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

Abstract

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. We report that like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. 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. The expression of lysozyme, secretory phospholipase A2, pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF (NEC) group, compared to the DF and FF+BIF groups where disease was attenuated. 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.

Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model

“…Armogida et al (7) reported that the presence of mediators of the innate immune system in human milk, including hBD3 provided protection for the developing digestive tract of newborns. In addition, defensins induction seemed to be a common and important mechanism of probiotics treatment (8,9). Collectively, these studies suggested an important role of defensins in neonatal mucosal defense and intestinal barrier function.…”

Pathogenesis of NEC: Role of the innate and adaptive immune response

“…Premature infants have been shown to have fewer Paneth cells with decreased function 191,199,201,202 . Multiple animal studies implicate the importance of Paneth cells in NEC pathogenesis 203,204 . Preterm infants with NEC have been shown to have normal 4 to reduced 122,205,206 numbers of Paneth cells or poorly functioning Paneth cells 202,206 , but infants recovering from NEC have been shown to demonstrate Paneth cell hyperplasia 207 .…”

Impact of probiotics on necrotizing enterocolitis

“…44 In the rat model of NEC, B. bifidum decreases the incidence and severity of NEC, attenuates induction of IL6, attenuates induction of trefoil factor 3 and several antimicrobial peptides, improves barrier function, activates TLR2, and decreases apoptosis. 45-47 …”