Table 2. Effect of heat stress on mucosal morphology, antioxidant status, integrity, immunity, and production performance in the gut of farm animals

Reference Animal TN vs. HS conditions with RH Major effect in comparison with TN versus HS conditions
[130] 21-day old male broiler chickens TN (21°C) vs. HS (32°C) with 64% RH for 14 days ● HS decreased BW, ADG and increased FCR● HS decreased villus length, villus surface area, epithelium cell area, and relative weight of intestine.
[66] Lohmann LSL-classic layer cockerels TN (21°C, RH 62%) vs. HS (35°C, 64% RH, from 09:00 to 13:00 and rest of the time at 21°C for 30 days ● HS decreased duodenal, jejunal and ileal villus height, crypt depth and absorptive epithelial cell area.● Sloughing of epithelial cells of tips and sides of villus, vacuolization, and desquamation of mucosal epithelia with denuded lamina propria.
[63] 26-day-old broiler chickens TN (20°C, 24 h/day) vs. HS (30°C, 24 h/day and 35°C for 4 h/day and then 20°C for 18 h) for 10 days ● HS reduced BW, ADG and increased FCR. Feed intake increased in the acute HS condition.● Increased lipopolysaccharide, corticosterone, TNFA, and IL2 in blood, and a higher prevalence of Salmonella spp. in livers and meat.
[12] Male Ross 308 broiler chickens TN (23°C) vs. HS (30°C) for 24 h ● Ileal tissue had fewer bands on HS than TN.● Crypt depth reduced but no effect on villus height and VCR after 24 h of HS.
[131] Male Wenchang chickens TN (25.7°C, 79 to 88% RH) vs. HS (40.5°C, 52.4% RH 2 h/day) for 15 days ● Small intestinal mucosal epithelial cells dispersed outwards, indicative of compromised structural integrity.● Mucosal epithelia were detached with ruptured small intestinal villi and exposed lamina propria.● HS reduced in villus length, mucosa thickness, intestinal wall thickness, and crypt depth in all three segments.
[97] Male Wenchang chickens Ambient temperature vs. HS (40.5°C, 52.4% RH for 2 h) for 15 days ● HS declined BW, ADG, and feed intake, but no effect on FCR.● HS decreased villus length, crypt depth, mucosa thickness, and intestinal wall thickness in duodenum and ileum, and goblet cells in duodenum and jejunum.
[76] Male Arbor Acres plus broiler chickens TN (20°C) vs. HS (32°C–33°C 8 h/day) for 42 days ● HS decreased ADG, ADFI, and FCR.● HS increased jejunal mucosal MDA content, and lowered SOD activity in ileal mucosa at 42 day.● HS reduced villi height and VCR in jejunum and ileum, and increased jejunal crypt depth.● HS decreased mRNA abundance of CLDN3 in jejunum, but not in ileum at 21 days.● HS reduced mRNA levels of jejunal MUC2 and OCLN, and ileal MUC2, ZO1, OCLN, and CLDN3 at 42 days.
[132] Castrated crossbred male pigs TN (22°C) vs. HS (30°C) and 55% RH for 21 days ● HS reduced villus height and crypt depth, but no effect on VCR.● HS increased plasma D-lactate concentration and lowered alkaline phosphatase activity in intestinal mucosa.● HS upregulated HSPH1, HSPB1, HSPA5, and HSPA1A.
[90] White Leghorn hens (350-day-old) TN (20°C–22°C, 50%–60% RH) vs. HS (30°C–33°C, 70%–80% RH for 24 h) for 28 days ● HS decreased egg weight, eggshell thickness, eggshell percentage, and eggshell density.● HS decreased calcium binding protein (calbindin) in ileum, cecum, and colon.
[61] 1-week post-weaned crossbred gilts TN (28°C) vs. HS (38°C for 6 h/day and rest 18 h/day at 32°C) with 40%–60% RH for 3 days ● TER reduced in ileum.● FITC-d and FITC-LPS flux increased in ileum.● HSP70 protein increased in ileum.
[89] Male broiler chickens (28 days old) TN (20°C, 50% RH) vs. HS (30°C, 70% RH) vs. pair-feeding like HS in TN for 14 days ● HS and pair-feeding reduced BW gain.● Only HS lowered plasma thyroid hormones and increased corticosterone than TN and pair feeding groups.● HS reduced fresh weight and length of jejunum compared to TN and pair-feeding.● No change in proximal end of jejunum, but villus length reduced on HS, followed by pair feeding and then TN.● HS increased the activity and expression of apical SGLT1 by approximately 50%, with no effects in the pair-feeding group.
