<p>In sum, these studies described in this dissertation showed that both mycotoxin deoxynivalenol exposure and nutrient starvation can increase endocytosis and degradation of tight junction proteins in the lysosome. Therefore, manipulation of endocytic pathway as well as the signaling pathway involved in this process can be used to prevent intestinal barrier dysfunction in animals.</p> <p><br></p>

The use of computed tomography in patients with gastrointestinal disease is increasing. However, the triple-phase computed tomographic angiographic appearance of the canine small intestine and the effects that phase of contrast enhancement and plane of reconstruction have on the appearance of the small intestine have not been fully evaluated. The purposes of this study were to investigate these effects on the appearance of the small intestinal wall. The minimal and maximal small intestinal diameter, wall thickness, number of wall layers identified, and degree of mucosal enhancement were recorded. The plane of reconstruction did not have any significant effects on wall thickness, diameter, degree of mucosal enhancement, or number of wall layers identified. There was a positive association between body weight and intestinal diameter. The arterial phase demonstrated the greatest mucosal enhancement and number of wall layers identified. The transverse plane was subjectively the most useful for evaluation of the small intestines.

Studies investigating the effect of 5-HT receptors mediating a response in the neonatal intestine have been limited. There are evidences that the development of new neurones continues past postnatal term and this suggests that receptors expression may differ during maturation. Thus, `in vitro¿ experiments were carried out to investigate the effects of ACh, atropine, 5-HT and its related drugs on intact intestinal segments taken from the ileum of adult and neonate rats. The application of ACh (3nM-1mM) and 5-HT (3nM-1mM) induced contractions in a concentration dependent manner in all tissues examined. The 5-HT induced contractions were only sensitive to antagonism by atropine (1¿M) in segments taken from the neonates but not adults. The pre-treatment with methysergide (5-HT1/2/5-7 receptor antagonist), ritanserin (5-HT2 receptor antagonist), granisetron (5-HT3 receptor antagonist) and RS 23597 (5-HT4 receptor antagonist) at 1¿M or a combination of ritanserin, granisetron, plus RS 23597 at 1¿M significantly reduced or abolished contractile responses induced by 5-HT. SB 269970A (5-HT7 receptor antagonist) and WAY 100635 (5-HT1A receptor antagonist) at 1¿M failed to influence contractile responses induced by 5-HT or the challenges to 5-HT receptor agonists, 5-CT (5-HT1A/7 receptor agonist) and 8-OH-DPAT (5-HT1A receptor agonist) at a concentration range of 10nM-0.1mM, indicating the unlikely involvement of 5-HT1A and 5-HT7 receptors in the mediation of contractile responses in the neonatal rat ileum. Results indicate differences in cholinergic receptor involvement during postnatal maturation and suggest the involvement of 5-HT2, 5-HT3 and 5-HT4 receptors in the mediation of contractile responses to 5-HT in the neonatal rat ileum. There is a growing need to decrease animal usage in pharmacological experiments. This may be achieved by the development of `in vitro¿ cell culture models. Thus attempts were also made to develop a cell culture model of neonatal intestine to further investigate the action of pharmacologically active agents. The isolation of individual cell populations from segments taken from the intestine of rat neonates were achieved by ligation of both ends of the intestine prior to incubation in trypsin so that a gradual dissociation could be monitored. This was supported by histological procedures, determining the time required to extract large numbers of cells from different intestinal layers. Differential adhesion and selective cytotoxicity techniques were used for further purification of intestinal smooth muscle cells (ISMC), neuronal cells, and a coculture of ISMC and neuronal cells, and these were characterised through immunostaining with antibodies to ¿-smooth muscle actin, ¿-actinin and the 5-HT3 receptor. A protocol for cryopreservation of ISMC was designed in order to protect cells against genetic instability, enhance cell availability and reduce animal usage. Results showed that cells extracted from the intestine are viable for up to 4-months. ISMC functionality was analysed via the application of known pharmacologically active drugs on ISMC, which were plated onto glass and silicone elastomer substrate. The cultured ISMC responded to the application of drugs such as potassium chloride (KCl), carbachol, 5-HT and noradrenaline (NA). Large population of cocultures seeded onto silicone elastomers or cholesteric liquid crystal substrates (LC) were assessed for their ability to produce a collective response to KCl application. Attempts were made to detect any deformations of the substrate surface due to the exposure to KCl and NA. Cholesteric LC substrates seemed to be the most suitable material for investigating the cellular tensions. The availability of cell cultures allowed the development of an intestinal model of inflammation. This was achieved through the use of lipopolysaccharide (LPS)-induced inflammation and was confirmed by assessing the levels pro-inflammatory mediators interleukin (IL-8) and nitric oxide (NO), which were significantly elevated. Reduction of IL-8 ad NO was also examined using granisetron and L-NAME and Chaga mushroom extract. Granisetron and L-NAME reduced the NO production during short incubation times. However, an elevated level of NO was observed when longer treatment times were examined. The Chaga mushroom extract caused a significant reduction in NO production in the model of inflammation. This indicates that this model may be a valuable tool for the investigation of other pro-inflammatory mediators and may contribute for the investigation of more selective drugs in the management of intestinal inflammation in neonates.

