Analysis of Disialyllacto-N-Tetraose (DSLNT) Content in Milk From Mothers of Preterm Infants

Hassinger, Denise C.; Clausen, Dana M.; Nitka, Sarah A.; Herdt, Aimee; Griffin, Ian J.

doi:10.1177/0890334420904041

Cited by 12 publications

(18 citation statements)

References 14 publications

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“…The HMO results from the current study build upon previous findings in humans, showing reduced DSLNT in MOM received by infants developing NEC, independent of maternal secretor status (17)(18)(19). This is also supported by rodent studies where total and individual HMOs including 2'FL and DSLNT have shown a protective effect against NEC development (16,36,37).…”

Section: Discussionsupporting

confidence: 86%

“…A single MOM sample was analysed for each infant, as close to the onset of disease as possible, with control samples matched by day of life (DOL) (online supplementary figure 1). The median DOL of MOM from NEC cases was 18 (IQR 13-34) and from controls was also [18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The DOL of the milk sample is the DOL received by the infant, and is not necessarily the same day as the mother expressed the milk due to standard practice that often involves milk storage.…”

Section: Cohortmentioning

confidence: 99%

“…An association of lower DSLNT concentration in MOM and subsequent higher risk of NEC onset in the infant has since been observed in preterm human studies (17)(18)(19). To date, these studies have included very small numbers of infants with NEC (between 4 and 8), with a broad range of NEC phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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

Masi

Embleton

Lamb

et al. 2020

Gut

135

108

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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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Section: Discussionsupporting

confidence: 86%

Section: Cohortmentioning

confidence: 99%

See 1 more Smart Citation

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

Masi

Embleton

Lamb

et al. 2020

Gut

135

108

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“…Accordingly, to the above-listed inclusion criteria, the following data were excluded from the data analysis: Preterm milk data from eight articles [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Data from one article reporting concentration from Celiac positive mothers [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

The Mean of Milk: A Review of Human Milk Oligosaccharide Concentrations throughout Lactation

Soyyılmaz¹,

Mikš

Röhrig³

et al. 2021

Nutrients

127

102

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Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

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“…Following a similar model of investigation, early studies implicated DSLNT as an additional protective HMO in rodent models of NEC [183]. More recent epidemiological work has associated low levels of DSLNT in breastmilk with higher risk of NEC [184,185]. Thus, in the near future, supplementation of breastmilk or formula with HMOs may be a viable strategy for reducing the incidence of NEC among premature and low-birth-weight infants [186].…”

Section: Mitigating Inflammation Associated With Preterm Birthmentioning

confidence: 99%

Multifunctional Benefits of Prevalent HMOs: Implications for Infant Health

2021

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Breastfeeding is the best source of nutrition during infancy and is associated with a broad range of health benefits. However, there remains a significant and persistent need for innovations in infant formula that will allow infants to access a wider spectrum of benefits available to breastfed infants. The addition of human milk oligosaccharides (HMOs) to infant formulas represents the most significant innovation in infant nutrition in recent years. Although not a direct source of calories in milk, HMOs serve as potent prebiotics, versatile anti-infective agents, and key support for neurocognitive development. Continuing improvements in food science will facilitate production of a wide range of HMO structures in the years to come. In this review, we evaluate the relationship between HMO structure and functional benefits. We propose that infant formula fortification strategies should aim to recapitulate a broad range of benefits to support digestive health, immunity, and cognitive development associated with HMOs in breastmilk. We conclude that acetylated, fucosylated, and sialylated HMOs likely confer important health benefits through multiple complementary mechanisms of action.

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Analysis of Disialyllacto-N-Tetraose (DSLNT) Content in Milk From Mothers of Preterm Infants

Cited by 12 publications

References 14 publications

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

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

The Mean of Milk: A Review of Human Milk Oligosaccharide Concentrations throughout Lactation

Multifunctional Benefits of Prevalent HMOs: Implications for Infant Health

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