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Rius, A. Heat Stress Affect Intestinal Mucosa. Encyclopedia. Available online: https://encyclopedia.pub/entry/20106 (accessed on 20 July 2025).
Rius A. Heat Stress Affect Intestinal Mucosa. Encyclopedia. Available at: https://encyclopedia.pub/entry/20106. Accessed July 20, 2025.
Rius, Agustin. "Heat Stress Affect Intestinal Mucosa" Encyclopedia, https://encyclopedia.pub/entry/20106 (accessed July 20, 2025).
Rius, A. (2022, March 02). Heat Stress Affect Intestinal Mucosa. In Encyclopedia. https://encyclopedia.pub/entry/20106
Rius, Agustin. "Heat Stress Affect Intestinal Mucosa." Encyclopedia. Web. 02 March, 2022.
Heat Stress Affect Intestinal Mucosa
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This entry is adapted from the peer-reviewed paper 10.3390/antibiotics10111285

Metabolic adaptations and gut dysfunction lead to oxidative stress, translocation of lumen contents, and release of proinflammatory mediators, activating a systemic inflammatory response.

heat stress heat shock protein intestine

1. Structural Aspects

Exposure to high ambient temperatures may result in structural changes in the small intestine of rodents, poultry, and livestock [1][2][3][4][5][6][7][8][9][10]. The intestinal epithelium is composed of a single layer of cells that lines the inner surface of the small and large intestine, which, in addition to providing a solid protective barrier, functions as a very precise absorptive machinery. In mammals and birds, this cell line folds along its path through the GIT to increase its contact surface and thus its absorptive power, generating villi (raised portions) and invaginations between villi, which are termed crypts. In vivo models for studying gut physiology have shown hyperplastic crypts combined with reduced villus area, suggesting rapid tissue adaptation to nutrient shortages [11][12][13]. Heat stress may affect the intestinal structure by shortening villus height and increasing crypt depth, with a consequent decrease in the villus:crypt ratio, as shown in poultry [2][3][5][6][14], rodents [15][8], and pigs [16][4] (Table 1). The aforementioned effects have been found in different heat-stressed animal models (i.e., ambient temperatures from 33 to 39 °C for 1.5 to 24 h/day, and duration of insult from 1 to 30 days). Furthermore, heat stress has led to epithelial desquamation at the tips of villi and exposure of the lamina propria in the duodenum and jejunum of pigs (i.e., ambient temperature of 40 °C for 2–5 h) [9][10] and in the jejunum and ileum of rats (i.e., ambient temperature of 40 °C for 2 h/day for 10 days [7] or 3 days [17]). Although the direct effect of heat may result in epithelial loss [18], the shift in blood flow away from the gut with a concomitant shortage in nutrient supply to the intestine may contribute to the alterations in intestinal architecture observed in heat-stressed animals.
Table 1. Structural changes in the intestinal epithelium of different animals subjected to hyperthermia.
Animal Model Heat Stress Protocol 1 Days of Sampling 2 Tissue Villus Height Crypt Depth V:C 5 Ref. 6
Change 3 % 4 Change % Change %
Broilers 33 °C–10 h/day–20 days 20 Jejunum ↓ 18.5 ↑ 10.0 ↓ 23.3 [2]
Broilers 39 ± 1 °C–8 h/day–4 days 4 Duodenum ↓ 18.4 = - ↓ 50.5 [3]
      Jejunum ↓ 17.6 ↑ 17.0 = -  
      Ileum ↓ 20.2 = - ↓ 40.0  
Broilers 37 ± 2 °C–8 h/day–15 days 15 Jejunum ↓ 27.7 ↑ 28.2 ↓ 43.1 [14]
      Ileum ↓ 24.7 ↑ 28.8 ↓ 37.0  
Broilers 37 ± 1 °C —10 h/day–21 days 21 Jejunum ↓ 18.6 ↑ 38.2 ↓ 39.1 [6]
Broilers 33 ± 0.5 °C–3 h/day–1 day 1 Ileum = - = - = - [5]
    7 † Ileum ↓ 22.6 ↑ 14.5 ↓ 31.4  
Rats 40 °C–2 h/day–10 days 3 Duodenum ↓ 21.9 ↓ 36.4 NA7 NA [7]
      Jejunum ↓ 33.1 ↓ 30.5 NA NA  
      Ileum ↓ 36.1 ↓ 32.5 NA NA  
Rats 40 ± 1 °C–1.5 h/day–3 days 3 Jejunum ↓ 22.2 = - ↓ 30.6 [8]
Rats 35 ± 1 °C–4 h/day–7 days 7 Duodenum ↓ 14.8 = - = - [15]
      Jejunum ↓ 28.9 = - = -  
      Ileum ↓ 36.8 = - ↓ 21.0  
Pigs 40 °C–5 h/day–10 days 1 Duodenum ↓ 12.3 = - = -  
      Jejunum ↓ 20.8 ↓ 17.4 ↓ 6.3 [9]
      Ileum ↓ 11.2 = - = -  
    3 Duodenum ↓ 11.8 ↓ 23.1 ↑ 13.3  
      Jejunum ↓ 18.8 ↓ 22.1 = -  
      Ileum ↓ 10.4 = - = -  
Pigs 40 °C–5 h/day–10 days 1 Duodenum ↓ 8.8 = - NA NA [10]
      Jejunum ↓ 21.3 ↓ 15.9 NA NA  
      Ileum = - = - NA NA  
    3 Duodenum ↓ 10.6 = - NA NA  
      Jejunum ↓ 22.2 ↓ 18.7 NA NA  
      Ileum ↓ 9.7 = - NA NA  
Pigs 35 ± 1 °C–24 h/day–7 days 1 Jejunum ↓ 14.6 ↑ 5.2 ↓ 17.6 [4]
    3 Jejunum ↓ 20.4 ↑ 4.5 ↓ 23.5  
    7 Jejunum ↓ 22.9 ↓ 4.5 ↓ 17.6  
Pigs 35 °C–12 h/day–30 days 30 Jejunum ↓ NA = - ↓ NA [16]

