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• W4383982108 abstract "Recent findings from infant cohort, animal, and in vitro studies suggest that human milk oligosaccharides (HMOs) found in breastmilk exhibit allergy-protective effects.Maternal HMO composition varies widely; thus, the allergy-protective efficacy of HMOs depends on complex interactions between multiple factors, including maternal secretor status, infant risk status, geographical location, and allergy phenotype.Individual HMOs have structure-specific immunological actions in the prevention of various allergies.Aside from the prebiotic effects on the intestinal microbiome, HMOs influence early-life immune programming, including mediating antigen-presenting cell activation and T helper cell balance, contributing to possible allergy-protective benefits.The presumed allergy-protective properties of HMOs likely reflect multiple direct and indirect mechanisms, including modifications of intestinal microbiomes, epithelial barrier maturation, immunomodulation, and regulation of inflammation-associated genes. Emerging research suggests that human milk oligosaccharides (HMOs) found in breastmilk can reduce allergy susceptibility in early life through modification of the intestinal microbiome, strengthening intestinal barrier integrity, and immunomodulation. This has significant implications in the development of HMO-based and microbiota-targeted interventions as putative novel treatments for childhood allergy prevention. HMOs, glycans found in breastmilk, have powerful immunomodulatory properties and represent an exciting means to aid in the prevention of childhood allergy. Atopy, an exaggerated IgE immune response to an external antigen, affects one in five individuals worldwide [1.Bantz S.K. et al.The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma.J. Clin. Cell. Immunol. 2014; 5: 67-73Google Scholar]. The prevalence of childhood allergy, including asthma, atopic dermatitis, and food allergy, has drastically increased in recent years, with 20% of children worldwide reported to present with atopic dermatitis [2.Nutten S. Atopic dermatitis: global epidemiology and risk factors.Ann. Nutr. Metab. 2015; 66: 8-16Crossref PubMed Scopus (649) Google Scholar] and 8–10% with asthma [3.Asher M.I. et al.Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study.Lancet. 2021; 398: 1569-1580Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar], significantly impacting quality of life. Pediatric food allergy alone costs the USA $25 billion annually [4.Gupta R. et al.The economic impact of childhood food allergy in the United States.JAMA Pediatr. 2013; 167: 1026-1031Crossref PubMed Scopus (320) Google Scholar], representing a major economic and health burden. Unfortunately, preventive strategies are lacking, with most of the emphasis on treating symptoms. While acknowledging the multifactorial nature of allergic diseases and that there is no singular intervention to effectively tackle them universally, determining the efficacy of novel allergy-preventive measures is vital to help reduce allergy prevalence worldwide. Early-life is a crucial phase in allergy development as the infant immune system and intestinal microbiota undergo marked development, with the first 1000 days of life thought to be a critical window in which external factors, including nutrition, are most influential on long-term immune programming [5.Cukrowska B. Microbial and nutritional programming—the importance of the microbiome and early exposure to potential food allergens in the development of allergies.Nutrients. 2018; 10: 1541Crossref PubMed Scopus (15) Google Scholar,6.Romano-Keeler J. Sun J. The first 1000 days: assembly of the neonatal microbiome and its impact on health outcomes.Newborn. 2022; 1: 219-226Crossref Google Scholar]. Accordingly, emerging research suggests that HMOs found in breastmilk may have a potential therapeutic role against infant allergy [7.Miliku K. et al.Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study.Allergy. 2018; 73: 2070-2073Crossref PubMed Scopus (44) Google Scholar,8.Castillo-Courtade L. et al.Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.Allergy. 2015; 70: 1091-1102Crossref PubMed Google Scholar]. HMOs are complex glycans comprising glucose, galactose, fucose, sialic acid, and N-acetylglucosamine, collectively making up the third most abundant component of breastmilk [9.Bode L. The functional biology of human milk oligosaccharides.Early Hum. Dev. 2015; 91: 619-622Crossref PubMed Scopus (295) Google Scholar]. Over 200 structurally distinct HMOs have been identified to date [10.Ruhaak L.R. Lebrilla C.B. Advances in analysis of human milk oligosaccharides.Adv. Nutr. 2012; 3: 406S-414SAbstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar], broadly categorized into three structural groups (Table 1). Notably, the HMO profile of breastmilk varies significantly between mothers, reflecting numerous maternal factors, including secretor status (see Glossary), genetics, geographical location, diet, and body mass index [11.Han S.M. et al.Maternal and infant factors influencing human milk oligosaccharide composition: beyond maternal genetics.J. Nutr. 2021; 151: 1383-1393Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,12.Seferovic M.D. et al.Maternal diet alters human milk oligosaccharide composition with implications for the milk metagenome.Sci. Rep. 2020; 10: 1-18Crossref PubMed Scopus (0) Google Scholar]. In particular, maternal secretor status, Lewis blood type, as well as whether blood group antigens are secreted into bodily fluids, are determined by two gene loci: the secretor gene encoding α1-2-fucosyltransferase (FUT2) and the Lewis gene encoding α1-3/4-fucosyltransferase (FUT3), which largely influence HMO composition [13.Lefebvre G. et al.Time of lactation and maternal fucosyltransferase genetic polymorphisms determine the variability in human milk oligosaccharides.Front. Nutr. 2020; 7574459Crossref PubMed Scopus (32) Google Scholar] (Table 2). Moreover, both the concentration and composition of HMOs fluctuate throughout lactation, with an average HMO concentration in colostrum of 20–25 g/l, decreasing to 10–13 g/l in mature milk [14.Soyyılmaz B. et al.The mean of milk: a review of human milk oligosaccharide concentrations throughout lactation.Nutrients. 2021; 13: 2737Crossref PubMed Scopus (48) Google Scholar,15.Plows J.F. Longitudinal changes in human milk oligosaccharides (HMOs) over the course of 24 months of lactation.J. Nutr. 2021; 151: 876-882Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. Such diversity in HMO composition is noteworthy as certain HMO profiles correlate with reduced allergy risk [8.Castillo-Courtade L. et al.Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.Allergy. 2015; 70: 1091-1102Crossref PubMed Google Scholar,16.Lodge C.J. et al.Human milk oligosaccharide profiles and allergic disease up to 18 years.J. Allergy Clin. Immunol. 2021; 147: 1041-1048Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,17.Sprenger N. et al.FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk.Eur. J. Nutr. 2017; 56: 1293-1301Crossref PubMed Scopus (77) Google Scholar].Table 1Structural classification of HMOs [9.Bode L. The functional biology of human milk oligosaccharides.Early Hum. Dev. 2015; 91: 619-622Crossref PubMed Scopus (295) Google Scholar]aAbbreviations: 2′FL, 2′-fucosyllactose; 3′FL, 3′-fucosyllactose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetraose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.HMO structureExamplesProportion of known HMOsNeutral non-fucosylated (N-containing)LNT, LNnT40–55%Neutral fucosylated2′FL, 3′FL35–50%Acidic sialylated3′SL, 6′SL10–14%a Abbreviations: 2′FL, 2′-fucosyllactose; 3′FL, 3′-fucosyllactose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetraose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose. Open table in a new tab Table 2HMO profiles based on maternal secretor and Lewis status, and average percentage of women expressing each genotype worldwide [14.Soyyılmaz B. et al.The mean of milk: a review of human milk oligosaccharide concentrations throughout lactation.Nutrients. 