Gut microbiota composition in preterm infants with and without necrotizing enterocolitis: A systematic review and narrative synthesis

Aim Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disorder in preterm infants with a high mortality rate. The etiology of NEC appears to be multifaceted; however, gut microbiota dysbiosis likely plays a significant role. This systematic review aimed to describe how the gut microbiota of preterm infants with NEC differs from infants without NEC (PROSPERO: CRD42022344126). Methods Databases were searched from inception to 22 June 2022 to identify eligible studies that examined the gut microbiota composition of preterm infants with and without NEC using sequencing methods. Results were described narratively. Results Twenty-eight eligible studies were included. Overall, findings were heterogeneous and no single gut microbiota signature was associated with NEC in all studies. Three studies reported no difference in the gut microbiota composition between NEC and healthy infants, while twenty-five studies reported a difference using one or more analytical method (i.e. alpha diversity, beta diversity or differential abundance analysis). Of note, NEC (or development of NEC) was positively associated with increased detection and/or abundance of Enterobacteriaceae (n=11 studies), Clostridium (n=8), and Proteobacteria (n=2). Conclusion The taxa most frequently associated with NEC (Enterobacteriaceae, Clostridium, and Proteobacteria) may play an important role in the pathogenesis of NEC and should be further explored.