Advances in Food Technology and Nutritional Sciences · Vol. 3, No. 1 · 2017 · pp. e1–e4 · e-ISSN 2377-8350

Heat Stress and Gut Health in Broilers: Role of Tight Junction Proteins

Guillermo Tellez Jr., Guillermo Tellez-Isaias, Sami Dridi

DOI: https://doi.org/10.17140/aftnsoj-3-e010 · Published 2017-09-05 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2017 The Author(s)

Abstract

Sixteen of the seventeen hottest years ever recorded have occurred since 2001 and climate trends are predicted to continue in an upward trend. As this upward trend continues, it will serve as a severe environmental stress factor on all forms of the life. One of the most affected industries will be the livestock industry.

INTRODUCTION Article Ref. #: 1000AFTNSOJ3e010

Sixteen of the seventeen hottest years ever recorded have occurred since 2001 and climate

Article History trends are predicted to continue in an

th Received: September 4 , 2017 serve as a severe environmental stress factor on all forms of the life. One of the most affected

th Accepted: September 5th, 2017 industries will be the livestock industry. Poultry, in particular, appears to be very heat sensi-

th Published: September 5 , 2017 tive animals, due to lack of sweat glands and high metabolic activity. It is estimated that heat

stress alone costs the U.S. poultry industry more than 100 million dollars a year and this num-

ber is expected to rise.6 For broiler (meat-type) chickens, the external temperature for optimal

Citation 7

performance is 18 to 22 ºC. Under these conditions, the internal body temperature of a broiler Tellez Jr. G, Tellez-Isaias G, Driis between 40.6 °C-41.7 °C. Nevertheless, when chickens are placed under heat stress condidi S. Heat stress and gut health

in broilers: Role of tight junction tions, their body temperature may be well above that; up to 45 °C-47.2 °C, which is the lethal

proteins. Adv Food Technol Nutr limit.8 Heat stress (HS) or hyperthermia results from failed thermoregulation that occurs when

Sci Open J. 2017; 3(1): e1-e4.

animals produce or absorbs more temperature than it dissipates. The adverse effects of HS can doi: 10.17140/AFTNSOJ-3-e010 range from discomfort to multiple organ damage and, under severe stress, to death by spiraling

hyperthermia. The Gut plays a vital role in nutrient absorption, digestion and transport, yet it is

very responsive and susceptible to HS.

on tight junction (TJ) proteins and gut health.

Heat Stress And Gut Health

Under thermoneutral conditions, the gut is able to efficiently digest and absorb most nutri-

ents through cell plasma membranes (transcellular transport) that involves specific receptors.

Epithelial cells in the intestine provides a barrier isolating the external environment from the

internal body, yet, providing tolerance to water and digested nutrients. Intestinal epithe-

lial cells adhere to each other through three distinct intercellular junctional complex known

as desmosomes, adheren junctions (AJ), and TJ (Figure 1). Desmosomes are localized dense

plaques that are connected to keratin filaments while AJ and TJ both consist of transcellular

proteins. These proteins are connected intracellularly through adaptor proteins to the actin

cytoskeleton.3,15 In contrast to transcellular transport, the transfer of molecules through the

space between the cells across an epithelium (paracellular transport) is passive down a con-

centration gradient, and this transport is regulated by the TJ.16 As multi-protein complexes, TJ

not only hold cells together, but they form channels allowing the transport of substances across

the epithelium.17 Interestingly, the molecular composition, ultrastructure, and function of TJ

is regulated by intracellular proteins through a series of intracellular signaling pathways that

includes myosin light kinase (MLCK), mitogen-activated protein kinases (MAPK), protein

kinase C (PKC) among others.18 Occludin phosphorylation on Tyr, Ser and Thr is associated

Copyright with disruption of TJ, hence, phosphorylation of occludin is involved in TJ permeability.19 Any

