A systems biology approach to investigating host-microbiome interactions and their implications for gastrointestinal health in dogs and cats

Barko, Patrick

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https://hdl.handle.net/2142/124527 Copy

Description

Title

A systems biology approach to investigating host-microbiome interactions and their implications for gastrointestinal health in dogs and cats

Author(s)

Barko, Patrick

Issue Date

2024-04-19

Director of Research (if dissertation) or Advisor (if thesis)

Williams, David A

Doctoral Committee Chair(s)

Williams, David A

Committee Member(s)

• Miller, Gay
• Maddox, Carol
• Swanson, Kelly
• Reinhart, Jennifer
• Gal, Arnon
• Czarnecki-Maulden, Gail

Department of Study

Pathobiology

Discipline

VMS - Pathobiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Chronic Enteropathy
• Veterinary Medicine
• Gastroenterology
• Microbiome
• Metabolome

Language

eng

Abstract

The intestinal tract is a unique organ system in that it is the largest epithelial surface in contact with the external environment. It must maintain a selective permeability to dietary nutrients, protect the underlying tissues from the potentially pathogenic effects of luminal microbiota, and mediate health-promoting signals provided by beneficial commensal microbiota. Thus, host-microbiome interactions are critical for regulating intestinal mucosal homeostasis due to their impacts on nutrient digestion and absorption, mucosal barrier function, and inflammatory responses. The effects of enteric microbiota on intestinal homeostasis are largely mediated by host tissue responses to microbial antigens (e.g., lipopolysaccharide) and products of microbial metabolism (e.g., short-chain fatty acids, secondary bile acids, and amino acid catabolites). Enteric microbiota dysbiosis (EMD) is characterized by decreased microbiota diversity, decreased abundance of commensal organisms that support homeostasis, and increased abundance of potential pathobionts. EMD has the potential to disrupt intestinal mucosal homeostasis by inducing mucosal inflammatory responses and disrupting the integrity of the mucosal barrier. Many previous investigations have implicated EMD in the pathogenesis and pathophysiology of chronic enteropathies and exocrine pancreatic disorders in humans, dogs, and cats. Despite growing recognition of the importance of enteric microbiota in various disease states, mechanisms of host-microbiome interactions are poorly understood in dogs and cats. Herein, the clinical and pathophysiologic significance of EMD in disorders associated with chronic intestinal dysfunction in dogs and cats were investigated using a systems biology approach. Chapters 1 and 2 revealed evidence of persistent EMD in dogs with exocrine pancreatic insufficiency that, in some dogs, was associated with disturbances in bile acid metabolism and altered regulation of mucosal barrier function. In Chapter 3, fecal concentrations of cathelicidin-related antimicrobial peptide (CRAMP) were found to be decreased in dogs with EPI, suggesting it may play a role in the pathogenesis and persistence of EMD. Investigations in Chapters 4 and 5 revealed disturbances in microbial indole catabolite of tryptophan (MICT) in cats with chronic enteropathies (CE). These changes in MICTS were associated with EMD characterized by profoundly decreased abundances of fecal Bifidobacterium spp. Finally, in Chapter 6, mechanisms through which MICTs regulate mucosal barrier function and inflammation were investigated using canine colonic epithelial cell cultures exposed to TNF. MICTs were shown to ameliorate mucosal barrier dysfunction and pro-inflammatory responses in this in vitro model. The investigations described in this thesis provide new insights regarding the roles of EMD in spontaneous enteropathies commonly diagnosed in dogs and cats. These observations open new avenues to investigate novel diagnostic and therapeutic approaches to these important digestive diseases of companion animals.

Graduation Semester

2024-05

Type of Resource

Text

Handle URL

https://hdl.handle.net/2142/124527

Copyright and License Information

Copyright 2024 Patrick Barko

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