Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na⁺/K⁺ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.

Heat stress can compromise intestinal integrity and induce leaky gut in a variety of species. Therefore, the objectives of this study were to determine if heat stress (HS) directly or indirectly (via reduced feed intake) increases intestinal permeability in growing pigs. We hypothesized that an increased heat-load causes physiological alterations to the intestinal epithelium, resulting in compromised barrier integrity and altered intestinal function that contributes to the overall severity of HS-related illness. Crossbred gilts (n = 48, 43 ± 4 kg BW) were housed in constant climate controlled rooms in individual pens and exposed to 1) thermal neutral (TN) conditions (20°C, 35–50% humidity) with ad libitum intake, 2) HS conditions (35°C, 20–35% humidity) with ad libitum feed intake, or 3) pair-fed in TN conditions (PFTN) to eliminate confounding effects of dissimilar feed intake. Pigs were sacrificed at 1, 3, or 7 d of environmental exposure and jejunum samples were mounted into modified Ussing chambers for assessment of transepithelial electrical resistance (TER) and intestinal fluorescein isothiocyanate (FITC)-labeled lipopolysaccharide (LPS) permeability (expressed as apparent permeability coefficient, APP). Further, gene and protein markers of intestinal integrity and stress were assessed. Irrespective of d of HS exposure, plasma endotoxin levels increased 45% (P < 0.05) in HS compared with TN pigs, while jejunum TER decreased 30% (P < 0.05) and LPS APP increased 2-fold (P < 0.01). Furthermore, d 7 HS pigs tended (P = 0.06) to have increased LPS APP (41%) compared with PFTN controls. Lysozyme and alkaline phosphatase activity decreased (46 and 59%, respectively; P < 0.05) over time in HS pigs, while the immune cell marker, myeloperoxidase activity, was increased (P < 0.05) in the jejunum at d 3 and 7. These results indicate that both HS and reduced feed intake decrease intestinal integrity and increase endotoxin permeability. We hypothesize that these events may lead to increased inflammation, which might contribute to reduced pig performance during warm summer months. Copyright © 2013. American Society of Animal Science .

Acute heat stress (HS) and heat stroke can be detrimental to the health, well-being, and performance of mammals such as swine. Therefore, our objective was to chronologically characterize how a growing pig perceives and initially copes with a severe heat load. Crossbred gilts (n = 32; 63.8 ± 2.9 kg) were subjected to HS conditions (37°C and 40% humidity) with ad libitum intake for 0, 2, 4, or 6 h (n = 8/time point). Rectal temperature (T_r), respiration rates (RR), and feed intake were determined every 2 h. Pigs were euthanized at each time point and fresh ileum and colon samples were mounted into modified Ussing chambers to assess ex vivo intestinal integrity and function. Transepithelial electrical resistance (TER) and fluorescein isothiocyanate–labeled dextran (FD4) permeability were assessed. As expected, T_r increased linearly over time (P < 0.001) with the highest temperature observed at 6 h of HS. Compared to the 0-h thermal-neutral (TN) pigs, RR increased (230%; P < 0.001) in the first 2 h and remained elevated over the 6 h of HS (P < 0.05). Feed intake was dramatically reduced due to HS and this corresponded with significant changes in plasma glucose, ghrelin, and glucose-dependent insulinotropic peptide (P < 0.050). At as early as 2 h of HS, ileum TER linearly decreased (P < 0.01), while FD4 linearly increased with time (P < 0.05). Colon TER and FD4 changed due to HS in quadratic responses over time (P = 0.050) similar to the ileum but were less pronounced. In response to HS, ileum and colon heat shock protein (HSP) 70 mRNA and protein abundance increased linearly over time (P < 0.050). Altogether, these data indicated that a short duration of HS (2–6 h) compromised feed intake and intestinal integrity in growing pigs. Copyright © 2014. American Society of Animal Science .

