Weaning stress and gastrointestinal barrier development: Implications for lifelong gut health in pigs

Abstract

The gastrointestinal (GI) barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions (e.g., digestion, absorption, secretion, immunity, etc.) whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility. Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.

Keywords: Gut health; Intestinal barrier; Mast cells; Pigs; Stress; Weaning.

Fig. 1

Ontogeny of postnatal gastrointestinal (GI) barrier function development in the pig. During the first 12 weeks of postnatal life, the GI system in the pigs undergoes significant development. Colostrum and sow's milk initially provides the piglet protective passive immunity as well as important growth and immune factors. The postnatal period is marked by maturation of the epithelial barrier and transport functions, and immune and enteric nervous systems (indicated by green line) that are almost complete by 12 to 14 weeks of age. Developmental processes occurring this time exhibit a high degree of plasticity and shape the adult phenotype and function of the GI barrier.

Fig. 2

Impact of early weaning on the developmental trajectory of gastrointestinal (GI) barrier function. In nature, weaning is a gradual process occurring at ∼12 to 14 weeks of age, at which time the GI barrier function is near complete. In commercial production systems, weaning is abrupt and compounded by multiple social and environmental stressors and occurs at the height of GI barrier development between 2 and 4 weeks of age. Early weaning pigs exhibit an altered GI barrier developmental trajectory (red dashed line) resulting in permanent, suboptimal barrier function and increased disease susceptibility.

Fig. 3

Mechanisms of intestinal barrier dysfunction induced by production stressors in pigs: corticotropin releasing factor (CRF)-mast cell axis. Production stressors such as weaning, mixing/crowding and gastrointestinal (GI) infections, trigger activation of intestinal CRF and receptors. The CRF receptor activation enhances intestinal mast cell activation and hyperplasia and the release of mast cell mediators including proteases (e.g., tryptase and chymase) and tumor necrosis factor-α (TNF-α). Mast cell proteases and TNF-α induce increases in intestinal epithelial permeability.