Necrotizing enterocolitis is a leading cause of death in preterm infants and is characterized by severe inflammation. The incidence of necrotizing enterocolitis is reduced in preterm infants fed human breast milk; however, the factors underlying the beneficial effects of human breast milk are not fully understood. In this episode, Mansour Mohamadzadeh and colleagues compared the microbiome of preterm infants fed either breast milk or formula and identified a propionobacterial strain (P. FU1) that was present in the gut microbiota of breastmilk fed- but not formula fed-infants. Moreover, introduction of this bacterial strain into murine models was protective against necrotizing enterocolitis-like inflammation and injury as well pathogenic intestinal pathogens. The results of this study provide important insight into the beneficial effects of human breast milk on intestinal flora.
Consumption of human breast milk (HBM) attenuates the incidence of necrotizing enterocolitis (NEC), which remains a leading and intractable cause of mortality in preterm infants. Here, we report that this diminution correlates with alterations in the gut microbiota, particularly enrichment of Propionibacterium species. Transfaunation of microbiota from HBM-fed preterm infants or a newly identified and cultured Propionibacterium strain, P. UF1, to germfree mice conferred protection against pathogen infection and correlated with profound increases in intestinal Th17 cells. The induction of Th17 cells was dependent on bacterial dihydrolipoamide acetyltransferase (DlaT), a major protein expressed on the P. UF1 surface layer (S-layer). Binding of P. UF1 to its cognate receptor, SIGNR1, on dendritic cells resulted in the regulation of intestinal phagocytes. Importantly, transfer of P. UF1 profoundly mitigated induced NEC-like injury in neonatal mice. Together, these results mechanistically elucidate the protective effects of HBM and P. UF1–induced immunoregulation, which safeguard against proinflammatory diseases, including NEC.
Natacha Colliou, Yong Ge, Bikash Sahay, Minghao Gong, Mojgan Zadeh, Jennifer L. Owen, Josef Neu, William G. Farmerie, Francis Alonzo III, Ken Liu, Dean P. Jones, Shuzhao Li, Mansour Mohamadzadeh