Browsing by Author "Yu, Liang-en"
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Item Characterizing the effects of early life adversity on intestinal epithelial development and functions in swine and poultry models(University of Delaware, 2023) Yu, Liang-enDevelopmental plasticity during the prenatal and early postnatal periods of life significantly contributes to animals’ organ development and functions. In such a sensitive window, the animals quickly sense and adapt to the surrounding environment, efficiently building up organ machinery that is suitable for survival. These adaptations may be irreversible throughout the later life, and either lead animals to beneficial strategies for survival or predispose animals to a detrimental risk of disease. The gastrointestinal (GI) tract is a highly adaptive organ dealing with the constant changes of the complicated luminal environment. It senses and absorbs nutrients while selectively blocking the intrusion of harmful antigens and pathogens for animals. However, whether and how early life events affect later life intestinal function is not fully studied in agricultural animals. ☐ Optimal intestinal epithelial functions are largely contributed by the renewal and maturation of epithelial cell populations (such as enterocytes, goblet cells, Paneth cells, and enteroendocrine cells), which are actively generated by intestinal epithelial stem cells (IESC). Given the rapid turnover rate of epithelial cells (every 3~5 days), any long-lasting alterations in epithelial functions could be potentially originated from intrinsic alternations in IESCs. During early development, the relatively high number and activity of stem cells allows more efficient adaptation to the environment challenges than later life. This sets up an intestinal machinery that supports long term survival. Whether early life events influence IESC activities and epithelial cell populations is largely unknown. ☐ In this dissertation, we utilized broiler chickens and pigs as animal models to identify effects of 3 early life events on intestinal development and functions, including 1) 72h delayed post-hatch feeding stress (DF) in chickens, 2) in-ovo nutritional intervention in chickens, and 3) early weaning stress (EW) in pigs. We applied the unique Ussing chamber electrophysiological technique and cutting-edge enteroids culture technique to identify intestinal stem cell activities, epithelial cell population, barrier function, nutrient sensing and transport functions at acute and long-term stage post early life events. Our results showed that both DF and EW decreased villi surface area and intestinal barrier function. Interestingly, the relocation of enteroendocrine cells (EEC) was found in ileum tissue, which paralleled with the decreasing of nutrient sensing function and serum glucagon-like peptide 2 (GLP2) concentration. The decreasing of enteroid formation rate, size, and expansion in basolateral-out enteroids, which indicated the activity of IESC was decreased dramatically in both DF chickens and EW pigs. Moreover, the differentiation ability of IESC into enterocytes and EEC decreased in EW pigs’ enteroids. On the other hand, in-ovo Gln injection increased intestinal growth, development and functional maturation, which indicated the early life nutrient intervention is suitable for improving intestinal development. Further, we demonstrated the novel intestinal functional analysis for gut permeability, glucose absorption, and proliferation. ☐ Overall, we found the similarity in gut development between the mammalians and non-mammal oviparous animals. The early life events interferences intestinal development and functions via alterations of IESC’s proliferation and differentiation activities. The added nutrients and stress signals both contributed to the long-term changes in the number and function of epithelial absorptive and secretory cell populations, which increased the survival efficiency. Understanding IESC regulation during early life development will shed light on identifying novel strategies for optimal gut health and regeneration under stress.Item Effects of microencapsulated blend of organic acids and botanicals on growth performance, intestinal barrier function, inflammatory cytokines, and endocannabinoid system gene expression in broiler chickens(Poultry Science, 2023-01-20) Bialkowski, Sofia Bialkow; Toschi, Andrea; Yu, Liang-en; Schlitzkus, Lydia; Mann, Peter; Grilli, Ester; Li, YihangWith restricted usage of growth-promoting antibiotics, identifying alternative feed additives that both improve intestinal barrier function