Abstract
BackgroundThe preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. From a cohort of 318 infants, <32 weeks gestation, we selected 7 infants who developed NEC (defined rigorously) and 28 matched controls. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease.ResultsA core community of Klebsiella, Escherichia, Staphyloccocus, and Enterococcus was present in all samples. Gut microbiota profiles grouped into six distinct clusters, termed preterm gut community types (PGCTs). Each PGCT reflected dominance by the core operational taxonomic units (OTUs), except of PGCT 6, which had high diversity and was dominant in bifidobacteria. While PGCTs 1–5 were present in infants prior to NEC diagnosis, PGCT 6 was comprised exclusively of healthy samples. NEC infants had significantly more PGCT transitions prior to diagnosis. Metabolomic profiling identified significant pathways associated with NEC onset, with metabolites involved in linoleate metabolism significantly associated with NEC diagnosis. Notably, metabolites associated with NEC were the lowest in PGCT 6.ConclusionsThis is the first study to integrate sequence and metabolomic stool analysis in preterm neonates, demonstrating that NEC does not have a uniform microbial signature. However, a diverse gut microbiome with a high abundance of bifidobacteria may protect preterm infants from disease. These results may inform biomarker development and improve understanding of gut-mediated mechanisms of NEC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0216-8) contains supplementary material, which is available to authorized users.
Highlights
The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants
The developing gut microbiome in patients diagnosed with NEC was highly dynamic and individual, with no clear causative organism identified in the patients diagnosed with NEC (Additional file 1: Figure S1 and Additional file 2: Table S1)
In accordance with existing data, we found that control infants have increasing diversity whereas patients diagnosed with NEC have significantly reduced diversity while on the neonatal intensive care unit (NICU) [10, 19, 20], the microbiome of NEC infants converge to that of controls within 1 year following NICU discharge [24]
Summary
The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease. Survival after preterm birth is increasing, but this is associated with increased numbers of infants developing necrotising enterocolitis (NEC) and late onset sepsis (LOS), with ~10% and ~20% of very low birth weight (VLBW) infants being affected, respectively [1]. Moving beyond 16S rRNA bacterial profiling, a metagenomic (shotgun sequencing) study of NEC samples during an apparent outbreak found no distinct microbial strain in NEC infants at the time of diagnosis [12]. Studies have reported an absence of “pathogenic” bacteria in tissue resections from NEC infants [13] and no difference in the total bacterial load [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
