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

Abstract

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.

Clinical characteristics influence cultivable-bacteria composition in the meconium of Indonesian neonates

“…In contrast to Mai et al, Bacillus and Solibacillus (Firmicutes) were over-represented three days before the onset of NEC and LOS, as reported by [ 38 ]. This finding supported our data, which found Firmicutes as the most dominant phylum in both groups.…”

“…Gut microbiota is also closely linked with neonatal sepsis and NEC. Microbiota profile of neonates diagnosed with NEC and late-onset sepsis (LOS) were reported to have lower diversity even when compared to preterm infants [ 37 , 38 ]. Mai et al [ 39 ] reported four phyla (i.e., Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria), which dominated the microbiota of the fecal sample.…”

“…This finding supported our data, which found Firmicutes as the most dominant phylum in both groups. LOS patients were found to have a higher abundance of Klebsiella in their gut microbiota during LOS progression [ 38 ]. The most dominant and infectious bacteria in the hospital environment could cause LOS [ 38 ].…”

Ulinastatin Reduces the Severity of Intestinal Damage in the Neonatal Rat Model of Necrotizing Enterocolitis

“…Premature infants with NEC usually have low birth weight and young gestational age [5]. Though the much improvement of neonatal care has greatly improved the survival rate of premature infants, the risk of NEC is also increasing [6]. Thus, novel treatment options are expected to assist treat and prevent the development and progression of the disease [7].…”

Neonatal intestinal dysbiosis

“…Microbiota composition "immaturity" is a term coined for a delay of the patterned progression of the microbiota. It is characteristic of severe acute malnutrition in children [37] and may be another useful definition of dysbiosis in the infant [38][39][40].…”