[77] 21-day-old mixed Cobb broiler chickens TN (20°C) vs. HS (27.8°C) with 53.0% RH for 14 days (21 to 35 days of age) ● HS decreased BW, ADG, ADFI, and feed efficiency. Breast meat quality was not affected by HS.● HS decreased jejunal TER values.● No effect on serum LPS concentration.● HS had no effect on jejunal gene expressions of OCLN, ZO1, CLDN1, and JAM2.
[84] Male broiler chickens TN (21°C) vs. HS (0, 2, 3, 5 and 10 h at 36°C for a day ● In jejunal mucosa, HS decreased level of lactic acid dehydrogenase in 3, 5 and 10 h, but no change of GPx.● In jejunum, SOD increased after 2 h of HS, but T-AOC tended to increase with HS time and peaked at 10 h after HS.● HS increased T-AOC and MDA content after 10 h in jejunum.
[68] German Holstein cows Pair-feeding (15°C, 63% RH) vs. HS (28°C, 52% RH) for 4 days ● Villus height and crypt depth of jejunum was not affected.● HS increased number of infiltrating cells in submucosa of jejunum but not in mucosa.● HS increased ZO1 and tended to increase CLDN1 mRNA abundance in jejunum.● HS tended to lower ZO1 protein abundance, but CLDN1 protein was similar in jejunum.● No significant differences for MLCK, ZO2, and OCLN mRNA abundances.No effect on TNFA, IL6, IL10, CXCL5, and haptoglobin mRNA levels, but IL4 mRNA expression tended to be higher in jejunum of HS animals.● No effect on IL1β and IL4 protein levels in jejunum.● HS tended to increase catalase mRNA expression, but mRNA abundances of SOD1 and GPx1 were similar.● No effect on catalase and lysozyme activities, but HS increased alkaline phosphatase activity in jejunal mucosa.
[133] Crossbred pigs 50% male and 50% female TN (21°C–23°C, 30.2% RH for 6 h) vs. HS (39.3°C, 15.9% RH for 3 h followed by rapid cooling to TN or gradual cooling in 3 h to TN) ● Jejunum and ileum villus height was reduced in gradual cooling pigs compared to rapid cooling and TN pigs.● Jejunum and ileum VCR reduced in gradual cooling pigs.● On day 4, FITC-d permeability was higher than on day 0.● Jejunal CLDN1 gene expression was higher on day 0 than on day 4, but Ileal CLDN1 gene expression was lower for gradual cooling than for TN on day 2, and was higher for gradual cooling than for rapid cooling and TN on day 4.● Increased ZO1 gene expression in gradual cooling pigs.
[134] Male Arbor Acres broilers from 28 to 42 days TN (23°C) vs. cyclic HS (28°C–35°C–28°C for 12 h daily) for 21 days ● HS lower ADFI, ADG, and feed conversion ratio.● HS reduced villus height and VCR in duodenum and jejunum on day 28.● HS increased serum D-lactic acid concentration on day 28.● HS increased serum TNFA, IL6 levels and tended to increase pro-inflammatory cytokine IL1β, but decreased anti-inflammatory cytokine IL10 levels.
[69] 2-month-old male Chinese mini pigs TN (23°C) vs. HS (40°C, 5 h/day for 10 days) ● HS decreased villus height in duodenum and jejunum on day 3.● Crypt depth in duodenum and jejunum was shallower, but iIleal crypt depth was similar.● HS increased VCR on day 3, but no effect on day 6 in duodenum. HS increased VCR on day 1 in jejunum, and no effect in ileum.● HS increased mitochondria numbers with shortened internal cristae in jejunal epithelium.● HS decreased protein expression of EGF in jejunum.● Desquamation found at tips of intestinal villi, and exposed lamina propria in jejunum.
[71] 28 day old female Xuefeng black-boned chickens TN (24°C for 24 h/day) vs. HS (37°C for 8 h/day; remaining 16 h/day at 24°C) for 15 days ● HS reduced intestinal villi and VCR, deepened crypt depth.● HS decreased numbers of goblet cells and lymphocytes in intestine.● HS increased mRNA and protein levelss of HSP70, HSP90 and NF-κB, and decreased EGF in jejunal mucosa.
[94] Female growing pigs TN (20°C) vs. HS (35°C during 09:00–17:00 h and 28°C for rest of the day) at 38% RH for 2 days ● HS increased Intestinal HSP70 mRNA abundance.● Increased FITC-d permeability and decreased TER.● Decreased GPx activity.
