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

Richard Y Wu,Eva Landberg,Thomas R Abrahamsson,Steven R Botts,Philip M Sherman,Kathene C Johnson-Henry

doi:10.3390/nu14051014

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.

Highlights

human milk oligosaccharides (HMOs) serve as receptor analogues to the block binding of enteric pathogens and their toxins to mucosal surfaces [5,6] and can directly activate cell surface receptors to influence various functions of the intestinal epithelial barrier [7]
The dextran flux assay showed that Escherichia coli (EHEC)-induced increases in macromolecule permeability were reduced in polarized epithelia pretreated with HMOs. These results indicate that individual HMO blends share barrier-protective properties, regardless of composition, but vary in their ability to protect against bacterial pathogen-induced disruption in the localization of intercellular tight junction proteins
O157:H7 challenge, claudin-1 was preserved only in cells treated with HMOs prepared from individuals 3 and 4 (Figure 3F). These results demonstrate that while individual HMO blends share similar effects on mRNA expression of two intercellular tight junction proteins, there is variability in how HMOs prepared from different mothers preserve ZO-1 and claudin-1 protein expression in response to intestinal injury following challenge with EHEC O157:H7

Summary

Introduction

Human milk is the gold standard for infant nutrition up to six months of age [1,2].Human milk provides essential micro- and macronutrients, and contains a plethora of bioactive compounds [1]. Following carbohydrate lactose and lipids, human milk oligosaccharides (HMOs) constitute the third most abundant component of mature human milk in concentrations between 5 and 15 g/L [3]. Activate cell surface receptors to influence various functions of the intestinal epithelial barrier [7]. Unlike plant-derived glycans or animal sources of milk oligosaccharides, HMOs are highly complex oligosaccharides notable for marked variability, with up to 150 structures that differ between lactating individuals [8]. 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. 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

Methods

Results

Discussion

Conclusion