An Expert Panel Statement on the Beneficial Effects of Human Milk Oligosaccharides (HMOs) in Early Life and Potential Utility of HMO-Supplemented Infant Formula in Cow’s Milk Protein Allergy

Abstract

This review by pediatric gastroenterology and allergy-immunology experts aimed to address the biological roles of human milk oligosaccharides (HMOs) and the potential utility of HMOs in prevention of allergy with particular emphasis on cow ’ s milk protein allergy (CMPA). The participating experts consider HMOs amongst the most critical bioactive components of human milk, which act as antimicrobials and antivirals by preventing pathogen adhesion to epithelial cells, as intestinal epithelial cell modulators by enhancing maturation of intestinal mucosa and intestinal epithelial barrier function, as prebiotics by promoting healthy microbiota composition and as immunomodulators by modulating immune cells indirectly and directly. Accordingly, the participating experts consider the proposed link between HMOs and prevention of allergy to be primarily based on the impact of HMO on gut microbiota, intestinal mucosal barrier, immunomodulation and immune maturation. Along with the lower risk of respiratory and gastrointestinal infections, HMO-supplemented formulas seem to be promising alternatives in the management of CMPA. Nonetheless, the effects of individual as well as complex mixtures of HMO in terms of clear clinical and immunological effects and tolerance development need to be further explored to fully realize the immunomodulatory mechanisms and the potential for HMOs in prevention of allergic diseases and CMPA.

Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt + Treg cell-mediated immune tolerance in neonates

“… 32 , 33 HMOs promote a healthy microbial composition and enhance intestinal mucosal maturation and the epithelial barrier function to modulate immune functions in offspring. 34 , 35 GDM is associated with a high prevalence of allergic diseases in offspring. 3–5 It alters the glycosylation pattern of N-glycans in human milk, and thus affects the gut microbiota composition of offspring.…”

Lactobacillus rhamnosus Probio-M9 alleviates OVA-sensitized food allergy through modulating gut microbiota and its metabolism

“…30 Numerous studies have shown that the specific HMO composition of HM could protect infants against food allergies. 31,32 In contrast, fewer studies have demonstrated the Food & Function Paper effect of HM probiotics on allergic reactions. Recent research has supported the promise of probiotics for preventing food allergy in the murine model of OVA-sensitization, which was used as described previously.…”

Pre-, pro-, syn-, and Postbiotics in Infant Formulas: What Are the Immune Benefits for Infants?

“…HMOs are the third most prevalent component of human milk, after lactose and lipids [44]. They are indigestible carbohydrates that selectively stimulate the colonic growth of HMO-consuming bacteria, including Bifidobacteria [45,46]. More than 200 different HMOs have been identified in human milk, with up to 130 for an individual mother.…”

“…HMO composition is highly influenced by the genetic status of the mother, i.e., secretor and Lewis statuses determining the expressions of FUT2 and FUT3 fucosyltransferases, respectively. As a result of FUT2 activity, 2'-fucosyllactose (2'FL) is the most abundant HMO in breastmilk from secretor mothers (70-90% depending on country), representing 20-40% of the total HMO concentration in colostrum [45]. HMOs promote intestinal barrier function, prevent adhesion of pathogens to epithelial cells, act as decoy receptors, and stimulate the development of an infant's immune system either directly or through a microbiotamediated effect [47].…”