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Lookup NU author(s): Andrea Masi,
Professor Nicholas EmbletonORCiD,
Dr Chris LambORCiD,
Dr Claire Granger,
Dr Janet Berrington,
Dr Christopher Stewart
This is the authors' accepted manuscript of an article that has been published in its final definitive form by BMJ Publishing Group, 2020.
For re-use rights please refer to the publisher's terms and conditions.
Objective: Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mothers own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC. Design: We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 NEC) we also performed longitudinal metagenomic sequencing of infant stool (n=644). Results: Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by NEC infants compared to controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp. and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or NEC. Conclusion: These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification, and novel avenues for supplements that may prevent life-threatening disease.
Author(s): Masi AC, Embleton ND, Lamb CA, Young G, Granger CL, Najera JA, Smith DP, Hoffman KL, Petrosino JF, Bode L, Berrington JE, Stewart CJ
Publication type: Article
Publication status: Published
Pages: epub ahead of print
Online publication date: 16/12/2020
Acceptance date: 30/11/2020
Date deposited: 02/12/2020
ISSN (print): 0017-5749
ISSN (electronic): 1468-3288
Publisher: BMJ Publishing Group
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