Altered gut microbiome and fecal immune phenotype in early preterm infants with leaky gut

Intestinal barrier immaturity, or "leaky gut," is the proximate cause of susceptibility to necrotizing enterocolitis (NEC) in preterm neonates. Exacerbated intestinal immune responses, microbial community dysbiosis, and heightened barrier injury are considered primary triggers of aberrant intestinal maturation in early life. Disordinate host immunity was considered to contribute to this process, but the precise elements remain largely uncharacterized, leaving a significant knowledge gap in the biological underpinnings of gut maturation. In this study, we investigated the fecal cytokine profile and gut microbiota of a cohort of 40 early preterm infants <33-weeks-gestation to identify markers of intestinal barrier maturation. Three distinct microbiota types were demonstrated to be associated differentially with intestinal permeability (IP), maternal breastmilk feeding as well as immunological profiles. The Staphylococcus epidermidis- and Enterobacteriaceae-predominant microbiota types associated with an elevated IP and less breastmilk intake demonstrated a highly varied and less defined cytokine profile. On the other hand, a significantly lowered IP is associated with increased levels of IL-1 alpha and the microbiota type with a wide array of anaerobes in an expanded fermentative capacity. Our study demonstrated the critical role of both immunological and microbiological factors in the early development of intestinal barrier, that collectively form the intestinal microenvironment determining gut homeostasis and affecting postnatal intestinal maturation in early preterm newborns.