2021; 13: 2737Crossref PubMed Scopus (48) Google Scholar]aAbbreviations: 2′FL, 2′-fucosyllactose; 3′FL, 3′-fucosyllactose; FUT2, α1-2-fucosyltransferase; FUT3, α1-3/4-fucosyltransferase; LNFP-I, lacto-N-fucopentaose I; LNFP-II, lacto-N-fucopentaose II; LNFP-III, lacto-N-fucopentaose III; LNFP-V, lacto-N-fucopentaose V.GeneLewis positive (le+) FUT3 functionalLewis negative (le–) FUT3 inactiveSecretor positive (se+) FUT2 functionalAll HMOs(70% of population)2′FL, LNFP-I, 3′FL, LNFP-II, LNFP-III(9% of population)Secretor negative (se–) FUT2 inactive3′FL, LNFP-II, LNFP-III(20% of population)3′FL, LNFP-III, LNFP-V(1% of population)a Abbreviations: 2′FL, 2′-fucosyllactose; 3′FL, 3′-fucosyllactose; FUT2, α1-2-fucosyltransferase; FUT3, α1-3/4-fucosyltransferase; LNFP-I, lacto-N-fucopentaose I; LNFP-II, lacto-N-fucopentaose II; LNFP-III, lacto-N-fucopentaose III; LNFP-V, lacto-N-fucopentaose V. Open table in a new tab Accordingly, an increasing body of research, including observational studies [7.Miliku K. et al.Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study.Allergy. 2018; 73: 2070-2073Crossref PubMed Scopus (44) Google Scholar], animal models [8.Castillo-Courtade L. et al.Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.Allergy. 2015; 70: 1091-1102Crossref PubMed Google Scholar], and in vitro data [18.Zehra S. et al.Human milk oligosaccharides attenuate antigen–antibody complex induced chemokine release from human intestinal epithelial cell lines.J. Food Sci. 2018; 83: 499-508Crossref PubMed Scopus (38) Google Scholar], suggests that HMOs may provide allergy-protective effects. However, many current findings are varied, unorganized, and lack robustness, making it difficult to draw conclusions on the roles of HMOs in allergic conditions. Given the increasing global allergy prevalence [19.Loh W. Tang M.L. The epidemiology of food allergy in the global context.Int. J. Environ. Res. Public Health. 2018; 15: 2043Crossref PubMed Scopus (256) Google Scholar,20.Spolidoro G.C. et al.Frequency of food allergy in Europe: an updated systematic review and meta-analysis.Allergy. 2023; 78: 351-368Crossref PubMed Scopus (0) Google Scholar], the need for effective interventions is considerable. Thus, harnessing HMOs as putative and complementary therapeutic tools has valuable clinical significance as well as industry implications for the development of specialized formula milk, with anticipated economic benefits in reducing the financial burden of allergy worldwide. Therefore, this review examines the current literature, evaluates possible underlying mechanisms of HMOs in allergic diseases, assesses limitations in the field, and discusses future research directions to ultimately enable HMOs as potential therapeutics for reducing childhood allergy prevalence. To date, several epidemiological studies have reported associations between HMO profile (both composition and concentration) and offspring allergy risk. For instance, in a cohort of 70 infants aged 0–6 months, high concentrations of lacto-N-fucopentaose III (LNFP-III), compared with low, correlated with reduced risk of cow’s milk allergy (CMA) at 6 months (manifested as vomiting, diarrhea, wheezing, cough, urticaria, or atopic dermatitis following milk consumption). This suggested that Lewis-dependent HMOs might play a protective role against CMA [21.Seppo A.E. et al.Human milk oligosaccharides and development of cow’s milk allergy in infants.J. Allergy Clin. Immunol. 