The global pandemic of diet-related non-communicable diseases and the fact that global food production represents one of the largest contributors to greenhouse gas emissions, have identified unhealthy and unsustainably food chains as a major societal health challenge and a risk to ecosystem stability. This thesis aimed to investigate if digestion of nutritious, less highly processed foods could lead to health-promoting changes in the gut microbiota. Our modern Western-style diet (MWD) is characterized by high intake of extremely processed foods, which contain significant concentrations of inflammatory advanced glycation end-products (AGE) implicated in metabolic disease development. Novel observations in this thesis showed that chronic exposure to dietary AGE modulated gut microbiota (GM) community structure rendering it more similar to the GM previously observed in diabetic/obese mice. Further, I demonstrated that elevated systemic inflammatory markers could be mediated by AGE induced changes in GM composition. Measuring the potential of whole plant foods to improve gut health, a local broccoli ecotype (Broccolo of Torbole, BR) and Moringa oleifera were investigated using in vitro models of the human GM and intestinal epithelium. BR significantly reduced bacterial richness and evenness, increased Escherichia-Shigella relative abundance and decreased Alistipes and Ruminococcus 1. The GM extensively metabolized BR polyphenols and increased concentrations of short chain fatty acids. However, BR did not impact on intestinal permeability, using a Caco-2 monolayer model and trans-epithelial electrical resistance (TEER). This thesis provided novel insights on the fate of Moringa glucosinolates and polyphenols during faecal fermentation and on their potential beneficial activity on gut health, with glucomoringin significantly increasing TEER. Microbial communities are also involved in healthy and sustainable food production. Characterizing the successional development of local organic sauerkraut production, this thesis established a culture collection of sauerkraut lactic acid bacteria of potential future biotechnological evaluation and measured metabolite production during sauerkraut fermentation. Sauerkraut water improved immune response of a Caco-2-peripheral blood mononuclear cell (PBMC) in vitro model of the gut associated immune system upon inflammatory LPS challenge. Finally, since sustainable diets rely on sustainable and nutritious foods, I analyzed the role of the GM in improving the sustainability of farmed trout. Novel sustainable feeds containing poultry by-products (P) or insect protein (Hermetia illucens (H) meal), were investigated for their potential impact on fish growth performance, GM composition and inflammatory biomarkers. P increased the relative abundance of protein-degraders Paeniclostridium and Bacteroidales, while H increased chitin-degraders Actinomyces and Bacillus. This study also provided evidence of feed-chain microbiome transmission of Actinomyces from insect H feed to trout GM. The analysis of gut microbiomes therefore represents an innovative strategy to define healthy reference diets, to characterize the potential health effects of local and traditionally produced foods, to identify new sustainable and nutritious crops, and to drive the urgently needed transformation of the global food system. In order to obtain more sustainable, healthy and nutritious food production systems a better understanding and management of microbiomes along the food chain has never been more important.

The F-strain of Mycoplasma gallisepticum (FMG) is commonly used in vaccination programs to displace infections by more virulent natural or wild type Mycoplasma gallisepticum strains. However, a better understanding of the mechanisms responsible for altered egg production (EP) and egg quality in commercial layers infected with FMG is important, as these alterations can cause economic loss to the United States layer industry. This study was designed to examine potential mechanism(s) responsible for alterations in EP and egg quality by FMG-inoculation. The effects of FMG on production parameters and physiological characteristics of commercial laying hens were evaluated. In isolation units, 12 wk FMG inoculation delayed onset of lay approximately one wk, decreased overall EP, and decreased EP 34 wk post-inoculation. A 12 wk FMG inoculation also resulted in a higher incidence of fatty liver hemorrhagic syndrome, ovarian follicular regression, and decreased isthmal and vaginal proportions of the reproductive tract. Ovarian regression may be related to retarded production (liver), transport (blood), and/or uptake (ovary) of yolk particles. Changes in blood characteristics (i.e. lipid composition) with FMG colonization of the liver may become manifest through changes in egg constituents. As evidenced through changes in the relative weights of various reproductive organs, colonization of these organs by FMG, in addition to the liver, may also be a cause of the effects observed on EP. Increases in hematocrit, serum triglycerides, and plasma protein between 8 and 10 wk post FMG-inoculation, suggest that the initial weeks of EP are stressful. Post-peak decreases in these same variables suggest a more chronic inhibition on lipid and protein synthesis in the liver. Decreased blood lipid concentration may be directly responsible for the reductions in yolk lipid, cholesterol, and fatty acid deposition in 12 wk FMG-inoculated hens. Dual adverse effects in the caged layer facility on feed conversion and egg mass were realized in 22 wk FMG-inoculated birds. In contrast, a 12 wk FMG inoculation delayed onset of lay without a loss in total EP or egg mass. Therefore, inoculation with FMG at 12 wk is more practical and cost effective. Higher degrees of physiological stress experienced by hens in a caged layer facility may exacerbate the effects of FMG inoculation seen in the isolation units. These data demonstrate that alterations in performance and egg characteristics of commercial layers inoculated with FMG at either 12 or 22 wk of age and housed in either isolation units or caged layer facilities are related to mutual functional disturbances in the blood, liver, ovary, and oviduct without concomitant intestinal changes.

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