Induced Growth and Precocious Maturation of the Digestive System in Suckling Rats and Pigs after Exposure to Red Kidney Bean Lectin

Sammanfattning: The timing of the postnatal development of the gastrointestinal (GI) tract in mammals is influenced by dietary and hormonal factors. It was hypothesized that accelerated GI cell turnover during maturation would result in a precoucios conversion to more mature digestive functions. Thus, it was investigated if red kidney bean lectin, phytohaemagglutinin (PHA) - a potent gut mitogen in adult rats - could accelerate the growth and maturation of the digestive system in suckling rats and piglets. Suckling rats and piglets were dosed with PHA either via enteral or parenteral administration for up to three consecutive days prior to natural weaning. The binding of PHA to the GI tract and extra-intestinal organs, GI organ growth, intestinal morphology and proliferation, disaccharidase activity pattern, and macromolecular absorption capacity were studied, as well as the pancreatic enzyme contents. Changes in these parameters were considered to be markers for maturation or development towards an adult-like GI function. Furthermore, the plasma levels of corticosterone and insulin (rat), and cholecystokinin (pig), were investigated. It was concluded that preweaning enteral exposure to PHA in suckling rats accelerated growth and induced precocious functional maturation of the GI tract and the pancreas. Similar results were also achieved when a crude PHA preparation was fed to suckling piglets. PHA treatment induced irreversible changes of the gut resembling those occurring at natural weaning, such as a reduced macromolecular absorption (intestinal closure), altered disaccharidase expression towards an adult-like activity pattern, and enhanced pancreas function. The ability of PHA to induce GI functional maturation in rats was age-dependent. Also, a direct binding and interaction of PHA with the GI epithelium was found to be a prerequisite to induce functional maturation, since parenteral administration had little effect. Shortly after administration, the binding of PHA to the intestinal epithelium temporarily caused mucosal disarrangement and functional impediment of the GI tract, probably resulting in the release of hormones and inflammatory cytokines. During a later phase, this led to a stimulatory response of the GI tract, as seen by an increase in crypt cell proliferation, gut growth, and the emergence of more adult-like enterocytes. Taking into consideration the temporal differences between rats and piglets with respect to natural maturational events, it was suggested that PHA exerted gut maturing effects in piglets and probably also in other mammals. Thus, these findings might lead to a better understanding of the role of the diet in GI functional maturation.