2017; 139: 708-711Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar]. In contrast, in 421 mother-child dyads from the Canadian Healthy Infant Longitudinal Development study (https://childstudy.ca), breastmilk concentrations of fucosyl-disialyllacto-N-hexose (FDSLNH), lacto-N-fucopentaose I (LNFP-I), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose II (LNFP-II), sialyllacto-N-tetraose c (LSTc), and fucosyllacto-N-hexaose (FLNH) negatively correlated with risk of food sensitization at 1 year; by contrast, higher concentrations of lacto-N-hexaose (LNH), lacto-N-tetraose (LNT), 2′-fucosyllactose (2′FL), and disialyl-lacto-N-hexaose (DSLNH) were associated with an increased risk of food sensitization [8.Castillo-Courtade L. et al.Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.Allergy. 2015; 70: 1091-1102Crossref PubMed Google Scholar]. However, opposing the aforementioned study, no individual HMOs alone correlated with food sensitization. This suggests that the overall combination of HMOs rather than individual structures may be important for protection against food allergy, reflecting the existence of over 200 HMOs in breastmilk. Thus, supplementing infant formula with a synergistic mixture of HMOs may prove to be more effective against allergy than single HMOs alone. However, future studies are needed to fully validate this conclusion. Noteworthy, a recent study of high-risk infants followed to age 18 years demonstrated that acidic Lewis-dependent HMOs were associated with higher eczema, wheeze, and asthma risk throughout childhood [16.Lodge C.J. et al.Human milk oligosaccharide profiles and allergic disease up to 18 years.J. Allergy Clin. Immunol. 2021; 147: 1041-1048Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. However, risk of food sensitization negatively correlated with acidic HMOs, suggesting that the protective effects of various HMO groups may differ depending on atopic disease. Additionally, one group [21.Seppo A.E. et al.Human milk oligosaccharides and development of cow’s milk allergy in infants.J. Allergy Clin. Immunol. 2017; 139: 708-711Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar] reported that infants (aged 0–6 months) with delayed-onset CMA had mothers who were secretors; thus, infants consumed FUT2-dependent HMOs, whereas mothers of infants with immediate IgE-mediated CMA were all nonsecretors. These findings suggest that maternal secretor status may influence the endotype of allergy developed, emphasizing the complex relationship between HMO composition and allergy. Hence, future research should identify distinct HMOs that reduce susceptibility to varying allergy endotypes, rather than assuming they provide protection against all atopic diseases simultaneously. Moreover, the protective efficacy of HMOs may depend on infant risk status. One group reported that infants born via cesarean section had higher allergy susceptibility than those vaginally delivered; yet, when the former were exposed to FUT2-dependent HMOs, their risk of developing IgE-mediated eczema at 2 years, but not 5 years, was reduced [17.Sprenger N. et al.FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk.Eur. J. Nutr. 2017; 56: 1293-1301Crossref PubMed Scopus (77) Google Scholar]. Notably, this association was only present for cesarean-delivered infants (who suffer microbiome perturbations [22.Kim G. et al.Delayed establishment of gut microbiota in infants delivered by cesarean section.Front. Microbiol. 2020; 11: 2099Crossref PubMed Scopus (30) Google Scholar]), suggesting the allergy-protective effects of HMOs may only apply to high-risk infants and depend on complex interactions between several factors. Despite this, further research is necessary to validate these findings in a larger cohort, particularly as HMOs’ protective associations were only found in a limited subset of infants. In contrast, other studies have not found such promising associations between HMO consumption and allergy. In an observational study of Swedish infants, breastmilk HMO composition showed no association with infant allergy risk up to 18 months of age [23.Sjögren Y.M. et al.Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age.Pediatr. Allergy Immunol. 2007; 18: 20-26Crossref PubMed Scopus (33) Google Scholar], questioning the HMO allergy-protective potential. However, this study was limited by sample size (n = 20) and only nine neutral HMOs were assessed, reducing the validity of these findings. Taken together, epidemiological studies (Table 3) suggest that HMOs play a protective role against early-life allergy, yet this depends on HMO structure, infant risk status, maternal secretor status, and allergy type. Despite these promising findings, which are only correlational, many factors are at play that impact the complex relationship between HMOs and allergy.Table 3Summary of studies herein relating to the potential allergy-protective and immunomodulatory effects of HMOsaAbbreviations: CXCL1, CXCL2, and CXCL3, C-X-C motif chemokine ligands 1, 2, and 3; DC, dendritic cells; DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyl-lacto-N-hexaose; FDSLNH, fucosyl-disialyllacto-N-hexose; 2′FL, 2′-fucosyllactose; FLNH, fucosyllacto-N-hexaose; FUT2, α1-2-fucosyltransferase; LNFP-I, lacto-N-fucopentaose I; LNFP-II, lacto-N-fucopentaose II; LNFP III, lacto-N-fucopentaose III; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetraose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyllacto-N-tetraose c; miR-146a, miRNA 146a; MMCP-1, mucosal mast cell protease-1; MUC2, mucin 2; OVA, ovalbumin allergen; ROS, reactive oxygen species; TFF3, Trefoil factor.ModelHMO treatmentOutcomeRefsMurine modelMurine model of necrotizing enterocolitisCaco-2 and LS174T intestinal epithelial cellsHMOs isolated from pooled breastmilkHMO treatment upregulated MUC2 and TFF3 expression in Caco-2 cells, suggesting increased mucus production.HMO supplementation reduced intestinal permeability and increased MUC2 in a murine model of necrotizing enterocolitis.[89.Wu R.Y. et al.Human milk oligosaccharides increase mucin expression in experimental necrotizing enterocolitis.Mol. Nutr. Food Res. 2019; 631800658Google Scholar]OVA-induced murine model of food allergy.Bone marrow-derived mast cells (BMMCs) from sensitized mice2′FL, 6′SLBoth 2′FL and 6′SL reduced food allergy symptoms (diarrhea and hypothermia), increased Treg numbers in Peyer’s patches, and suppressed intestinal MMCP-1 and mast cell numbers in the murine model.In vitro, 6′SL inhibited degranulation of sensitized murine BMMCs.[8.Castillo-Courtade L. et al.Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.Allergy. 2015; 70: 1091-1102Crossref PubMed Google Scholar]β-Lactoglobulin-induced murine model of cow’s milk allergy (CMA).β-Lactoglobulin-sensitized murine macrophage RAW 264.7 cells2'FL and HMOs isolated from pooled breastmilkBoth 2′FL and pooled HMO treatment reduced β-lactoglobulin-IgE, mast cell degranulation, TNF-α, IL-4, and IL-6; increased miR-146a expression in vivo.In vitro, 2′FL and pooled HMOs decreased ROS, nitric oxide release, and proinflammatory cytokines from sensitized RAW 264.7 murine macrophage cells.2′FL and pooled HMO inhibited activation of the TLR4/NFκB inflammatory pathway and upregulated miR-146a expression in RAW 264.7 cells.[111.Li A. et al.The human milk oligosaccharide 2′-fucosyllactose attenuates β-lactoglobulin–induced food allergy through the miR-146a–mediated toll-like receptor 4/nuclear factor-κB signaling pathway.J. Dairy Sci. 2021; 104: 10473-10484Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]In vitroCaco-2 intestinal epithelial cellsHMOs isolated from pooled breastmilkBifidobacterium breve and Bifidobacterium infantis grown on HMO-supplemented media significantly downregulated chemokine-associated genes in Caco-2 cells, including CXCL1, CXCL2, and CXCL3, compared with Bifidobacterium grown on lactose and glucose.[50.Wickramasinghe S. et al.Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells.BMC Microbiol. 