Hypoxia exacerbates heat stress effects on the porcine intestinal epithelium in vitro

Authors: Pearce, Sarah; GABLER, NICHOLAS - Iowa State University

Submitted to: Frontiers in Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2023
Publication Date: 7/18/2023
Citation: Pearce, S.C., Gabler, N.K. 2023. Hypoxia exacerbates heat stress effects on the porcine intestinal epithelium in vitro. Frontiers in Animal Science . 4. https://doi.org/10.3389/fanim.2023.1204152.
DOI: https://doi.org/10.3389/fanim.2023.1204152

Interpretive Summary: High environmental temperatures (heat stress) in animals cause gastrointestinal damage in livestock species. Heat stress affects multiple organs in the body, but the gastrointestinal tract is particularly sensitive to elevated temperatures. Part of the reason gastrointestinal damage occurs is thought to be due to blood redistribution from internal organs to the skin for heat dissipation. This, in turn causes oxygen levels to drop even further in the normally low oxygen environment of the gastrointestinal tract where it has been shown that low oxygen levels have negative impacts on gastrointestinal function. Thus, this study tested whether heat stress or low oxygen levels alone, or a combination of the two would cause GI damage and inflammation in a pig intestinal cell culture model. Results from this research determined that low oxygen levels were needed to cause disruptions in gastrointestinal function and inflammation and that elevated environmental temperatures alone did not cause these negative effects. This research provides research animal scientists, as well as human researchers, potential mechanisms for future studies aiming to mitigate heat stress effects on the gastrointestinal tract.

Technical Abstract: Heat stress (HS) negatively impacts human health, as well as animal agriculture. The objective of the current study was to tease out the effects of HS alone, and hypoxia alone while also examining the compound effects of a two-stressor system. The mechanisms underlying heat stress induced intestinal dysfunction in vivo are still not fully elucidated. However, heat stress has been shown to cause intestinal ischemia/hypoxia. Thus, we hypothesize that hypoxia is a critical factor and important step in the pathway to HS-induced barrier dysfunction. Porcine IPEC-J2 cells were grown in Transwell™ plates and then treated either under thermal neutral (TN; 38°C) or heat stress (HS; 42°C) and either normoxia (NX; ~21% O2) or hypoxia (HX; 1% O2) for 24 h. Transepithelial electrical resistance, media interleukin 8, cell HSP70 and 90, as well as localization of tight junction proteins CLDN4, ZO-1 and EEA1 were all analyzed. Results showed that HS did not cause intestinal permeability in this model, elicited a reduction in IL-8 while still exhibiting a robust HSP response. Hypoxia was required to induce intestinal barrier dysfunction and tight junction re-distribution in this model, in the absence of an IL-8 response under HS and the combinatorial effect was even more severe in terms of tight junction disruption.