We suggest that where NEC is associated with an Enterobacteriaceae-dominated microbiota the pathological basis for the epithelial necrosis is overstimulation of TLR4 by over-abundant LPS, while where the association is with the bloom of a pathogen like C. perfringens, it is the (strikingly) low CpG frequency in the resulting microbiota that leads to a failure of counter-regulation of TLR4 through TLR9. Here, TLR9 is linked to necrotizing enterocolitis.