[22] Arbor Acres male broiler chickens TN (22°C, 24 h/day) and HS (32°C, 10 h/day) for 14 days ● HS decreased villus height in duodenum and ileum but not in jejunum, increased crypt depth and decreased VCR in all intestinal segments.● HS increased MDA content in small intestine.
[62] Crossbred gilts (50 kg BW) TN (21°C, 47% RH) vs. HS (30°C, 35% RH for 10 h/day) for 21 days ● HS decreased ADFI. ADG and final BW, but no effect on feed efficiency.
[135] Male Cobb 500 broilers birds 32°C–27°C vs. 37°C–33°C, decreased 2°C/week until reaching 33°C in third week; for 5 h/day from 29 to 42 day of age ● HS decreased villus length, crypt depth and VCR.● Decreased body weight in HS birds
[78] Crossbred pigs TN (21°C, 35%–50% RH) vs. HS (35°C, 24%–43% RH) for 24 h ● HS decreased feed intake and body weight.● Rectal temperature increased.● HS decreased TER and increased FITC-d permeability in ileum and colon.● HS increased protein expression of casein kinase II α (trend) and MLCK in ileum.● No effect on protein expression of CLDN1, but CLDN3 and OCLN protein up-regulated.● Active glucose and glutamine (trend) transport increased in ileum and glucose level in blood.● HS increased GLUT2 protein expression (trend) and increased Na+/K+-ATPase activity, but no effect on SGLT1 protein abundance in ileum.● HS decreased sucrase and maltase activities, but no effect on ileal mucosal aminopeptidase N activity.● HS increased ileal HIF1A and HSP70 protein expression.● No differences in IL1B and IL8 concentrations, but myeloperoxidase activity increased in ileum.● Protein expression of ileal mast cell tryptase increased.
[72] Crossbred gilts (43 kg BW) TN (20°C, 35%–50% RH) vs. HS (35°C, 20%–35% RH) vs. pair-feeding in TN conditions (PFTN) for 7 days ● HS decreased TER, increased FITC-LPS permeability in jejunum, and increased endotoxin in plasma.● Villus height and VCR decreased linear and quadratic pattern) on day 1, 3, and 7. Crypt depth increased for the first 3 days of HS, and afterward decreased at day 7 compared with day 0 TN.● On day 7, HS tended to increase FITC-LPS permeability compared with PFTN.● Jejunal 4-HNE level (oxidative stress marker) and Na+/K+-ATPase activity increased within first 24 h of HS.● In jejunum, no effect on IL8.● Myeloperoxidase activity (neutrophil infiltration marker) increased in jejunum on day 3 and 7.● Intestinal lysozyme and alkaline phosphatase activity decreased.● Gene expressions of OCLN, CLDN3, and ZO1 increased on day 7 compared with day 0, 1, and 3 of HS.● Jejunal HSP27 up-regulated on day 1 and 3 compared with day 0 and 7. HIF1A level numerically peaked at day 3 of HS and down regulated by day 7.● Gene expression of MLCK in jejunum increased.
[98] Crossbred gilts (63.8 kg BW) TN (21°C, 70% RH for 6 h) vs. HS (37°C, 40% RH for 2, 4, and 6 h) ● HS reduced feed intake and increased rectal temperature.● Ileum TER decreased but no change in colon TER.● Increased ileal FITC-d permeability but not colon FITC-d permeability.● Reduced Ileum villus length and VCR, but not crypt depth.● Increased villi tip autolysis at 4 h and 6 h.● MUC2 protein expression increased at 6 h, but not at 2 and 4 h.● Increased protein expression of HSP70 in ileum and colon. HIF1A protein expression was not affected in ileum, but increased (trend) in colon.● Increased gene expressions of HSP27, HSP70 and HSP90, but no effect on HSF1 expression in ileum.● Increased (linear trend) CLDN3 and MUC2 gene expression in ileum.● No effect on ileal gene expressions of OCLN, MLCK, GLUT2, sodium-glucose transporter 1, Na+/K+-ATPase, TGFB1, IL1β, and IL6.
[136] Crossbred gilts (64 kg BW) TN (21°C, 70% RH) vs. HS (37°C, 40% RH) vs. PFTN condition for 12 h ● HS reduced feed intake and BW in pigs.● HS up-regulated HSP27, HSP90α, HSP90β, HSP70, and HSP65 in ileum.● Peroxiredoxin 1 protein (related to oxidative stress) decreased.● Increased ileal HSP27 and HSP70 gene expression in HS pigs compared with both TN and PFTN pigs.● No effect on ileal HSF1 and HIF1A gene expressions.● Ileal HIF2 tended to increase in HS pigs compared to both TN and PFTN pigs.● No effect on gene expressions of SGLT1, Na+/K+-ATPase, AMP-activated protein kinase-α, GLUT2, citrate synthase, hexokinase, or catalase.
