Human milk oligosaccharides 3′-sialyllactose and 6′-sialyllactose protect intestine against necrotizing enterocolitis damage induced by hypoxia

[Display omitted] •3′-SL and 6′-SL attenuated intestinal hypoxic injury in vitro and vivo.•3′-SL and 6′-SL mixture protected intestine against the damage induced by NEC.•3′-SL and 6′-SL mixture inhibited the activation of the TLR4/NF-κB pathway. In premature infants, necrotizing enterocolitis (NEC) is one of the most prevalent diseases among premature infants and has a high mortality rate. Previous studies have shown that human milk oligosaccharides (HMOs) could effectively decrease the incidence of NEC. However, it is not known whether the efficacy of oligosaccharides is related to their structure. We found that among the HMOs, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) significantly restored proliferation, reduced apoptosis, and relieved inflammation of the intestinal cells of neonatal mice under hypoxia. In addition, our findings indicated that 3′-SL and 6′-SL provide protection against NEC-induced intestinal damage by inhibiting the activation of the TLR4/NF-κB pathway. In sum, 3′-SL and 6′-SL, which are formed when Sia monosaccharide is linked to lactose, are HMO components that can effectively alleviate hypoxia-induced damage in NEC and should be considered as a potential nutritional supplement that can be added to infant formula.