In conclusion, this study (1) provided evidence of increased frequencies of NLRP3 and caspase-1 positive cells in the lamina propria of damaged intestinal areas in NEC infants; (2) showed SHMOs inhibited TLR4/NF-κB/NLRP3 signaling pathway, suppressed inflammatory cytokines (IL-1β, TNF-α and IL-6) production and reduced NEC incidence and pathological damages in inflamed ileum of NEC rats in-vivo; (3) suggested SHMOs promoted epithelial cell proliferation, restored mitochondrial membrane potential and regulated MMP-2 activities in LPS-stimulated Caco-2 cells in-vitro. Here, IL6 is linked to necrotizing enterocolitis.