2015; 15: 1-12Crossref PubMed Scopus (60) Google Scholar]Caco-2 intestinal epithelial cellsPooled galacto-oligosaccharides (GOS) from lactoseGOS treatment strengthened tight junctions in deoxynivalenol-damaged Caco-2 cells and prevented loss of epithelial barrier function, measured by transepithelial electrical resistance (TEER) and markers of intestinal permeability.[90.Akbari P. et al.Galacto-oligosaccharides protect the intestinal barrier by maintaining the tight junction network and modulating the inflammatory responses after a challenge with the mycotoxin deoxynivalenol in human Caco-2 cell monolayers and B6C3F1 mice.J. Nutr. 2015; 145: 1604-1613Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar]Caco-2 intestinal epithelial cells3′-Galactosyllactose (3′GL)3′GL with a β1–3 glycosidic linkage protected Caco-2 cells from deoxynivalenol-induced damage, whereas 3′GL with an α1–3 glycosidic linkage did not, as measured by TEER.[91.Varasteh S. et al.Human milk oligosaccharide 3′-galactosyllactose can protect the intestinal barrier to challenges.J. Pediatr. Gastroenterol. Nutr. 2019; 68 (N-P-016:1049)Google Scholar]Human monocyte-derived dendritic cellsCD4+ naive T cellsHMOs isolated from pooled breastmilkHMO treatment increased production of IL-10 and IL-27, but not TNF-α or IL-6 from dendritic cells. During co-culture, HMO-treated DCs stimulated the production of Tregs and IL-10 from naive T cells, while decreasing Th1 and IFN-γ.[96.Xiao L. et al.Human milk oligosaccharides promote immune tolerance via direct interactions with human dendritic cells.Eur. J. Immunol. 2019; 49: 1001-1014Crossref PubMed Scopus (56) Google Scholar]Electrospray ionization mass spectrometry (ESI-MS)32 pure HMOsUsing ESI-MS, 25 of 32 HMOs bound to all four human galectin proteins assessed: hGal-1, hGal-3, hGal-7, hGal-9.[97.Shams-Ud-Doha K. et al.Human milk oligosaccharide specificities of human galectins. Comparison of electrospray ionization mass spectrometry and glycan microarray screening results.Anal. Chem. 2017; 89: 4914-4921Crossref PubMed Scopus (31) Google Scholar]Shotgun glycan microarray (SGM) analysisPre-existing database of 247 HMOs in a SGM libraryDC-SIGN lectin (found on dendritic cells) showed robust binding to most HMOs, including 2′FL and 3′FL, as measured by flow cytometry.Siglec-5 and Siglec-9 lectins showed weak, but present, binding to sialylated HMO structures.[98.Noll A.J. et al.Human DC-SIGN binds specific human milk glycans.Biochem. J. 2016; 473: 1343-1353Crossref PubMed Scopus (54) Google Scholar]Cord blood mononuclear cells (CBMCs) from healthy neonatesPooled HMOs grouped into either acidic or neutral HMOsAcidic HMO treatment increased production of IFN- γ and IL-10 and decreased IL-13 from human CBMCs[101.Eiwegger T. et al.Human milk–derived oligosaccharides and plant-derived oligosaccharides stimulate cytokine production of cord blood T-cells in vitro.Pediatr. Res. 2004; 56: 536-540Crossref PubMed Scopus (171) Google Scholar]T-84 and HT-29 intestinal epithelial cells2′FL and 6′SL2′FL and 6′SL treatment inhibited the release of CCL20 and IL-8 chemokines from T-84 and HT-29 intestinal epithelial cells stimulated with an antigen–antibody complex (model of food allergy). 2′FL suppressed chemokine release through NFκB inhibition; 6′SL acted through inhibition of AP-1 signaling.[18.Zehra S. et al.Human milk oligosaccharides attenuate antigen–antibody complex induced chemokine release from human intestinal epithelial cell lines.J. Food Sci. 2018; 83: 499-508Crossref PubMed Scopus (38) Google Scholar]HT-29 colonic epithelial cellsPooled HMOs, bovine colostrum oligosaccharides (BCOs) and 3′GLHMOs and BCOs influenced the expression of several immune-associated glycogenes, including cytokine, chemokine, and cell surface receptor genes such as those encoding CXCL3, CXCL1, CXCL2, CXCL6, IL-17C, GM-CSF2, IL-8, IL-1β. HMOs upregulated IL-17c and IL-1β expression.