Endotoxin, also referred to as lipopolysaccharide (LPS), can stimulate localized or systemic inflammation via the activation of pattern recognition receptors. Additionally, endotoxin and inflammation can regulate intestinal epithelial function by altering integrity, nutrient transport, and utilization. The gastrointestinal tract is a large reservoir of both gram-positive and gram-negative bacteria, of which the gram-negative bacteria serve as a source of endotoxin. Luminal endotoxin can enter circulation via two routes: 1) nonspecific paracellular transport through epithelial cell tight junctions, and 2) transcellular transport through lipid raft membrane domains involving receptor-mediated endocytosis. Paracellular transport of endotoxin occurs through dissociation of tight junction protein complexes resulting in reduced intestinal barrier integrity, which can be a result of enteric disease, inflammation, or environmental and metabolic stress. Transcellular transport, via specialized membrane regions rich in glycolipids, sphingolipids, cholesterol, and saturated fatty acids, is a result of raft recruitment of endotoxin-related signaling proteins leading to endotoxin signaling and endocytosis. Both transport routes and sensitivity to endotoxin may be altered by diet and environmental and metabolic stresses. Intestinal-derived endotoxin and inflammation result in suppressed appetite, activation of the immune system, and partitioning of energy and nutrients away from growth toward supporting the immune system requirements. In livestock, this leads to the suppression of growth, particularly suppression of lean tissue accretion. In this paper, we summarize the evidence that intestinal transport of endotoxin and the subsequent inflammation leads to decrease in the production performance of agricultural animals and we present an overview of endotoxin detoxification mechanisms in livestock. Copyright © 2012. American Society of Animal Science .

Dietary zinc (inorganic and organic or zinc AA complex forms) is essential for normal intestinal barrier function and regeneration of intestinal epithelium. Given that heat stress (HS) exposure can negatively affect intestinal integrity and caloric intake, possible nutritional mitigation strategies are needed to improve health, performance, and well-being. Therefore, our objective was to evaluate 2 dietary zinc sources and reduced caloric intake on intestinal integrity in growing pigs subjected to 12 h of HS. A total of 36 pigs were fed 1 of 2 diets: 1) a control diet (CON; 120 mg/kg of zinc from zinc sulfate) or 2) 60 mg/kg from zinc sulfate and 60 mg/kg from zinc AA complex (ZnAA). After 17 d, the CON pigs were then exposed to thermal neutral (TN) conditions with ad libitum intake (TN-CON), HS (37°C) with ad libitum intake (HS-CON), or pair-fed to HS intake under TN conditions (PFTN); the ZnAA pigs were exposed to only HS (HS-ZnAA). All pigs were sacrificed after 12 h of environmental exposure, and blood and tissue bioenergetics stress markers and ex vivo ileum and colon integrity were assessed. Compared with TN-CON, HS significantly (P < 0.05) increased rectal temperatures and respiration rates. Ileum villus and crypt morphology was reduced by both pair-feeding and HS. Both PFTN and HS-CON pigs also had reduced ileum integrity (dextran flux and transepithelial resistance) compared with the TN-CON pigs. However, ZnAA tended to mitigate the HS-induced changes in ileum integrity. Ileum mucin 2 protein abundance was increased due to HS and pair-feeding. Colonic integrity did not differ due to HS or PFTN treatments. Compared with the HS-CON, HS-ZnAA pigs tended to have reduced blood endotoxin concentrations. In conclusion, HS and reduced feed intake compromised intestinal integrity in pigs, and zinc AA complex source mitigates some of these negative effects.

Background: Intestinal derived endotoxin and the subsequent endotoxemia can be considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes. Dietary fat has been shown to increase postprandial endotoxemia. Therefore, the aim of this study was to assess the effects of different dietary oils on intestinal endotoxin transport and postprandial endotoxemia using swine as a model. We hypothesized that oils rich in saturated fatty acids (SFA) would augment, while oils rich in n-3 polyunsaturated fatty acids (PUFA) would attenuate intestinal endotoxin transport and circulating concentrations.Methods: Postprandial endotoxemia was measured in twenty four pigs following a porridge meal made with either water (Control), fish oil (FO), vegetable oil (VO) or coconut oil (CO). Blood was collected at 0, 1, 2, 3 and 5 hours postprandial and measured for endotoxin. Furthermore, ex vivo ileum endotoxin transport was assessed using modified Ussing chambers and intestines were treated with either no oil or 12.5% (v/v) VO, FO, cod liver oil (CLO), CO or olive oil (OO). Ex vivo mucosal to serosal endotoxin transport permeability (Papp) was then measured by the addition of fluorescent labeled-lipopolysaccharide.Results: Postprandial serum endotoxin concentrations were increased after a meal rich in saturated fatty acids and decreased with higher n-3 PUFA intake. Compared to the no oil control, fish oil and CLO which are rich in n-3 fatty acids reduced ex vivo endotoxin Papp by 50% (P < 0.05). Contrarily, saturated fatty acids increased the Papp by 60% (P = 0.008). Olive and vegetable oils did not alter intestinal endotoxin Papp.Conclusion: Overall, these results indicate that saturated and n-3 PUFA differentially regulate intestinal epithelial endotoxin transport. This may be associated with fatty acid regulation of intestinal membrane lipid raft mediated permeability.