1 Heat stress protocol, including maximum temperature (°C), intensity (hours of maximum temperature per day) and duration (number of days applying the protocol). 2 Day when the animals in the experiment (or some of them) were sacrificed and samples of intestine were taken to evaluate the structural changes in the epithelium. † In this experiment, heat stress was applied for 24 h and samples of intestine were collected 7 days after the heat stress insult. 3 Change elicited by heat stress relative to thermoneutral treatment (increase (↑) or decrease (↓) when p < 0.05, and without differences (=) when p > 0.05). 4 Percentage of change (increase or decrease). 5 Villus height to crypt depth ratio. 6 Reference. 7 Not available.

 

 

Changes in the epithelial ultrastructure of the jejunum have been found in animals exposed to heat stress. Electron microscopy analysis revealed that a large amount of inflamed fibrous substances flow out of the hyperthermic rat jejunal epithelium [17]. In pigs and rats, heat stress (40 °C for 2–5 h/day for 10 days) affects epithelial cells of the jejunum, shortens microvillus height and increases the number of mitochondria with shortened internal cristae and secondary lysosomes compared with the jejunum in thermoneutral (TN) animals [7][9][10]. Vacuolization in the epithelium in the jejunum of rats exposed to heat stress has also been reported, possibly in association with the progressive loss of epithelial cells [7]. Although these changes in cellular structure and ultrastructure have been observed in all portions of the SI, it seems that the jejunum has greater susceptibility than other segments of the GIT [9][10][17].
In addition to loss of the epithelium of villi, the metabolic alterations generated by heat stress in the intestinal stem cells at the bottom of crypts may delay epithelial cell turnover and replenishment. Intestinal stem cells exhibit a high regenerative power that ensures the turnover of most mature epithelial cells in less than five days [19]; however, exposure to high temperatures can alter the proliferation and apoptosis of intestinal stem cells. As recently demonstrated by Zhou et al. [20] using in vitro models, continuous heat exposure at 41 °C for 72 h of undifferentiated porcine jejunal epithelial cells inhibits cell proliferation and increases apoptosis via inhibition of the Wnt/β-catenin pathway, the main signal that activates the proliferation of intestinal epithelial cells in the depth of intestinal crypts [21].

