Pigs as a Biomedical Model to StudyStress and Brain-Gut Axis Disorders

Adam Moeser, DVM PhDAssociate Professor

Matilda R. Wilson Endowed Chair Large Animal Clinical SciencesCollege of Veterinary Medicine

Intersection Between Animal and Human Health

Research Focus: Pathophysiology of Stress-Induced GI disorders

Early life adversity and Development of GI immune and

epithelial barrier functionBrain-Gut Axis

Stress is a Major Factor in the Onset and Exacerbation

of GI Disease in Animals and People

http://www.stress-management-for-health.com/physical-effects-of-stress.html

Irritable Bowel Syndrome (IBS)

Inflammatory Bowel Diseases (IBD)

GI Infections

Poor weight gain/feed conversion

Stress

Allergy

Weaning is a Stressful Early Life Event

Gastrointestinal disorders are a leading disease problem in weaned pigs

Pigs as a Biomedical Model for Stress and GI Disease

Complex brain/CNS and enteric nervous system

Intelligence Comparable size and

anatomy Comparable clinical GI

disease Similar ontogenic

development of the GI system

Similar dietary preference as omnivores

Comparable immune system

Intestinal Pathophysiology Associated with Pig Early Weaning Stress Model

Immediate and long-lasting disturbances in intestinal barrier function Smith et al 2012, American Journal of Physiology-GIL Moeser et al 2006, American Journal of Physiology-GIL Moeser et al 2008, American Journal of Physiology-GIL

Heightened responses to later life infectious challenges McLamb et al 2013, PloS One)

Chronic relapsing diarrhea and stress hypersensitivity Pohl et al, manuscript in preparation

Sex-specific, developmental alterations in EWS porcine model Medland et al 2016; under R1 review Neurogastroenterology and

Motility Pohl et al, manuscript in preparation

CRF receptor system regulation of Mast Cell degranulation and intestinal permeability Ayyadurai et al, manuscript in preparation D’Costa et al; manuscript in preparation

Early Life Stress Origins of Gastrointestinal Disease: Animal Models, Intestinal Pathophysiology, and

Translational Implications.

Invited Review: Early Life Stress Origins of Gastrointestinal Disease: Animal Models, Intestinal Pathophysiology, and Translational Implications.Pohl CS, Medland JE, Moeser AJ.American Journal of Physiology-GIL 2015 309:G927-41

• Saru Ayyadurai, Research Associate• Susan D’Costa, Research Associate• Laura Edwards RLATG• Shellsea Frandsen BS• Amelia Gibson PhD (KeraFast Inc.)• Liz Lennon, DVM DACVIM (U. Tenn)• Julia Medland MS (NCSU)• Emily Mackey, DVM/PhD student• Beth Overman, PhD (Methodist

University) • Calvin Pohl DVM, PhD student• Ashwin Poopal, MS• Laura Sommerville, Post Doc (Duke

University)• Yihang Li, Post Doc

Moeser Gastrointestinal Stress Biology Laboratory

Collaborators for this research• Soman Abraham PhD, Duke

University• Jean Rivier PhD, The Salk Institute,

La Jolla, CA • Richard Neubig MD PhD, MSU

Pharm Tox• Jim Galligan PhD, MSU Pharm Tox,

Neuroscience Program• Tony Pease DVM DACVR, MSU CVM

Radiology

Lab Funding • American

Gastroenterological Association (AGA)

• National Institutes of Health grants

– NIH R01 HD072968– NIH R03 DK097462– NIH K08 DK097462

• National Pork Board

• NC Pork Council• USDA• UNC Chapel Hill

Center for Gastrointestinal Biology and Disease

Acknowledgements