Patterned progression of gut microbiota associated with necrotizing enterocolitis and late onset sepsis in preterm infants: a prospective study in a Chinese neonatal intensive care unit

Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are two common premature birth complications with high morbidity and mortality. Recent studies in Europe and America have linked gut microbiota dysbiosis to their etiology. However, similar studies in Asian populations remain scant. In this pilot study, we profiled gut microbiota of 24 Chinese preterm infants from birth till death or discharge from NICU. Four of them developed NEC and three developed LOS. Unexpectedly, we detected highly-diversified microbiota with similar compositions in all patients shortly after birth. However, as patients aged, the microbial diversities in case groups differed significantly from that of the control group. These differences emerged after the third day of life and persisted throughout the course of both NEC and LOS. Using a Zero-Inflated Beta Regression Model with Random Effects (ZIBR), we detected higher Bacillus (p = 0.032) and Solibacillus (p = 0.047) before the onset of NEC and LOS. During NEC progression, Enterococcus, Streptococcus and Peptoclostridium were the dominant genera while during LOS progression; Klebsiella was the only dominant genus that was also detected by the diagnostic hemoculture. These results warrant further studies to identify causative microbial patterns and underlying mechanisms.