2. Functional Aspects

Stressful events such as exposure to heat can alter the permeability of the intestine to luminal contents (e.g., nutrients and markers) [18][22][23][24]. As alterations in intestinal permeability may reveal changes in absorptive mechanisms (e.g., paracellular pore and leak pathways), this approach is used to assess intestinal function. Gut permeability can be studied by measuring the passage of markers such as fluorescein isothiocyanate-dextran (FITC-D), creatinine, cobalt-EDTA, lactulose and mannitol in vivo and by measuring transepithelial electrical resistance (TER) and permeability to horseradish peroxidase ex vivo and in vitro. Studies have shown that FITC-D increases while TER decreases in the jejunum and/or ileum of pigs and poultry exposed to heat stress [25][2][6][23][26][27][28], indicating an increase in mucosal permeability. In pigs subjected to heat stress (31 ± 1 °C, 12 h/day for 7 days), it was determined that ileum and colon permeability increased, as indicated by a larger lactulose: mannitol ratio [29]. Furthermore, increased intestinal permeability was observed in mice [18][30] exposed to heat stress. In vitro studies have demonstrated increases in permeability or decreases in TER in cultures of epithelial cells, such as intestinal epithelial cell-6 (IEC-6) [30], porcine jejunal cell line (IEC-J2) [29], and human colon-derived crypt-like cells T84 [31] exposed to heat treatments.
Tight junctions (TJs) and adherent junction proteins play a key role in controlling the permeability of the intestinal epithelium [18][32] and in controlling the passage of nutrients via the paracellular space between adjacent cells [33]. Expression of TJ proteins (i.e., occludin and zonula occludens-1 (ZO-1) in the jejunum [2] of chickens and ZO-1 in the jejunum of dairy cows [22]) was reduced during heat stress, and heat stress reduced expression of occludin and claudin-3 in the ileum of pigs [25]. Such an increase in occludin expression was also reported in a study with Caco-2 cells exposed to heat [34]. Gene expression analyses showed higher mRNA expression of claudin-5 and ZO-1 in the jejunum and claudin-1 and -5 and ZO-1 in the ileum in heat-stressed broilers [35]. It was reported that in pigs, heat stress increases the mRNA abundance of occludin, ZO-1 and claudin genes (i.e., pig jejunum after exposure to constant 35 °C for 7 days [4]); in dairy cows, heat stress increases the mRNA abundance of the ZO-1 and claudin-3 genes (i.e., cow jejunum after constant 28 °C for 4 days [22]). However, mRNA levels of occludin, ZO-1, and claudin-1 genes decrease in the jejunum [2][6] of heat-stressed broilers. These contradictory results can be attributed in part to differences between species and studies concerning the duration and severity of heat exposure. It is possible that permeability changes associated with heat stress are mediated by altering expression of TJs in the intestinal epithelium. This relationship has been described in both in vivo and in vitro models of enteritis, aiming to better understand the role of cellular mechanisms to prevent and treat the clinical conditions of humans. Heat stress may lead to changes in TJ expression in the epithelium, but the role of these changes in intestinal permeability remains elusive.

