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Early weaning stress induces chronic functional diarrhea, intestinal barrier defects, and increased mast cell activity in a porcine model of early life adversity
Abstract
Background: Early life adversity ( ELA ) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood. Methods: Utilizing a porcine early weaning stress ( EWS ) model to mimic ELA , we investigated the long‐term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia. Key Results: Juvenile and adult EWS pigs exhibited chronic, functional diarrhea ( EWS 43.6% vs late wean control( LWC ) 4.8%, P <.0001), increased intestinal permeability (2 fold increase EWS vs LWC , P <.0001), and mast cell numbers (at 7 weeks and 20 weeks ~1.6 fold increase EWS vs LWC , P <.05). Compared with EWS male castrates (Male‐C), females EWS pigs exhibited more frequent diarrhea (58.8% vs 29.9%, P =.0016), and increased intestinal permeability (1‐2 fold higher in EWS females, P <.001). Increased mast cell numbers and their enhanced co‐localization with neuronal ganglia were observed in both Male‐C and female EWS pigs; however, female pigs exhibited greater release of mast cell tryptase upon activation with c48/80 (~1.5 fold increase, P <.05), compared with Male‐C pigs. Conclusions and Inferences: These data demonstrate that pigs exposed to ELA exhibit increased vulnerability to functional diarrhea, intestinal permeability and mast cell activity. Further, these studies also showed that EWS female and Male‐C pigs exhibited dimorphic responses to EWS with female piglets exhibited greater susceptibility and severity of diarrhea, intestinal permeability and mast cell tryptase release. Together, these findings mimic some of the key pathophysiologic findings in human functional GI disorders functional gastrointestinal disorders ( FGID s) suggesting that the EWS porcine model could be a valuable preclinical translational model for FGID research associated with ELA .
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“The combination of maternal separation and early weaning induces symptoms of IBS in pigs, and these correlate with increased numbers and activation of intestinal mast cells. 203”
From Mast cell ontogeny: From fetal development to life‐long health and disease (2023) · cites this paper as [203]
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Sorted by citations
Moeser, A. J., Pohl, C. S., & Rajput, M. (2017) · Animal nutrition · doi:10.1016/j.aninu.2017.06.003 · Cited by 452
“Similar to human IBS, Pohl et al. (2017) demonstrated that adult pigs that were previously early weaned (16 d wean age) exhibited enhanced co-localization of intestinal mast cells with enteric nerves, compared with late weaned pigs (weaned at 28 d of age) (Pohl et al., 2017).”
BackgroundResultInfluentialMast cell ontogeny: From fetal development to life‐long health and disease
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Ziegler, A. L., & Blikslager, A. T. (2017) · Neurogastroenterology & Motility · doi:10.1111/nmo.13216 · Cited by 9
Metadata
- Authors
- Pohl, C. S., Medland, J. E., Mackey, E., Edwards, L. L., Bagley, K. D., DeWilde, M. P., Williams, K. J., & Moeser, A. J.
- Affiliations
- Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing MI USA
- Department of Population Health and Pathobiology College of Veterinary Medicine North Carolina State University Raleigh NC USA
- Department of Pathobiology and Diagnostic Investigation College of Veterinary Medicine Michigan State University East Lansing MI USA
- ORCID
- Moeser, A. J.
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2017-06
- Volume
- 29
- Issue
- 11
- ISSN
- 1350-1925
- 1365-2982
- PMC
- PMC5650513
- Cited by
- 100
- References
- 14
- Language
- en
- Funders
- National Institutes of Health (HD072968, DK097462, R03 DK097462, OD011070)
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