Longitudinal gut virome analysis identifies specific viral signatures that precede necrotizing enterocolitis onset in preterm infants

Abstract

Necrotizing enterocolitis (NEC) is a serious consequence of preterm birth and is often associated with gut bacterial microbiome alterations. However, little is known about the development of the gut virome in preterm infants, or its role in NEC. Here, using metagenomic sequencing, we characterized the DNA gut virome of 9 preterm infants who developed NEC and 14 gestational age-matched preterm infants who did not. Infants were sampled longitudinally before NEC onset over the first 11 weeks of life. We observed substantial interindividual variation in the gut virome between unrelated preterm infants, while intraindividual variation over time was significantly less. We identified viral and bacterial signatures in the gut that preceded NEC onset. Specifically, we observed a convergence towards reduced viral beta diversity over the 10 d before NEC onset, which was driven by specific viral signatures and accompanied by specific viral-bacterial interactions. Our results indicate that bacterial and viral perturbations precede the sudden onset of NEC. These findings suggest that early life virome signatures in preterm infants may be implicated in NEC.

Necrotizing enterocolitis: Bench to bedside approaches and advancing our understanding of disease pathogenesis

“…In another recent study, stool samples obtained from 9 infants with NEC infants and 14 controls matched for weight and gestational age, showed reduced viral beta diversity over the 10 days before NEC onset. This study also identified that viral NEC-associated contigs belonging to Myoviridae , Podoviridae and Siphoviridae are associated with the time period 0–10 d post NEC onset ( 137 ).…”

Machine Learning Advances in Microbiology: A Review of Methods and Applications

“…For instance, VirSorter searches the database of expected proteins up front using probabilistic similarity and reference homology to identify viral signals, but the disadvantage is that it does not fully distinguish between virus and nonvirus Pfam annotations ( Roux et al, 2015 ). Kaelin et al (2022) employed VirSorter v.1.0.5 to identify circular contigs of candidate viruses. Another tool, Meta-genomic Analysis and Retrieval of Viral Elements (MARVEL), which aggregates annotation and sequence signature information of previously identified phages, was developed to identify and predict double-stranded DNA phage sequences in macrogenomic boxes.…”

The gut virome in health and disease: new insights and associations

“…Understanding the development and maturation of the infant virome may uncover alterations that predict disease. In a study of necrotizing enterocolitis (NEC), a condition consisting of inflammation in intestinal tissue in preterm infants, Kaelin et al [33 ] studied the virome in preterm infants and its association with NEC. This condition is thought to be associated with gut bacterial alterations [34,35].…”

“…This condition is thought to be associated with gut bacterial alterations [34,35]. Metagenomic sequencing of the gut virome of nine preterm infants who developed NEC and 14 gestational age-matched preterm infants were characterized [33 ▪ ]. Longitudinal sampling before NEC onset was conducted over the first eleven weeks of life.…”