[99] Crossbred gilts (64 kg BW) TN (21°C, 70% RH) vs. HS (37°C, 40% RH) vs. PFTN (pair-feeding to their HS-CON counterparts and exposed to TN conditions) for 12 h ● Reduced feed intake in HS compared with TN.● Ileum villus height and crypt depth decreased in both PFTN and HS.● PFTN and HS increased dextran flux and reduced TER in ileum compared with the TN.● Ileal MUC2 protein abundance increased in HS and PFTN condition.● Colonic TER and dextran flux were similar in HS or PFTN treatments.● HSP70 protein expression increased in ileum of HS compared with the TN and PFTN.● Increased HSP70 protein expression in colon of HS-CON group compared with TN.● Ileum and colonic HIF1A protein expression did not differ.
[59] Broiler chickens TN (21°C) vs. low HS (31°C) vs. high HS (36°C). HS was applied for 10 h/day from 35 days to 42 days ● HS decreased BW gain and ADFI in both HS, but feed conversion ratio increased on high HS.● No effect of HS on villus height, crypt depth, VCR, and intraepithelial lymphocyte numbers in jejunal mucosa.● Cellularity increased in jejunal lamina propria on low HS.● Mild multifocal acute enteritis on HS.● Mild acute multifocal lymphoplasmocytic enteritis found in jejunal lamina propria of low HS.
[65] Male broiler chickens TN (21°C 24 h/day) vs. HS (31°C for 10 h/day and rest 14 h/day at 21°C) ● HS decreased feed intake, BW gain, and feed conversion.● No effect on villus height, crypt depth, VCR, and intraepithelial lymphocyte numbers.● Multifocal lympho-plasmocytic enteritis in jejunum.● Moderate infiltrates with foci of heterophils.
[67] Male broiler chickens TN (21°C, 24 h/day) vs. positive Salmonella TN group (21°C, 24 h/day) vs. positive Salmonella HS group (31°C from 35 to 41 days from 8:00 am to 6:00 pm 10 h/day) vs. negative Salmonella HS group ● HS decreased ADG and ADFI in Salmonella-infected and non-infected birds. HS birds infected with Salmonella Enteritidis exhibited an increased feed conversion.● No effect on VCR, villus height, crypt depth and intraepithelial lymphocyte numbers in any segments of small intestine.● HS without Salmonella infection caused mild acute multifocal lympho-plasmocytic enteritis and foci of heterophil infiltrates in all segments of small intestine, but HS with Salmonella infection increased these changes from mild to moderate.
[137] Cobb 500 male chickens TN (24°C) vs. HS (35°C) with 55 RH from 21 day to 42 days ● HS decreased body weight, feed intake, and feed efficiency on day 28, 35, and 42.● Increased serum FITC-d in HS chickens on day 35 and 42.
[138] 28-day old male broiler chickens TN (25°C) vs. HS (33°C) with 40%–55% RH for 8 h/day) for 10 days ● HS reduced villous height and ileal TER.
[139] Male Cobb 500 broiler chickens TN (26°C) vs. HS (34°C for 8 h daily) for 21 days ● HS decreased feed intake and BW.● HS decreased genes expressions of CLDN3 and OCLN but not CLDN1.● HS increased genes expressions of HSPA1A, HSPD1, and HSPB1.
[140] 17-day-old Ross broiler chickens TN (25°C) vs. HS (39°C) for 8 h/day for 4 days ● HS decreased villus height, epithelial and total villus areas in all small intestine segments.● Decreased villus breadth at the tip and increased crypt depth in jejunum.● VCR decreased in duodenum and ileum.● Increased GPx activity and decreased T-AOC capacity.
[141] Ross-708 chicks of mixed sex Control (35°C at day 1 and decreased 3°C per week to 26°C and then maintained constant) vs. (35°C from day 1 to 42) ● HS decreased BW on day 21 and 42.● HS increased FCR and decreased, feed intake.● HS reduced villus height, width, surface area, and crypt depth on day 21 and 42.
[142] Crossbred gilts (43 kg BW) TN (19°C, 61% RH) vs. HS (36°C, 50% RH) for 1 or 7 days ● HS reduced feed intake and BW gain.● Colonic TER decreased as HS progressed.● Colonic FITC-LPS flux tended to increase from days 1 to 7.
[143] Crossbred gilts (39 kg BW) TN (19°C, 46% RH) vs. HS (32°C, 26% RH ) for 24 h ● Feed intake and body weight decreased.