©2017 Dridi S. This is an open ac- factors that affect the balance between

cess article distributed under the stress or inflammation can affect gut permeability due to disruption of TJ. In contrast, gly- Creative Commons Attribution 4.0 cosylation of the Junctional adhesion molecule-A (JAM-A) decreases gut permeability. TJ International License (CC BY 4.0), which permits unrestricted use, regulate epithelial permeability and paracellular diffusion via two pathways, leak and pore.

distribution, and reproduction in The leak pathway allows transport of large noncharged solutes while the pore pathway allows

any medium, provided the original the transfer of large charged molecules. As transmembrane barrier proteins, TJ also function work is properly cited.

as a fence between the lumen and host. There are roughly 50 TJ proteins, which include the upward trend.1 As this upward trend continues, it will

2,3

4,5

In this editorial we will review the effect of heat stress

10-12

13,14

3,15

protein kinases and protein phosphatases, such as heat

20,21

22,23

Figure 1
Figure 1. Functions of Tight Junctions. Tight Junctions are the Pri- mary Mechanisms that Control the Epithelium (Tight or Leaky). Sev- eral Classes of Tight Junction Proteins including Claudins, JAM-A, and ZO-1/2 Play an Important in Cell Permeability.

claudins, occludin, tricellulin, JAM’s, and scaffolding proteins. For instance, tricellulin (also known as MARVELD2) and angulin

family proteins, including angulin-1 (also known as LSR), angulin-2 (also known as ILDR1) and angulin-3 (also known as ILDR2),

have been identified as molecular constituents of tricellular contacts. Both

as the full barrier function of epithelial cellular sheets. The primary role of scaffolding proteins is to regulate stand formation and

placement of transmembrane proteins. Under thermal neutral conditions, paracellular junction are rigorously regulated. How-

ever, under heat stress conditions, the TJ barrier becomes compromised and luminal substances leak into the blood stream, hence

the term leaky gut,28 a condition that induce chronic systemic inflammation which requires high resources of energy that impact

negatively the performance of the animals. Alterations in gut permeability

portal and/or systemic circulation in several types of leaky gut syndromes leading to systemic bacterial infections.29 Similarly, FITC-

dextrin is a large molecule (3-5 kDa) which does not usually leak through the intact gastrointestinal tract barrier.4,6 However, when

there are conditions which disrupt the tight junctions between epithelial cells, the molecule can enter circulation demonstrated by

an increase in trans-mucosal permeability associated with chemically induced disruption of tight junctions by elevated serum levels

30,31 of FITC-d after oral administration. Although studies are very limited, it has been reported that cyclic heat stress up regulated

claudin and ZO-1 expression in the chicken jejunum.32 This indicates that

induces leaky gut via alteration of tight junction proteins which merit further in depth investigations.

Conflicts Of Interest

The authors declare that they have no conflicts of interest.

