Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants

Abstract

Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; <1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3′-sialyllactose and 6′-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review

“…Mechanistically, HMO-2′FL maintained mesenteric perfusion of the gut with preserved expression of endothelial nitric oxide synthase in the intestine [ 34 ]. A recent analysis of HMOs in breast milk from 91 mothers of extremely low birth weight infants (<1000 g) at day 14, 28, and at postmenstrual week 36 showed that the development of NEC was associated with lower levels of the fucosylated HMO lacto-N-difucohexaose (LNDH I) [ 35 ]. Additionally, low levels of HMOs sialyl-lacto-N-tetraose a (LSTa) and lacto-N-neotetraose (LNnT) at the 28-day time point were associated with the development of NEC [ 35 ].…”

“…A recent analysis of HMOs in breast milk from 91 mothers of extremely low birth weight infants (<1000 g) at day 14, 28, and at postmenstrual week 36 showed that the development of NEC was associated with lower levels of the fucosylated HMO lacto-N-difucohexaose (LNDH I) [ 35 ]. Additionally, low levels of HMOs sialyl-lacto-N-tetraose a (LSTa) and lacto-N-neotetraose (LNnT) at the 28-day time point were associated with the development of NEC [ 35 ]. Further analysis showed that high levels of 6′SL and low levels of 3′SL at the 28-day time point was associated with the development of sepsis [ 35 ].…”

“…Additionally, low levels of HMOs sialyl-lacto-N-tetraose a (LSTa) and lacto-N-neotetraose (LNnT) at the 28-day time point were associated with the development of NEC [ 35 ]. Further analysis showed that high levels of 6′SL and low levels of 3′SL at the 28-day time point was associated with the development of sepsis [ 35 ]. In contrast, a model of NEC in preterm piglets receiving feeds with a complex blend of HMOs showed no significant difference in intestinal microbial diversity or protection against NEC [ 36 ].…”

Effects of Lactobacillus plantarum 15-1 and fructooligosaccharide on the response of broilers to pathogenic Escherichia coli O78 challenge

“…E. coli is associated with the deterioration of animal health, including weight loss, diarrhea, mortality, and necrotizing enteritis [23]. Gaëlle Porcheron’s [24] research shows that FOS may be capable of regulating an extra-intestinal pathogenic Escherichia coli strain, and this property is associated with a gene cluster called the fos locus, plays a major intestinal colonization, which brings good results that the probiotic bacteria of the microbiota can metabolize in the intestine and decrease the population of pathogenic bacteria.…”

Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Activating Intestinal Cell Differentiation

“…[6] In addition, the diversity of the pooled HMOs composition (Shannon's H: 2.27) also fits within previous human studies. [18] To determine host transcriptomic responses following exposure to pooled HMOs, Caco-2Bbe1 (Caco-2) cells were treated with either phosphate buffered saline (PBS) or 20 mg mL −1 HMOs for 24 h prior to global mRNA profiling using RNA sequencing ( Figure 1A). HMOs-treated cells exhibited a distinct transcriptome compared to PBS-treated controls.…”