Abstract

Background: Necrotizing enterocolitis (NEC) is a devastating condition in preterm infants due to multiple factors, including gut microbiota dysbiosis. NEC development is poorly understood, due to the focus on severe NEC (NEC-2/3). Methods: We studied the gut microbiota, microbiome and metabolome of children with suspected NEC (NEC-1). Results: NEC-1 gut microbiota had a higher abundance of the Streptococcus (second 10-days of life) and Staphylococcus (third 10-days of life) species. NEC-1 children showed a microbiome evolution in the third 10-days of life being the most divergent, and were associated with a different metabolomic signature than in healthy children. The NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first 10-days of life, and was more sensitive to childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life. Conclusions: NEC-1 gut microbiota and microbiome modifications appear more distinguishable by the third 10-days of life, compared to healthy children. These data identify a precise window of time (i.e., the third 10-days of life) and provide microbial targets to fight/blunt NEC-1 progression.

Highlights

  • Necrotizing enterocolitis (NEC), defined by the Bell classification [1,2,3], is the most severe intestinal disease in preterm infants, with a mortality score of 25% and long-term neurological morbidity [4]

  • To understand the microbial and metabolomic evolution during the early onset of necrotizing enterocolitis (NEC), we studied clinical profile suspected NEC (NEC-1) preterm infants

  • NEC-1 microbiome showed increased activity for pathway related to transcription, glycosaminoglycan degradation and lysosome, compared to healthy children (Supplementary Figure S2D)

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Summary

Introduction

Necrotizing enterocolitis (NEC), defined by the Bell classification [1,2,3], is the most severe intestinal disease in preterm infants, with a mortality score of 25% and long-term neurological morbidity [4]. Gut microbiota was identified and recognized as a specific organ with functions widely beyond digestion [5] Both its taxonomic (relative abundance) and functional (microbial pathway) alterations, named dysbiosis, were described in several pathologies, in particular, metabolic diseases such as type 2 diabetes and obesity [6,7,8], and intestinal inflammatory diseases [9,10]. Conclusions: NEC-1 gut microbiota and microbiome modifications appear more distinguishable by the third 10-days of life, compared to healthy children. These data identify a precise window of time (i.e., the third 10-days of life) and provide microbial targets to fight/blunt NEC-1 progression

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