Do Human Milk Oligosaccharides Protect Against Infant Atopic Disorders and Food Allergy?

Abstract

Atopic disorders (AD), often coexistent with food allergy (FA), start developing in early life and have lifelong health consequences. Breastfeeding is thought to be protective against AD and FA, but the data are controversial, and mechanisms are not well understood. Human milk oligosaccharides (HMOs) are complex carbohydrates that are abundant in human milk. These are thought to contribute to the development of the infant immune system by (i) promoting healthy microbiome, (ii) inhibiting pathogen binding to gut mucosa and (iii) modulating the immune system. Differences in microbiome composition between allergic and healthy infants have been observed, regardless of breastfeeding history. To date, limited studies have examined the preventive effects of HMOs on AD and FA in infants and current data relies on observation studies as trials of varying HMO intake through randomising individuals to breastfeeding are unethical. There is evidence for beneficial effects of breastfeeding on lowering the risks of FA, eczema and asthma but there are inconsistencies amongst studies in the duration of breastfeeding, diagnostic criteria for AD and the age at which the outcome was assessed. Furthermore, current analytical methods primarily used today only allow detection of 16–20 major HMOs while more than 100 types have been identified. More large-scale longitudinal studies are required to investigate the role of HMO composition and the impact of changes over the lactation period in preventing AD and FA later in life.

Toward Sequencing the Human Milk Glycome: High-Resolution Cyclic Ion Mobility Separations of Core Human Milk Oligosaccharide Building Blocks

“…While our initial efforts focused on core structures containing the sialylation and fucosylation modifications, we also wanted to explore specific building blocks used to construct more extended lactosamine chains ( i.e. , ones with β1,3, β1,4, and β1,6 linkages) as well as galactosyllactoses, which are present in the colostrum. , We would like to reiterate that the lactosamine structures analyzed here are not present in their free form in human milk but rather represent core building blocks present in larger HMOs Figure A shows the cIMS–MS separation of three lactosamine isomers [Gal­(β1,3)­GlcNAc, Gal­(β1,4)­GlcNAc, and Gal­(β1,6)­GlcNAc] as their [M + Na] + adducts.…”

“…HMOs are the third most abundant component of human milk (after protein and fat) and have a myriad of biological roles. − Specifically, they have been implicated for promoting the healthy development of the brain, immune system, and gut microbiome of an infant but are not readily incorporated into infant formula. − Interestingly, HMOs are indigestible by infants; instead, they have been shown to have prebiotic function and mimic the natural attachment sites of harmful bacteria, thus protecting the gut microbiome and immune system of the neonate. ,− HMO production is dynamic and individualized for a given infant, where specific oligosaccharides are produced depending on the growth, food allergies, and/or diseases ( e.g. , asthma or eczema). , …”

Contribution of Gut Microbiota to Immune Tolerance in Infants

“…The lack of research on exclusively breastfed children under 6 months is striking, while the main recommendation is of this being a protective factor and an immune mediator [ 108 ], in addition to providing FOS/GOS as a part of its nutritional composition [ 109 ]. Although the studies carried out have not evidenced adverse effects or tolerance to supplementation, more robust evidence is needed to support the use of prebiotics and probiotics as a general recommendation.…”

Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort

“…However, there are also other studies demonstrating that there is even in increased risk on (mild) allergic diseases when children are being breastfed [25][26][27]. It is particularly hard to evaluate the effect of breastfeeding on the development of allergic diseases, as different definitions are used for allergic disease and different comparisons in duration of lactation [28]. Since the composition of breastfeeding is variable, it may well be that only some components in breastfeeding are protective against allergic diseases and not breastfeeding itself [28].…”

“…It is particularly hard to evaluate the effect of breastfeeding on the development of allergic diseases, as different definitions are used for allergic disease and different comparisons in duration of lactation [ 28 ]. Since the composition of breastfeeding is variable, it may well be that only some components in breastfeeding are protective against allergic diseases and not breastfeeding itself [ 28 ]. This hypothesis is supported by the findings of Lodge et al where groups of human milk oligosaccharide (HMOs) were associated with an increased or reduced change of allergic diseases development in infants [ 29 ].…”