Toggle Main Menu Toggle Search

Open Access padlockePrints

Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis

Lookup NU author(s): Andrea Masi, Professor Nicholas EmbletonORCiD, Dr Chris LambORCiD, Grace Young, Dr Claire Granger, Dr Janet Berrington, Dr Christopher Stewart

Downloads


Licence

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.


Abstract

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.


Publication metadata

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

Journal: Gut

Year: 2020

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

URL: https://doi.org/10.1136/gutjnl-2020-322771

DOI: 10.1136/gutjnl-2020-322771


Altmetrics

Altmetrics provided by Altmetric


Share