References

  1. KarlTRTrenberthKE. Modern global climate change. Science. 2003; 302(5651): 1719-1723. doi: 10.1126/science.109022810.1126/science.1090228 https://doi.org/10.1126/science.1090228
  2. RothMSDeheynDD. Effects of cold stress and heat stress on coral fluorescence in reef-building corals. Sci Rep. 2013; 3: 1421. doi: 10.1038/srep0142110.1038/srep01421 https://doi.org/10.1038/srep01421
  3. MelilloJMMcGuireADKicklighterDWMooreBVorosmartyCJSchlossAL. Global climate change and terrestrial net primary production. Nature. 1993; 363(6426): 234-240. doi: 10.1038/363234a0 types of proteins are involved in TJ formation as well 4,27 14 are associated with bacterial translocation (BT) in the 4,6 heat stress dysregulates intestinal barrier function and 185-190. doi: 10.3923/ijps.2006.185.19010.1038/363234a0 https://doi.org/10.1038/363234a0
  4. PrietoMCampoJ. Effect of heat and several additives related to stress levels on fluctuating asymmetry, heterophil: Lymphocyte ratio, and tonic immobility duration in White Leghorn chicks. Poult Sci. 2010; 89(10): 2071-2077. doi: 10.3382/ps.2010-0071610.3382/ps.2010-00716 https://doi.org/10.3382/ps.2010-00716
  5. St-PierreNCobanovBSchnitkeyG. Economic losses from heat stress by US livestock industries. J Dairy Sci. 2003; 86: E52-E77. doi: 10.3168/jds.S0022-0302(03)74040-510.3168/jds.s0022-0302(03)74040-5 https://doi.org/10.3168/jds.s0022-0302(03)74040-5
  6. Borges SA, Fischer da Silva AV, Ariki J, Hooge DM, Cummings KR. Dietary electrolyte balance for broiler chickens exposed to thermoneutral or heat-stress environments. Poult Sci. 2003; 82(3): 428-435. doi: 10.1093/ps/82.3.428 https://doi.org/10.1093/ps/82.3.428
  7. MohanaselvanABhaskarE. Mortality from non-exertional heat stroke still high in India. Int J Occup Environ Med. 2014; 5(4):
  8. LaraLJRostagnoMH. Impact of heat stress on poultry production. Animals. 2013; 3(2): 356-369. doi: 10.3390/ani302035610.3390/ani3020356 https://doi.org/10.3390/ani3020356
  9. SalzmanNH. Microbiota-immune system interaction: An uneasy alliance. Curr Opin Microbiol. 2011; 14(1): 99-105. doi: 10.1016/j.mib.2010.09.01810.1016/j.mib.2010.09.018 https://doi.org/10.1016/j.mib.2010.09.018
  10. ElsonCOCongY. Host-microbiota interactions in inflammatory bowel disease. Gut Microbes. 2012; 3(4): 332-344. doi: 10.4161/gmic.2022810.4161/gmic.20228 https://doi.org/10.4161/gmic.20228
  11. SalminenSIsolauriE. Intestinal colonization, microbiota, and probiotics. J Pediatr. 2006; 149(5): S115-S120. doi: 10.1016/j. jpeds.2006.06.06210.1016/j.jpeds.2006.06.062 https://doi.org/10.1016/j.jpeds.2006.06.062
  12. CumminsPM. Occludin: One protein, many forms. Mol Cell Biol. 2012; 32(2): 242-250. doi: 10.1128/MCB.06029-1110.1128/mcb.06029-11 https://doi.org/10.1128/mcb.06029-11
  13. Di PierroMLuRUzzauS. Zonula occludens toxin structure-function analysis Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J Biol Chem. 2001; 276(22): 19160-19165. doi: 10.1074/jbc. M00967420010.1074/jbc.m009674200 https://doi.org/10.1074/jbc.m009674200
  14. AssimakopoulosSFPapageorgiouICharonisA. Enterocytes’ tight junctions: From molecules to diseases. World J Gastrointest Pathophysiol. 2011; 2(6): 123. doi: 10.4291/wjgp.v2.i6.12310.4291/wjgp.v2.i6.123 https://doi.org/10.4291/wjgp.v2.i6.123
  15. HuYJWangYDTanFQYangWX. Regulation of paracellular permeability: Factors and mechanisms. Mol Biol Rep. 2013; 40(11): 6123-6142. doi: 10.1007/s11033-013-2724-y10.1007/s11033-013-2724-y https://doi.org/10.1007/s11033-013-2724-y
  16. AwadWBohmJRazzazi-FazeliEGhareebKZentekJ. Effect of addition of a probiotic microorganism to broiler diets contaminated with deoxynivalenol on performance and histological alterations of intestinal villi of broiler chickens. Poult Sci. 2006; 85(6): 974-979
