Necrotizing enterocolitis, gut microbes, and sepsis

ABSTRACT

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants and the leading cause of death and disability from gastrointestinal disease in this vulnerable population. Although the pathophysiology of NEC remains incompletely understood, current thinking indicates that the disease develops in response to dietary and bacterial factors in the setting of a vulnerable host. As NEC progresses, intestinal perforation can result in serious infection with the development of overwhelming sepsis. In seeking to understand the mechanisms by which bacterial signaling on the intestinal epithelium can lead to NEC, we have shown that the gram-negative bacterial receptor toll-like receptor 4 is a critical regulator of NEC development, a finding that has been confirmed by many other groups. This review article provides recent findings on the interaction of microbial signaling, the immature immune system, intestinal ischemia, and systemic inflammation in the pathogenesis of NEC and the development of sepsis. We will also review promising therapeutic approaches that show efficacy in pre-clinical studies.

KEYWORDS:

• premature
• necrotizing enterocolitis (NEC)
• microbes
• sepsis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data of this study are openly available at http://dx.doi.org/10.1080/19490976.2023.2221470.

Additional information

Funding

DJH is supported by R35GM141956 from the National Institutes of Health; CML and DS are supported by T32DK007713.