Tight junctions (TJs) play an important role in intestinal barrier function. TJs in intestinal epithelial cells are composed of different junctional molecules, such as claudin and occludin, and regulate the paracellular permeability of water, ions, and macromolecules in adjacent cells. One of the most important roles of the TJ structure is to provide a physical barrier to luminal inflammatory molecules. Impaired integrity and structure of the TJ barrier result in a forcible activation of immune cells and chronic inflammation in different tissues. According to recent studies, the intestinal TJ barrier could be regulated, as a potential target, by dietary factors to prevent and reduce different inflammatory disorders, although the precise mechanisms underlying the dietary regulation remain unclear. This review summarizes currently available information on the regulation of the intestinal TJ barrier by food components.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/asj.13357

Regulation of the intestinal barrier by nutrients: The role of tight junctions.

Gut health has significant implications for swine overall health status and nutrient utilization, due to its various functions including digestion and absorption of nutrients, secretion of mucins and immunoglobulins, and selective barrier protection against harmful antigens and pathogens. Both the basic anatomical structure of the gut (such as epithelial cells) and its luminal microbiota play important roles for maintaining gut health and functions. The interactions between epithelial cells and luminal microbiota have significant impact on host nutrition and health through the metabolism of dietary components. Amino acids, which are major nutrients for pigs, are not only obligatory for maintaining the intestinal mucosal mass and integrity, but also for supporting the growth of microorganisms in the gut. Dietary amino acids are the major fuel of the small intestinal mucosa. Particularly, glutamate, glutamine, and aspartate are the major oxidative fuel of the intestine. Emerging evidence shows that arginine activates the mTOR signaling pathway in the small intestine. Utilization of glycine by the small intestinal mucosa to synthesize glutathione is a very important physiological pathway, and the role of glycine as a powerful cytoprotectant has also been recognized. The major end products of methionine and cysteine metabolism are glutathione, homocysteine and taurine, which play important roles in the intestinal immune and anti-oxidative responses. Threonine is highly utilized by the gut and is particularly important for mucin synthesis and maintenance of gut barrier integrity. Moreover, either a deficiency or an excess of dietary threonine can reduce the synthesis of intestinal mucosal proteins and mucins in young pigs. Various new functions of amino acids on gut health and functions have been discovered in recent years. Thus, this review is to provide some up-to-date knowledge for industry application of dietary amino acids in order to enhance swine gut health and functions, and also it is to provide a comprehensive reference for further scientific research in this regard.

/pdf/physiological-effects-of-dietary-amino-acids-on-gut-health-2242qeougs.pdf

Physiological Effects of Dietary Amino Acids on Gut Health and Functions of Swine.

The objective of this study was to evaluate effects of zinc oxide nanoparticles (nano-ZnOs) as a substitute for colistin sulfate (CS) and/or zinc oxide (ZnO) on growth performance, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets. A total of 216 crossbred Duroc×(Landrace×Yorkshire) piglets weaned at 23 days were randomly assigned into 3 groups, which were fed with basal diets supplemented with 20 mg/kg CS (CS group), 20mg/kg CS+3000 mg/kg ZnO (CS+ZnO group), and 1200 mg/kg nano-ZnOs (nano-ZnO group) for 14 days. Results indicated that compared to CS group, supplementation of 1200 mg/kg nano-ZnOs (about 30 nm) significantly increased final body weight and average daily gain, and 3000 mg/kg ZnO plus colistin sulfate significantly increased average daily gain and decreased diarrhea rate in weaned piglets. There was no significant difference in growth performance and diarrhea rate between nano-ZnO and CS+ZnO groups. Supplementation of nano-ZnOs did not affect serum enzymes (glutamic oxalacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase), but significantly increased plasma and tissue zinc concentrations (liver, tibia), improved intestinal morphology (increased duodenal and ileal villus length, crypt depth, and villus surface), enhanced mRNA expression of ZO-1 in ileal mucosa, and significantly decreased diamine oxidase activity in plasma, total aerobic bacterial population in MLN as compared to CS group. Effects of nano-ZnOs on serum enzymes, intestinal morphology, and mRNA expressions of tight junction were similar to those of high dietary ZnO plus colistin sulfate, while nano-ZnOs significantly reduced zinc concentrations of liver, tibia, and feces, and decreased total aerobic bacterial population in MLN as compared to CS+ZnO group. These results suggested that nano-ZnOs (1200 mg/kg) might be used as a substitute for colistin sulfate and high dietary ZnO in weaned piglets.

/pdf/zinc-oxide-nanoparticles-as-a-substitute-for-zinc-oxide-or-4ensafg9yn.pdf

Zinc oxide nanoparticles as a substitute for zinc oxide or colistin sulfate: Effects on growth, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets

The intestinal epithelial layer forms a barrier through cell-cell tight junctions and breaking or even slightly disrupting this barrier can lead to serious pathological consequences, including infection and inflammation. Various amino acids have been shown to improve the intestinal tract, but the effect of tryptophan on the intestinal barrier has been controversial. Here, an in vitro Caco-2 cell model was built to investigate the protective and reparative effects of different concentrations of dietary l-Tryptophan (l-Trp) on lipopolysaccharide (LPS)-induced intestinal tight junction injury. Lower concentrations (40 μM) of dietary l-Trp protected and repaired the integrity and permeability injury of the intestinal tight junction induced by LPS, while high concentrations (80 μM) may not have a positive effect. LPS-induced injury led to increased (P 0.05).

Dietary l-tryptophan alleviated LPS-induced intestinal barrier injury by regulating tight junctions in a Caco-2 cell monolayer model

Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.

/pdf/roles-of-amino-acids-in-preventing-and-treating-intestinal-40dahp2lyp.pdf

Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models

Tryptophan (Trp) plays an essential role in pig behavior and growth performances. However, little is known about Trp's effects on tight junction barrier and intestinal health in weaned pigs. In the present study, twenty-four (24) weaned pigs were randomly assigned to one of the three treatments with 8 piglets/treatments. The piglets were fed different amounts of L-tryptophan (L-Trp) as follows: 0.0%, 0.15, and 0.75%, respectively, named zero Trp (ZTS), low Trp (LTS), and high Trp (HTS), respectively. No significant differences were observed in average daily gain (ADG), average daily feed intake (ADFI), and gain: feed (G/F) ratio between the groups. After 21 days of the feeding trial, results showed that dietary Trp significantly increased (P 0.05) between the groups. Collectively, these data suggest that dietary Trp supplementation at a certain level (0.75%) may negatively affect the small intestinal structure in weaned pig.

/pdf/effect-of-high-dietary-tryptophan-on-intestinal-morphology-31z8nn0nbw.pdf

Tolulope O. Adebowale

Papers

Effect of High Dietary Tryptophan on Intestinal Morphology and Tight Junction Protein of Weaned Pig