TLR4 and necrotizing enterocolitis: This model led to the demonstration that breast milk protects against NEC (Barlow et al., 1974; Caplan et al., 1994), and also identified a role for nitric oxide in the pathogenesis of NEC (Nadler et al., 2000), the importance of bacterial colonization and TLR4 activation (Jilling et al., 2006), and the protective effects of beneficial commensal bacteria (Caplan et al., 1999), epidermal growth factor (Dvorak et al., 2002) and HMOs (Jantscher-Krenn et al., 2012).