Rapamycin, a specific inhibitor of the target of rapamycin complex 1, disrupts intestinal barrier integrity in broiler chicks

Abstract

To uncover the molecular mechanisms underlying the intestinal barrier integrity, this study determined whether the rapamycin (RAPA)-sensitive target of rapamycin complex 1 (TORC1) pathway was involved in this process. Three groups of 4-day-old male chicks were randomly subjected to one of the following treatments for 6 days: high-dose RAPA [a specific inhibitor of TORC1; an intraperitoneal injection of 1.0 mg/kg body weight (BW), once daily at 09:00 hours], low-dose RAPA (0.4 mg/kg BW) and RAPA vehicle (control). Results showed that the RAPA treatment increased mortality, while decreasing villus height (p < 0.01), claudin 1 expression, content of immunoglobulin A (IgA), extent of TORC1 phosphorylation (p < 0.05), ratio of villus height to crypt depth (p < 0.01), and population of IgA-positive B cells in intestinal mucosa, particularly for the jejunum. Some aspects of these responses were dose dependent and appeared to result from weight loss. Together, RAPA exerts the expected inhibition of small intestinal development and IgA production in birds, suggesting the important role of TORC1 in gut barrier integrity.