found that there was decreased richness and diversity of microbiota in gastric fluid compared to feces and that there was a consistent subpopulation of gastric microbiota across individuals and over time. These findings provide a basis for further investigation of gastric fluid microbiota in diseases of the foregut. Aim 2: Intestinal inflammation is challenging to diagnose in horses; fecal inflammatory biomarkers are a direct product of intestinal inflammation, and could provide valuable information for assisting in the diagnosis of inflammatory conditions of the intestine in horses. Assays for two biomarkers, calprotectin (CP) and myeloperoxidase (MPO), were systematically evaluated, with findings supporting quantification of fecal CP by ELISA, but not MPO. In a follow-up study, a reference interval for fecal CP in healthy horses was described, and preliminary clinical evaluation found that fecal CP was increased in horses with colitis. Aim 3: Peritoneal fluid (PF) is intimately associated with the gastrointestinal tract and thus is a useful source of information to aid in diagnosis and prognostication. Individual PF biomarkers do not adequately predict outcomes in horses with colic, but a proteomics approach may provide a more wholistic picture of the peritoneal environment. Liquid chromatography-tandem mass spectroscopy-based unbiased proteomic analysis of PF from horses with colic identified unique and differentially abundant proteins related to ischemic intestinal lesions (as compared to non-ischemic), with functional enrichments related to inflammatory and immune responses. Several proteins, including calprotectin, lactotransferrin, alpha 2 macroglobulin, and apolipoprotein B were identified as candidates of interest for further study. Together, the outcomes of these three aims provide the basis for future mechanistic studies with an eye towards development of clinical applications. Next steps include investigation of gastric microbiota in horses with colic, evaluation of fecal CP in a larger group of horses with inflammatory conditions of the intestine, and correlation of proteomics findings with transcriptomic and metabolomic data.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

VMS - Comparative Biosciences

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Bishop, Rebecca Coco

Contributors dc:contributor

• McCoy, Annette M
• Wilkins, Pamela A
• Mei, Wenyan
• Wang, Bo

• colic
• colitis
• horse
• intestinal disease
• peritoneal fluid
• biomarker
• proteomics
• microbiome
• gastric fluid
• inflammation

Statement dc:rights

• Copyright 2025 Rebecca Coco Bishop

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129668

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129668