[7] 21-day-old Ross male broiler chickens TN (22°C, RH 70%) vs. HS (33°C for 10 h/day, RH 70%) from 22–42 days ● Reduced TER value and increased FITC-d permeability in jejunum.● HS caused shorter villus height, deeper crypt depth, and lower VCR in jejunum.● HS downregulated protein levels of OCLN and ZO1.
[1] 15-day-old Ross broilers TN (22°C–23°C) vs. HS (38°C–39°C for 8 h and remaining time at 22°C–23°C) for 5 days ● In jejunum, HSF-3, HSP70, HSP90, CDH1, CLDN5, ZO1, TLR-4, IL6, and IL8 mRNA expression and HSP70 protein expression increased.● Increased all gene expressions in ileum as in jejunum along with HSF1, CLDN1, and HIF1A mRNA levels.
[144] 21-day-old Arbor Acres broiler chickens 36°C for 10 h/day for 20 days ● Decreased villus height, increased crypt depth, D-lactic acid concentration and diamine oxidase activity, and soluble intercellular adhesion molecule-1, TNFA, and IL10 concentrations.● Reduced ZO1, CLDN1, and OCLN expression levels.
[70] Chinese mini pigs TN (23°C) vs. HS (40°C, 5 h/day for 10 days) ● HS reduced VCR.● HS increased the number of shortened internal cristae mitochondria, organelle debris within lysosomes, and altered enterocyte tight junction morphology.● Up-regulated HSP70, HSP90, and HSP27 mRNA expressions, but down-regulated EGF and EGF receptor mRNA expression in jejunum.
[93] Cobb male chickens TN (26°C,) vs. HS (36°C from 08:00 to 18:00 and 26°C from 18:00 to 08:00) ● HS decreased feed intake, BW gain, plasma concentrations of triiodothyronine and thyroxine; increased FCR.● HS decreased intestinal VH, VCR, mucosal ATP level, activities of alkaline phosphatase and digestive enzymes.● HS increased intestinal crypt depth, mucosal AMP and MDA levels, and mRNA levels of HSP70, caspase 3, heme-oxigenase, xanthine oxidoreductase, and AMP-activated protein kinase.
[30] Hy-Line Brown commercial laying hens (40 weeks old) TN (26°C) vs. HS (33°C), with 60%–70% for 20 days ● HS decreased egg production rate, feed intake, and egg weight; increased feed to egg ratio, broken egg ratio, and mortality.● HS caused typical fractures in villi and exposed lamina propria and reduced villus height in ileum and cecum.● Down-regulated expression levels of OCLN, ZO1, and JAM-A in ileum and cecum.
[86] 21-day-old Cobb male broilers TN (22°C) vs HS (33°C) with 70% RH for 10 h and remaining time at 22°C for 21 days ● HS lowered final BW, ADG, and feed intake.● HS decreased villus height, VCR, and goblet cell numbers; deepened crypt depth.● Increased numbers of Escherichia coli, Salmonella, and Clostridium, and lowered Lactobacillus and Bifidobacterium numbers.● Reduced intestinal mucosal CLDN1, OCLN, ZO1, CDH1, and MUC2 mRNA levels.
TN, thermoneutral; HS, heat stress; RH, relative humidity; BW, body weight; ADG, average daily gain; FCR, feed conversion ratio; TNFA, tumour necrosis factor α; IL, interleukin; VCR, villus height to crypt depth ratio; ADFI, average daily feed intake; MDA, malondialdehyde; SOD, superoxide dismutase; CLDN, claudins; MUC, mucin; OCLN, occludin; ZO1, zonula occludens 1; HSP, heat shock protein; TER, transepithelial electrical resistance; FITC-d, fluorescein isothiocyanate–labeled dextran (4.4 kDa); LPS, lipopolysaccharide; PFTN, pair-fed thermal neutral; SGLT1, sodium-dependent glucose cotransporter 1; GPx, glutathione peroxidase; T-AOC, total antioxidant capacity; MLCK, myosin light chain kinase; EGF, epidermal growth factor; NF-κB, nuclear factor kappa B; 4-HNE, 4-hydroxynonenal; TGFB1, transforming growth factor beta 1; CDH1, E-cadherin; HIF1A, hypoxia inducible factor 1α; HSPA1A, heat shock protein family A (HSP70) member 1A; HSPD1, heat shock protein family D (HSP60) member 1, HSPB1, heat shock protein family B (small) member 1; HSF, heat shock factor; GLUT, facilitative glucose transporter; VH, villus height.