The gastrointestinal tract presents the largest and most vulnerable surface to the outside world. Simultaneously, it must be accessible and permeable to nutrients and must defend against pathogens and potentially injurious chemicals. Integrated responses to these challenges require the gut to sense its environment, which it does through a range of detection systems for specific chemical entities, pathogenic organisms and their products (including toxins), as well as physicochemical properties of its contents. Sensory information is then communicated to four major effector systems: the enteroendocrine hormonal signalling system; the innervation of the gut, both intrinsic and extrinsic; the gut immune system; and the local tissue defence system. Extensive endocrine-neuro-immune-organ-defence interactions are demonstrable, but under-investigated. A major challenge is to develop a comprehensive understanding of the integrated responses of the gut to the sensory information it receives. A major therapeutic opportunity exists to develop agents that target the receptors facing the gut lumen.

A study was conducted to evaluate the effects of 3 different plant extracts on diarrhea, immune response, intestinal morphology, and growth performance of weaned pigs experimentally infected with a pathogenic F-18 Escherichia coli (E. coli). Sixty-four weaned pigs (6.3±0.2 kg BW, and 21 d old) were housed in individual pens in disease containment chambers for 15 d: 4 d before and 11 d after the first inoculation (d 0). Treatments were in a 2×4 factorial arrangement: with or without an F-18 E. coli challenge (toxins: heat-labile toxin, heat-stable toxin b, and Shiga-like toxin 2; 10(10) cfu/3 mL oral dose; daily for 3 d from d 0) and 4 diets [a nursery basal diet (CON) or 10 ppm of capsicum oleoresin, garlic botanical, or turmeric oleoresin]. The growth performance was measured on d 0 to 5, 5 to 11, and 0 to 11. Diarrhea score (1, normal, to 5, watery diarrhea) was recorded for each pig daily. Frequency of diarrhea was the percentage of pig days with a diarrhea score of 3 or greater. Blood was collected on d 0, 5, and 11 to measure total and differential white blood cell counts and serum tumor necrosis factor (TNF)-α, IL-10, transforming growth factor (TGF)-β, C-reactive protein, and haptoglobin. On d 5 and 11, half of the pigs were euthanized to measure villi height and crypt depth of the small intestine and macrophage and neutrophil number in the ileum. The E. coli infection increased (P<0.05) diarrhea score, frequency of diarrhea, white blood cell counts, serum TNF-α and haptoglobin, and ileal macrophages and neutrophils but reduced (P<0.05) villi height and the ratio of villi height to crypt depth of the small intestine on d 5. In the challenged group, feeding plant extracts reduced (P<0.05) average diarrhea score from d 0 to 2 and d 6 to 11 and frequency of diarrhea and decreased (P<0.05) TNF-α and haptoglobin on d 5, white blood cell counts and neutrophils on d 11, and ileal macrophages and neutrophils on d 5. Feeding plant extracts increased (P<0.05) ileal villi height on d 5 but did not affect growth performance compared with the CON. In the sham group, feeding plant extract also reduced (P<0.05) diarrhea score, frequency of diarrhea, and ileal macrophages compared with the CON. In conclusion, the 3 plant extracts tested reduced diarrhea and inflammation caused by E. coli infection, which may be beneficial to pig health.

New Findings r What is the central question of this study?Oxidative stress may play a role in compromising intestinal epithelial barrier integrity in pigs subjected to heat stress, but it is unknown whether an increase of dietary antioxidants (selenium and vitamin E) could alleviate gut leakiness in heat-stressed pigs. r What is the main finding and its importance? Levels of dietary selenium (1.0 p.p.m.) and vitamin E (200 IU kg −1 ) greater than those usually recommended for pigs reduced intestinal leakiness caused by heat stress. This finding suggests that oxidative stress plays a role in compromising intestinal epithelial barrier integrity in heat-stressed pigs and also provides a nutritional strategy for mitigating these effects.Heat stress compromises the intestinal epithelial barrier integrity of mammals through mechanisms that may include oxidative stress. Our objective was to test whether dietary supplementation with antioxidants, selenium (Se) and vitamin E (VE), protects intestinal epithelial barrier integrity in heat-stressed pigs. Female growing pigs (n = 48) were randomly assigned to four diets containing from 0.2 p.p.m. Se and 17 IU kg −1 VE (control, National Research Council recommended) to 1.0 p.p.m. Se and 200 IU kg −1 VE for 14 days. Six pigs from each dietary treatment were then exposed to either thermoneutral (20°C) or heat-stress conditions (35°C 09.00-17.00 h and 28°C overnight) for 2 days. Transepithelial electrical resistance and fluorescein isothiocyanate-dextran (4 kDa; FD4) permeability were measured in isolated jejunum and ileum using Ussing chambers. Rectal temperature, respiratory rate and intestinal HSP70 mRNA abundance increased (all P < 0.001), and respiratory alkalosis occurred, suggesting that pigs were heat stressed. Heat stress also increased FD4 permeability and decreased transepithelial electrical resistance (both P < 0.01). These changes were associated with changes indicative of oxidative stress, a decreased glutathione peroxidase (GPX) activity and an increased glutathione disulfide (GSSG)-to-glutathione (GSH) ratio (both P < 0.05). With increasing dosage of Se and VE, GPX-2 mRNA (P = 0.003) and GPX activity (P = 0.049) F. Liu and others increased linearly, the GSSG:GSH ratio decreased linearly (P = 0.037), and the impacts of heat stress on intestinal barrier function were reduced (P < 0.05 for both transepithelial electrical resistance and FD4 permeability). In conclusion, in pigs an increase of dietary Se and VE mitigated the impacts of heat stress on intestinal barrier integrity, associated with a reduction in oxidative stress.

In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na þ /glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L-and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

Plant extracts, or phytonutrients, are used in traditional medicine practices as supplements to enhance the immune system and gain resistance to various infectious diseases and are used in animal production as health promoting feed additives. To date, there are no studies that have assessed their mechanism of action and ability to alter mucosal immune responses in the intestine. We characterized the immunomodulatory function of six phytonutrients: anethol, carvacrol, cinnamaldehyde, eugenol, capsicum oleoresin and garlic extract. Mice were treated with each phytonutrient to assess changes to colonic gene expression and mucus production. All six phytonutrients showed variable changes in expression of innate immune genes in the colon. However only eugenol stimulated production of the inner mucus layer, a key mucosal barrier to microbes. The mechanism by which eugenol causes mucus layer thickening likely involves microbial stimulation as analysis of the intestinal microbiota composition showed eugenol treatment led to an increase in abundance of specific families within the Clostridiales order. Further, eugenol treatment confers colonization resistance to the enteric pathogen Citrobacter rodentium. These results suggest that eugenol acts to strengthen the mucosal barrier by increasing the thickness of the inner mucus layer, which protects against invading pathogens and disease.