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.

Jiayi Liu,Jianhua Zhao,Li Hong,Zhilong Yan,Jianhua Sun,Zhoulonglong Xie,Yi Feng,Li Zhang,Yuqing Li,Liya Pan,Mingkun Li

doi:10.7717/peerj.7310

Jiayi Liu, Jianhua Zhao + Show 9 more

Open Access

https://doi.org/10.7717/peerj.7310

Copy DOI

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.

Highlights

The gut microbiota is a crucial contributor to human health
From July 2013 to December 2014, a total of 130 preterm infants admitted to the neonatal intensive care unit (NICU) of Shanghai Children’s Medical Center met the criteria of our study and a total of 1698 samples were collected. 192 fecal samples from 24 well-sampled preterm infants were sequenced
We used generation-sequencing to profile the microbiota of 24 Chinese preterm infants from birth to discharge

Summary

Introduction

The gut microbiota is a crucial contributor to human health. Imbalance of the microbial community, termed dysbiosis, is associated with various diseases, such as obesity and diabetes (Bouter et al, 2017; Rosenbaum, Knight & Leibel, 2015; Winer et al, 2016; Cani, 2019; Zmora, Suez & Elinav, 2019), immunity-related diseases (Vogelzang et al, 2018; Pronovost & Hsiao, 2019; Vatanen et al, 2016), neurodevelopmental disorders (Sampson & Mazmanian, 2015; Pronovost & Hsiao, 2019), cardiovascular diseases (Tang, Kitai & Hazen, 2017; Jie et al, 2017; Jonsson & Bckhed, 2017) and cancers (Gagliani et al, 2014; Irrazábal et al, 2014; Sears & Garrett, 2014).The microbiota in newborn infants undergoes dynamic changes in composition, abundance and diversity before reaching homeostasis at around three years of age (Yatsunenko et al, 2012; Bäckhed et al, 2015; Stewart et al, 2018). The gut microbiota is a crucial contributor to human health. Temporal colonization pattern of the intestinal microbiota during early stages of life may have an important contribution to the long term health of an individual. Life microbiota disruption had been associated with the development of metabolic and immunological diseases such as Type I diabetes (Giongo et al, 2011; Vatanen et al, 2018), asthma (Stokholm et al, 2018) and allergies (Madan et al, 2012a; Savage et al, 2018). Resultant abnormal microbiota colonization in the gut may contribute complications such as necrotizing enterocolitis (NEC) and late onset sepsis (LOS) (Sharon et al, 2015; Cernada et al, 2016)

Methods

Results

Discussion

Conclusion