Sialylated human milk oligosaccharides prevent intestinal inflammation by inhibiting toll like receptor 4/NLRP3 inflammasome pathway in necrotizing enterocolitis rats

Abstract Background Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes experimental NEC models. The objectives of this study were to investigate the involvement NLRP3 inflammasome pathology explore effects SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway NEC. Methods intestinal-tissue segments collected from infants, caspase-1 positive cell examined by immunohistochemistry. Newborn rats hand-fed with formula containing or non-containing (1500 mg/L) exposed hypoxia/cold stress induce scores evaluated; ileum protein expression membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit phospho-NF-κB p65, as well analyzed; concentrations interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α) also measured. Human colon epithelial Caco-2 cells pre-treated without stimulated activator, lipopolysaccharide. Cell viabilities, mitochondrial potential supernatant matrix metalloprotease 2 (MMP-2) activities analyzed. Results Increased frequencies found lamina propria damaged intestinal area neonates. supplementation reduced incidence damage challenged stress. Accumulation interleukin-6 TNF-α group attenuated + group. Protein mTLR4, elevated, cytoplasmic IκB-α reduced, nuclear increased rats. ameliorated elevation caspase-1, restored fraction pre-treatment improved viability, mitigated loss modulated MMP-2 presence lipopolysaccharide in-vitro. Conclusions This provided clinical evidence pathology, demonstrated protective actions might be owing suppression TLR4/NF-κB/NLRP3-mediated inflammation