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Pigs as a Biomedical Model to Study
Stress and Brain-Gut Axis Disorders
Adam Moeser, DVM PhD
Associate Professor
Matilda R. Wilson Endowed Chair
Large Animal Clinical Sciences
College 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 function
Brain-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
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

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Pigs as a Biomedical Model for Stress and Brain-Gut Axis Disorders

  • 1. Pigs as a Biomedical Model to Study Stress and Brain-Gut Axis Disorders Adam Moeser, DVM PhD Associate Professor Matilda R. Wilson Endowed Chair Large Animal Clinical Sciences College of Veterinary Medicine
  • 2. Intersection Between Animal and Human Health
  • 3. Research Focus: Pathophysiology of Stress-Induced GI disorders Early life adversity and Development of GI immune and epithelial barrier function Brain-Gut Axis
  • 4. 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 Allergy
  • 5. Weaning is a Stressful Early Life Event Gastrointestinal disorders are a leading disease problem in weaned pigs
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. • 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

Hinweis der Redaktion

  1. The current research focus in my laboratory is on the elucidating the mechanisms by which stress impacts GI gut defense mechanisms predisposing individuals to GI disorders Two main focus areas in my laboratory are the impact of ELS on GI Immune and epithelial barrier development and how this can influence lifetime GI disease susceptibility. The other focus area is connected and is focused on regulation of mast cell activation by stress which is an effector immune cell in the stress response