and reduce inflammation is the center to improve chickens’ health. This study examined the effects of a microencapsulated feed additive containing citric acid, sorbic acids, thymol, and vanillin on intestinal barrier function and inflammation status. A total of 240 birds were assigned to either a commercial control diet or control diet supplemented with 500 g/MT of the microencapsulated additive product. Birds were raised by feeding a 2-phase diet (starter, d 1 to d 21; and grower, d 15 to d 42). Growth performance was recorded weekly. At d 21 and d 42, total gastrointestinal tract permeability was evaluated by FITC-dextran (FD4) oral gavage. Jejunum-specific barrier functions were evaluated by Ussing chamber. Intestinal gene expression of selected epithelial cell markers, tight junction (TJ) proteins, inflammatory cytokines, and endocannabinoid system (ECS) markers were determined by RT-PCR. Statistical analysis was performed using Student t test. Results showed significant improvement of feed efficiency in the birds supplemented with the blend of organic acids and botanicals. At d 21, both oral and jejunal FD4 permeability were lower in the supplemented group. Jejunal transepithelial resistance was higher in the supplemented birds. At d 21, expression of TJs mRNA (CLDN1 and ZO2) was both upregulated in the jejunum and ileum of supplemented birds, while CLDN2 was downregulated in cecum. Proliferating cell marker SOX9 was higher expressed in jejunum and ceca. Goblet cell marker (MUC2) was upregulated, while Paneth cell marker (LYZ) was downregulated in the ileum. Proinflammatory cytokine expressions of IL1B, TNFA, and IFNG were downregulated in jejunum, while anti-inflammatory IL10 expression was higher in jejunum, ileum, cecum, and cecal tonsil. The ECS markers expressions were upregulated in most intestinal regions. Together, these results demonstrated that the blend of organic acids and botanical supplementation reduced inflammation, improved the TJs expression and intestinal barrier function, and thus improved chicken feed efficiency. The activated ECS may play a role in reducing intestinal tissue inflammation.Item In-Ovo Glutamine Administration Enhances Intestinal Development and Functions in Broiler Chickens: Insights from Enteroid Models(The Journal of Nutrition, 2024-04-10) Yu, Liang-en; Mann, Peter; Schlitzkus, Lydia; Ghiselli, Federico; Sanders, Mia; Hadimundeen, Abdallah; Li, YihangBackground Early life events play significant roles in tissue development and animal health in their later life. Early nutrition, through in-ovo delivery, has shown beneficial effects on improving intestinal health in broiler chickens. However, the underlying mechanism is not fully investigated. A recently developed enteroid culture technique allows investigations on intestinal epithelial functions that are close to physiologic conditions. Objectives In this study, we evaluated the short- and long-term effects of in-ovo administration of glutamine (Gln) on intestinal epithelial development and functions by using intestinal enteroid culture and tissue electrophysiologic analysis. Methods A hundred eggs of commercial Cobb500 broilers were in-ovo injected with 0.2 mL of either phosphate-buffered saline (PBS) or 3% Gln at embryonic day 18 (E18). Chicks were killed on the day of hatch, and at 3- and 14-d posthatch. Enteroids were generated from the small intestine. After 4 d of culture, enteroids were harvested for 5-ethynyl-2′-deoxyuridine proliferation, fluorescein isothiocyanate-4 kDa dextran permeability, and glucose absorption assays. At day 3 (d3) and day 14 (d14), intestinal barrier and nutrient transport functions were measured by the Ussing chamber. The gene expression of epithelial cell markers, nutrient transporters, and tight-junction proteins were analyzed in both intestinal tissues and enteroids. Results In comparison with the PBS control group, in-ovo Gln increased intestinal villus morphology, epithelial cell proliferation, and differentiation, and altered epithelial cell population toward increased number of enteroendocrine and goblet cells while decreasing Paneth cells. Enteroids gene expression of nutrient transporters (B0AT1, SGLT1, and EAAT3), tight junction (ZO2), glucose absorption, and barrier functions were enhanced on the day of hatch. Long-term increases of intestinal di-peptide and alanine transport were observed at day 14 posthatch. Conclusions Together our results suggested that the in-ovo injection of Gln stimulated intestinal epithelium proliferation and programmed the epithelial cell differentiation toward absorptive cells.