Understanding the influences of early life adversity on intestinal epithelial development and functions in pigs

    

Developmental plasticity during the prenatal and early postnatal periods allows animals to adapt quickly to their environment and efficiently construct organ systems crucial for survival. These adaptations, which may be irreversible later in life, can lead animals to develop beneficial survival strategies or predispose them to chronic diseases. The gastrointestinal (GI) tract is a highly adaptive organ, contending with the continuous changes in the complex luminal environment. It senses and selectively absorbs nutrients while blocking harmful antigens and pathogens. Optimal intestinal functions largely depend on the renewal and maturation of epithelial cell populations, which are actively produced by intestinal epithelial stem cells (IESC). Considering the rapid turnover rate of epithelial cells (every 3 to 5 d), any long-lasting alterations in epithelial functions could potentially stem from intrinsic changes in IESC. During early development, the relatively high number and activity of stem cells enable efficient adaptation to environmental challenges. The impact of early life stress on IESC activities and epithelial cell populations remains largely unexplored. We used the unique Ussing chamber electrophysiological technique and cutting-edge enteroid culture technique to assess intestinal stem cell activities and epithelial cell composition, as well as intestinal barrier, nutrient sensing, and transport functions both immediately and long-term postearly weaning stress in pigs. Overall, our findings suggest that early weaning stress disrupts intestinal development and function, partly due to alterations in IESC proliferation and differentiation activities. The stress signals contributed to long-term changes in the number and function of epithelial absorptive and secretory cell populations, enhancing survival efficiency. Understanding IESC regulation during early life development can pave the way for identifying novel strategies to ensure optimal gut health and regeneration under stress.

Key Words: Pigs, stress, stem cell, nutrient transport, enteroids.