  17. HeHKogutMH. CpG-ODN-induced nitric oxide production is mediated through clathrin-dependent endocytosis, endosomal maturation, and activation of PKC, MEK1/2 and p38 MAPK, and NFkappaB pathways in avian macrophage cells (HD11). Cellular signalling. 2003; 15(10): 911-917. doi: 10.1016/S0898-6568(03)00100-110.1016/s0898-6568(03)00100-1 https://doi.org/10.1016/s0898-6568(03)00100-1
  18. MurakamiTFelinskiEAAntonettiDA. Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor-induced permeability. J Biol Chem. 2009; 284(31): 21036-21046. doi: 10.1074/jbc.M109.01676610.1074/jbc.m109.016766 https://doi.org/10.1074/jbc.m109.016766
  19. QinLHuangWMoXChenYWuX. LPS induces occludin dysregulation in cerebral microvascular endothelial cells via MAPK signaling and augmenting MMP-2 levels. Oxid Med Cell Longev. 2015; 2015. doi: 10.1155/2015/12064110.1155/2015/120641 https://doi.org/10.1155/2015/120641
  20. MuthusamyALinCMShanmugamSLindnerHMAbcouwerSFAntonettiDA. Ischemia-reperfusion injury induces occludin phosphorylation/ubiquitination and retinal vascular permeability in a VEGFR-2-dependent manner. J Cereb Blood Flow Metab. 2014; 34(3): 522-531. doi: 10.1038/jcbfm.2013.23010.1038/jcbfm.2013.230 https://doi.org/10.1038/jcbfm.2013.230
  21. SuzukiTEliasBCSethA. PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci USA. 2009; 106(1): 61-66. doi: 10.1073/pnas.080274110610.1073/pnas.0802741106 https://doi.org/10.1073/pnas.0802741106
  22. HiraseTKawashimaSWongEY. Regulation of tight junction permeability and occludin phosphorylation by Rhoap160ROCK-dependent and-independent mechanisms. J Biol Chem. 2001; 276(13): 10423-10431. doi: 10.1074/jbc.M00713620010.1074/jbc.m007136200 https://doi.org/10.1074/jbc.m007136200
  23. MurakamiTFreyTLinCAntonettiDA. Protein kinase C$\beta$ phosphorylates occludin regulating tight junction trafficking in vascular endothelial growth factor-induced permeability in vivo. Diabetes. 2012; 61(6): 1573-1583. doi: 10.2337/db11-136710.2337/db11-1367 https://doi.org/10.2337/db11-1367
  24. Al-SadiRYeDDokladnyKMaTY. Mechanism of IL-1$\beta$-induced increase in intestinal epithelial tight junction permeability. J Immunol. 2008; 180(8): 5653-5661. doi: 10.4049/jimmunol.180.8.565310.4049/jimmunol.180.8.5653 https://doi.org/10.4049/jimmunol.180.8.5653
  25. TurnerJRAngleJMBlackEDJoyalJLSacksDBMadaraJL. PKC-dependent regulation of transepithelial resistance: Roles of MLC and MLC kinase. Am J Physiol. 1999; 277(3 Pt 1): C554-C562
  26. TurnerJRRillBKCarlsonSL. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol. 1997; 273(4 Pt 1): C1378-C1385
  27. BosenbergATBrock-UtneJGGaffinSLWellsMTBlakeGT. Strenuous exercise causes systemic endotoxemia. J Appl Physiol. 1988; 65(1): 106-108
  28. IlanY. Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol. 2012; 18(21): 2609. doi: 10.3748/wjg.v18.i21.260910.3748/wjg.v18.i21.2609 https://doi.org/10.3748/wjg.v18.i21.2609
  29. BaxterMFMerino-GuzmanRLatorreJD. Optimizing fluorescein isothiocyanate dextran measurement as a biomarker in a 24-h feed restriction model to induce gut permeability in broiler chickens. Front Vet Sci. 2017; 4. doi: 10.3389/fvets.2017.0005610.3389/fvets.2017.00056 https://doi.org/10.3389/fvets.2017.00056
  30. YanYKolachalaVDalmassoG. Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis. PLoS One. 2009; 4(6): e6073. doi: 10.1371/journal.pone.000607310.1371/journal.pone.0006073 https://doi.org/10.1371/journal.pone.0006073
  31. VarastehSBraberSAkbariPGarssenJFink-GremmelsJ. Differences in susceptibility to heat stress along the chicken intestine and the protective effects of galacto-oligosaccharides. PLoS One. 2015; 10(9): e0138975. doi: 10.1371/journal.pone.013897510.1371/journal.pone.0138975 https://doi.org/10.1371/journal.pone.0138975