Bifidobacterium bifidum in a rat model of necrotizing enterocolitis: antimicrobial peptide and protein responses.

INTRODUCTION: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. METHODS: To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF + BIF). All groups were exposed to asphyxia and cold stress. RESULTS: Like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. The expression of lysozyme, secretory phospholipase A(2) (sPLA(2)), pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF group with a high incidence of NEC, as compared with the DF and FF + BIF groups where the disease was attenuated. DISCUSSION: We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut.

Epidermal growth factor and necrotizing enterocolitis.

PURPOSE OF REVIEW: This review will summarize the clinical and experimental studies evaluating the role of epidermal growth factor (EGF) in prophylaxis and treatment of necrotizing enterocolitis (NEC). RECENT FINDINGS: Clinical studies have suggested the importance of EGF in protection of the intestine against NEC, as well as its safety for infants suffering from NEC. The recent experimental studies identified the molecular mechanisms EGF uses for intestinal protection, which involves regulation of intestinal epithelial homeostasis and barrier function. Further studies are necessary to identify the optimal dose, timing, and route of administration of EGF to NEC patients. No clinical studies are currently underway. SUMMARY: NEC is a devastating problem for preterm neonates, but the exact disease pathogenesis remains unclear. Growing clinical evidence supports the use of EGF as a predictive marker of NEC and its use for prevention and treatment of NEC. In addition, experimental data indicate potential mechanisms of EGF prevention against NEC. These include reduction of inflammation, improvement of barrier function, and regulation of epithelial apoptosis and autophagy.

Clostridium perfringens alpha toxin is produced in the intestines of broiler chicks inoculated with an alpha toxin mutant.

Poultry necrotic enteritis (NE) is caused by specific strains of Clostridium perfringens, most of which are type A. The role of alpha toxin (CPA) in NE has been called into question by the finding that an engineered cpa mutant retains full virulence in vivo[9]. This is in contrast to the finding that immunization with CPA toxoids protects against NE. We confirmed the earlier findings, in that 14-day-old Cornish × Rock broiler chicks challenged with a cpa mutant developed lesions compatible with NE in >90% of birds inoculated with the mutant. However, CPA was detected in amounts ranging from 10 to >100 ng per g of gut contents and mucosa in birds inoculated with the cpa mutant, the wildtype strain from which the mutant was constructed, and our positive control strain. There was a direct relationship between lesion severity and amount of CPA detected (R = 0.89-0.99). These findings suggest that the role of CPA in pathogenesis of NE requires further investigation.