Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study

Abstract

Background: Human milk oligosaccharides are complex, non-digestible carbohydrates that directly interact with intestinal epithelial cells to alter barrier function and host inflammation. Oligosaccharide composition varies widely between individual mothers, but it is unclear if this inter-individual variation has any impact on intestinal epithelial barrier function and gut inflammation. Methods: Human milk oligosaccharides were extracted from the mature human milk of four individual donors. Using an in vitro model of intestinal injury, the effects of the oligosaccharides on the intestinal epithelial barrier and select innate and adaptive immune functions were assessed. Results: Individual oligosaccharide compositions shared comparable effects on increasing transepithelial electrical resistance and reducing the macromolecular permeability of polarized (Caco-2Bbe1) monolayers but exerted distinct effects on the localization of the intercellular tight junction protein zona occludins-1 in response to injury induced by a human enteric bacterial pathogen Escherichia coli, serotype O157:H7. Immunoblots showed the differential effects of oligosaccharide compositions in reducing host chemokine interleukin 8 expression and inhibiting of p38 MAP kinase activation. Conclusions: These results provide evidence of both shared and distinct effects on the host intestinal epithelial function that are attributable to inter-individual differences in the composition of human milk oligosaccharides.

Variations in Oligosaccharides and N/O-Glycans in Human Milk through the Eight-Month Lactation Period

“…For instance, glycans provide sialic acid needed for the baby’s brain development . About 70–83% of all sialic acid present in human milk is bound with HMOs, 14–28% with glycoprotein glycans and 0.2–0.4% with glycolipids (primarily gangliosides). , In addition, oligosaccharides act as a metabolic substrate to shape the intestinal flora, − serve as antiadhesive antimicrobials, and modulate epithelial and immune cell responses, thereby contributing to immune protection. , And N -glycans simultaneously contribute to antibacterial, antiviral, and immune system regulation, , and O -glycans affect the formation and stability of the intestinal microbiota and act as effective decoy receptors for pathogenic gastrointestinal bacteria and viruses . The different glycans consumed in early life are suggested to be associated with differences in long-term health conditions and intelligence between breastfed and bottle-fed infants. − Hence, insights into the composition and variation of oligosaccharides and N / O -glycans in babies’ early life are urgently needed for the innovation and improvement of infant formula.…”

Human Milk Oligosaccharides Are Present in Amniotic Fluid and Show Specific Patterns Dependent on Gestational Age

“…Similar to human subjects, AF has also been shown to reduce gut inflammatory processes and NEC severity in mice [ 34 ] and preterm pigs [ 41 ]. Porcine or human AF decreased intestinal inflammatory cytokines and increased body weight [ 42 ], inviting speculation that HMOs account for these effects of AF, similar to direct HMO effects observed in vitro [ 22 , 23 , 43 ]. Thus, our findings may be valuable for developing future preventive approaches for infants at risk of VLBW.…”

“…Animal studies have suggested that sialylated HMOs, potentially by providing sialic acid as building block for brain gangliosides, promote neuronal and brain development and might have long-lasting effects on the development of cognitive functions [ 20 , 21 ]. Moreover, several studies have suggested HMO effects on intestinal barrier function, mucosal immune maturation and neonatal intestinal development [ 22 , 23 , 24 ].…”

Human Milk Oligosaccharides: A Critical Review on Structure, Preparation, Their Potential as a Food Bioactive Component, and Future Perspectives

“…HMOs can adjust the intestinal epithelial cells as a signal molecule reaction. Wu and co-workers used the intestinal injury model induced by EHEC O157:H7 to evaluate the effect of HMOs on the intestinal epithelial barrier and the selection of innate and adaptive immune functions . The research showed that HMOs could prevent changes in the integrity of the intestinal epithelial barrier and macromolecular permeability induced by pathogens.…”

“…The research showed that HMOs could prevent changes in the integrity of the intestinal epithelial barrier and macromolecular permeability induced by pathogens. After exposure to different HMOs, the host cell signal transduction response and the expression of innate and adaptive immune responses were different . HMOs can also regulate chemical barriers composed of mucus layers.…”