References

  1. Hall, D.M.; Buettner, G.R.; Oberley, L.W.; Xu, L.; Matthes, R.D.; Gisolfi, C.V. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am. J. Physiol.—Heart Circ. Physiol. 2001, 280, 509–521.
  2. Song, J.; Xiao, K.; Ke, Y.L.; Jiao, L.F.; Hu, C.H.; Diao, Q.Y.; Shi, B.; Zou, X.T. Effect of a probiotic mixture on intestinal microflora, morphology, and barrier integrity of broilers subjected to heat stress. Poult. Sci. 2014, 93, 581–588.
  3. Santos, R.R.; Awati, A.; Roubos-van den Hil, P.J.; Tersteeg-Zijderveld, M.H.G.; Koolmees, P.A.; Fink-Gremmels, J. Quantitative histo-morphometric analysis of heat-stress-related damage in the small intestines of broiler chickens. Avian Pathol. 2015, 44, 19–22.
  4. Pearce, S.C.; Mani, V.; Weber, T.E.; Rhoads, R.P.; Patience, J.F.; Baumgard, L.H.; Gabler, N.K. Heat stress and reduced plane of nutrition decreases intestinal integrity and function in pigs. J. Anim. Sci. 2013, 91, 5183–5193.
  5. Wickramasuriya, S.S.; Kim, E.; Cho, H.M.; Shin, T.K.; Kim, B.; Lee, M.; Seo, S.; Heo, J.M.; Choi, H. Differential effects of dietary methionine isomers on broilers challenged with acute heat stress. J. Poult. Sci. 2019, 56, 195–203.
  6. Zhang, C.; Zhao, X.H.; Yang, L.; Chen, X.Y.; Jiang, R.S.; Jin, S.H.; Geng, Z.Y. Resveratrol alleviates heat stress-induced impairment of intestinal morphology, microflora, and barrier integrity in broilers. Poult. Sci. 2017, 96, 4325–4332.
  7. Yu, J.; Liu, F.; Yin, P.; Zhao, H.; Luan, W.; Hou, X.; Zhong, Y.; Jia, D.; Zan, J.; Ma, W.; et al. Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine. Stress 2013, 16, 99–113.
  8. Cheng, K.; Song, Z.; Li, S.; Yan, E.; Zhang, H.; Zhang, L.; Wang, C.; Wang, T. Effects of resveratrol on intestinal oxidative status and inflammation in heat-stressed rats. J. Therm. Biol. 2019, 85, 102415.
  9. Liu, F.; Yin, J.; Du, M.; Yan, P.; Xu, J.; Zhu, X.; Yu, J. Heat-stress-induced damage to porcine small intestinal epithelium associated with downregulation of epithelial growth factor signaling. J. Anim. Sci. 2009, 87, 1941–1949.
  10. Yu, J.; Yin, P.; Liu, F.; Cheng, G.; Guo, K.; Lu, A.; Zhu, X.; Luan, W.; Xu, J. Effect of heat stress on the porcine small intestine: A morphological and gene expression study. Comp. Biochem. Physiol. Part A 2010, 156, 119–128.
  11. Burrin, D.G.; Stoll, B.; Jiang, R.; Chang, X.; Hartmann, B.; Holst, J.J.; Greeley, G.H.; Reeds, P.J. Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: How much is enough? Am. J. Clin. Nutr. 2000, 71, 1603–1610.
  12. Hossain, M.S.; Begum, S.M.K.N.; Rahman, M.M.; Mazumder, R.N.; Parvez, M.; Gazi, M.A.; Hasan, M.M.; Fahim, S.M.; Das, S.; Mahfuz, M.; et al. Alterations in the histological features of the intestinal mucosa in malnourished adults of Bangladesh. Sci. Rep. 2021, 11, 2355.
  13. Nilaweera, K.N.; Speakman, J.R. Regulation of intestinal growth in response to variations in energy supply and demand. Obes. Rev. 2018, 19, 61–72.
  14. Liu, L.; Fu, C.; Yan, M.; Xie, H.; Li, S.; Yu, Q.; He, S.; He, J. Resveratrol modulates intestinal morphology and HSP70/90, NF-κB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. Food Funct. 2016, 7, 1329–1338.
  15. Wei, L.; Li, Y.; Chang, Q.; Guo, G.; Lan, R. Effects of chitosan oligosaccharides on intestinal oxidative stress and inflammation response in heat stressed rats. Exp. Anim. 2020, 70, 45–53.
  16. Yi, H.; Xiong, Y.; Wu, Q.; Wang, M.; Liu, S.; Jiang, Z.; Wang, L. Effects of dietary supplementation with l-arginine on the intestinal barrier function in finishing pigs with heat stress. J. Anim. Physiol. Anim. Nutr. 2020, 104, 1134–1143.
  17. Liu, X.; Li, H.; Lu, A.; Zhong, Y.; Hou, X.; Wang, N.; Jia, D.; Zan, J.; Zhao, H.; Xu, J.; et al. Reduction of intestinal mucosal immune function in heat-stressed rats and bacterial translocation. Int. J. Hyperth. 2012, 28, 756–765.
