Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum

ObjectiveNecrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother’s 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.DesignWe 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 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644).ResultsConcentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with 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 having NEC.ConclusionThese 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.

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Correction to: Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota

Microbial Cell Factories ◽

10.1186/s12934-021-01612-4 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Shunhao Zhang ◽

Tianle Li ◽

Jing Xie ◽

Demao Zhang ◽

Caixia Pi ◽

...

Keyword(s):

Gut Microbiota ◽

Human Milk ◽

Gold Standard ◽

Milk Oligosaccharide ◽

Human Milk Oligosaccharide

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Human Milk Oligosaccharide Profile Variation Throughout Postpartum in Healthy Women in a Brazilian Cohort

Nutrients ◽

10.3390/nu12030790 ◽

2020 ◽

Vol 12 (3) ◽

pp. 790 ◽

Cited By ~ 3

Author(s):

Ana Lorena Ferreira ◽

Ronaldo Alves ◽

Amanda Figueiredo ◽

Nadya Alves-Santos ◽

Nathalia Freitas-Costa ◽

...

Keyword(s):

Human Milk ◽

Rank Correlation ◽

Postpartum Visit ◽

Maternal Characteristics ◽

Milk Oligosaccharide ◽

Healthy Women ◽

Human Milk Oligosaccharide ◽

Post Hoc ◽

Brazilian Cohort ◽

Non Negative Matrix Factorization

Human milk oligosaccharide (HMO) composition varies throughout lactation and can be influenced by maternal characteristics. This study describes HMO variation up to three months postpartum and explores the influences of maternal sociodemographic and anthropometric characteristics in a Brazilian prospective cohort. We followed 101 subjects from 28–35 gestational weeks (baseline) and throughout lactation at 2–8 (visit 1), 28–50 (visit 2) and 88–119 days postpartum (visit 3). Milk samples were collected at visits 1, 2 and 3, and 19 HMOs were quantified usinghigh-performance liquid chromatography with fluorescence detection (HPLC-FL). Friedman post-hoc test, Spearman rank correlation for maternal characteristics and HMOs and non-negative matrix factorization (NMF) were used to define the HMO profile. Most women were secretors (89.1%) and presented high proportion of 2′-fucosyllactose (2′FL) at all three sample times, while lacto-N-tetraose (LNT, 2–8 days) and lacto-N-fucopentaose II (LNFPII, 28–50 and 88–119 days) were the most abundant HMOs in non-secretor women. Over the course of lactation, total HMO weight concentrations (g/L) decreased, but total HMO molar concentrations (mmol/L) increased, highlighting differential changes in HMO composition over time. In addition, maternal pre-pregnancy body mass index (BMI) and parity influence the HMO composition in healthy women in this Brazilian cohort.

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