  18. Lambert, G.P.; Gisolfi, C.V.; Berg, D.J.; Moseley, P.L.; Oberley, L.W.; Kregel, K.C. Selected Contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J. Appl. Physiol. 2002, 92, 1750–1761.
  19. Darwich, A.S.; Aslam, U.; Ashcroft, D.M.; Rostami-Hodjegan, A. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans. Drug Metab. Dispos. 2014, 42, 2016–2022.
  20. Zhou, J.; Huang, D.; Zhu, M.; Gao, C.; Yan, H.; Li, X.; Wang, X. Wnt/β-catenin-mediated heat exposure inhibits intestinal epithelial cell proliferation and stem cell expansion through endoplasmic reticulum stress. J. Cell. Physiol. 2020, 235, 5613–5627.
  21. Van Der Flier, L.G.; Clevers, H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 2009, 71, 241–260.
  22. Koch, F.; Thom, U.; Albrecht, E.; Weikard, R.; Nolte, W.; Kuhla, B.; Kuehn, C. Heat stress directly impairs gut integrity and recruits distinct immune cell populations into the bovine intestine. Proc. Natl. Acad. Sci. USA 2019, 116, 10333–10338.
  23. Sanz Fernandez, M.V.; Pearce, S.C.; Gabler, N.K.; Patience, J.F.; Wilson, M.E.; Socha, M.T.; Torrison, J.L.; Rhoads, R.P.; Baumgard, L.H. Effects of supplemental zinc amino acid complex on gut integrity in heat-stressed growing pigs. Animal 2014, 8, 43–50.
  24. Moseley, P.L.; Gapen, C.; Wallen, E.S.; Walter, M.E.; Peterson, M.W. Thermal stress induces epithelial permeability. Am. J. Physiol.—Cell Physiol. 1994, 267, 425–434.
  25. Pearce, S.C.; Mani, V.; Boddicker, R.L.; Johnson, J.S.; Weber, T.E.; Ross, J.W.; Rhoads, R.P.; Baumgard, L.H.; Gabler, N.K. Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs. PLoS ONE 2013, 8, e70215.
  26. Liu, F.; Cottrell, J.J.; Furness, J.B.; Rivera, L.R.; Kelly, F.W.; Wijesiriwardana, U.; Pustovit, R.V.; Fothergill, L.J.; Bravo, D.M.; Celi, P.; et al. Selenium and vitamin E together improve intestinal epithelial barrier function and alleviate oxidative stress in heat-stressed pigs. Exp. Physiol. 2016, 101, 801–810.
  27. Gabler, N.K.; Koltes, D.; Schaumberger, S.; Murugesan, G.R.; Reisinger, N. Diurnal heat stress reduces pig intestinal integrity and increases endotoxin translocation. Transl. Anim. Sci. 2018, 2, 1–10.
  28. Goo, D.; Kim, J.H.; Park, G.H.; Reyes, J.B.D.; Kil, D.Y. Effect of heat stress and stocking density on growth performance, breast meat quality, and intestinal barrier function in broiler chickens. Animals 2019, 9, 107.
  29. Mani, V.; Rubach, J.K.; Sanders, D.J.; Pham, T.; Koltes, D.A.; Gabler, N.K.; Poss, M.J. Evaluation of the protective effects of zinc butyrate in IPEC-J2 cells and grower pigs under heat stress. Transl. Anim. Sci. 2019, 3, 842–854.
  30. He, S.; Liu, F.; Xu, L.; Yin, P.; Li, D.; Mei, C.; Jiang, L.; Ma, Y.; Xu, J. Protective effects of ferulic acid against heat stress-induced intestinal epithelial barrier dysfunction in vitro and in vivo. PLoS ONE 2016, 11, e0145236.
  31. Yang, P.C.; He, S.H.; Zheng, P.Y. Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function. J. Gastroenterol. Hepatol. 2007, 22, 1823–1831.
  32. Turner, J.R. Intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 2009, 9, 799–809.
  33. Nasu, Y.; Ido, A.; Tanoue, S.; Hashimoto, S.; Sasaki, F.; Kanmura, S.; Setoyama, H.; Numata, M.; Funakawa, K.; Moriuchi, A.; et al. Hepatocyte growth factor stimulates the migration of gastric epithelial cells by altering the subcellular localization of the tight junction protein ZO-1. J. Gastroenterol. 2013, 48, 193–202.
  34. Dokladny, K.; Ye, D.; Kennedy, J.C.; Moseley, P.L.; Ma, T.Y. Cellular and molecular mechanisms of heat stress-induced up-regulation of occludin protein expression: Regulatory role of heat shock factor-1. Am. J. Pathol. 2008, 172, 659–670.
  35. Varasteh, S.; Braber, S.; Akbari, P.; Garssen, J.; Fink-Gremmels, J. Differences in susceptibility to heat stress along the chicken intestine and the protective effects of galacto-oligosaccharides. PLoS ONE 2015, 10, e0138975.
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