[116.Lane J.A. et al.Transcriptional response of HT-29 intestinal epithelial cells to human and bovine milk oligosaccharides.Br. J. Nutr. 2013; 110: 2127-2137Crossref PubMed Scopus (0) Google Scholar]Human observational studies70 Mother–child dyadsInfants aged 0–6 monthsHMOs present in human breastmilkLow breastmilk concentrations of LNFP-II were associated with increased risk of CMA at 6 months, compared with higher LNFP-II concentrations. The mothers of infants who developed delayed-onset CMA were all secretors (FUT2-dependent), whereas those who developed IgE-mediated CMA had nonsecretor mothers.[21.Seppo A.E. et al.Human milk oligosaccharides and development of cow’s milk allergy in infants.J. Allergy Clin. Immunol. 2017; 139: 708-711Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar]421 Mother–child dyads from CHILD Cohort study.Assessed at 1 yearHMOs present in human breastmilkHigh concentration of FDSLNH, LNFP-I, LNnT, LNFP-II, LSTc, and FLNH was associated with a decreased risk of food sensitization at 1 year of age, whereas high concentrations of LNH, LNT, 2′FL, and DSLNH were associated with an increased risk.[7.Miliku K. et al.Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study.Allergy. 2018; 73: 2070-2073Crossref PubMed Scopus (44) Google Scholar]285 Mother–child dyads of high-risk infants. Followed till 18 years oldHMOs present in human breastmilkNeutral and acidic Lewis HMOs were associated with increased risk of allergy and asthma throughout childhood, whereas acidic HMOs were associated with decreased risk of food sensitization.[16.Lodge C.J. et al.Human milk oligosaccharide profiles and allergic disease up to 18 years.J. Allergy Clin. Immunol. 2021; 147: 1041-1048Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]226 Mother–child dyads of high-risk infants. Assessed at 2 and 5 years oldHMOs present in human breastmilkFUT2-dependent HMOs were associated with increased risk of allergy in infants born via caesarean section.Infants born via caesarean-section had a higher allergy risk, yet FUT2-dependent HMOs reduced eczema risk at 2 years, but not 5 years.[17.Sprenger N. et al.FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk.Eur. J. Nutr. 2017; 56: 1293-1301Crossref PubMed Scopus (77) Google Scholar]20 Mother–child dyads, from 6 to 18 months oldHMOs present in human breastmilkNo association found between breastmilk concentration of nine neutral HMOs and allergy risk up to 18 months old.[23.Sjögren Y.M. et al.Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age.Pediatr. Allergy Immunol. 2007; 18: 20-26Crossref PubMed Scopus (33) Google Scholar]33 InfantsBreastfed n = 17Formula-fed n = 16HMOs present in human breastmilkHMOs in plasma and urine of breastfed infants correlated with concentrations in milk, indicating HMO absorption.Plasma and urine HMO concentrations were low: 0.1% milk in plasma and 4% milk in urine.[25.Goehring K.C. et al.Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants.PLoS One. 2014; 9e101692Crossref PubMed Scopus (168) Google Scholar]56 Mother–child dyads.Followed from day 6 to 6 months of ageHMOs present in human breastmilkHMO composition correlated with infant fecal microbiome: concentration of fucosylated HMOs correlated with fecal Bifidobacterium abundance and N-glycans correlated with Lactobacillus abundance. Infants with secretor mothers showed increased intestinal expression of genes encoding glycosyl transferases and ATP-binding cassette transporters, compared with those with nonsecretor mothers, indicating functional differences in microbial genomes based on secretor status.[61.Bai Y. et al.Fucosylated human milk oligosaccharides and N-glycans in the milk of Chinese mothers regulate the gut microbiome of their breast-fed infants during different lactation stages.mSystems. 2018; 3e00206-18Crossref PubMed Google Scholar]10 Mother–child dyadsFollowed from day 2 to 4 months of ageHMOs present in human breastmilkInfant oral and fecal microbiome correlated with HMO composition of breastmilk. Higher intake of LNT, LNnT, LNFP-I, LNFP-II, LNFP-III, LSTb, DFLNT, FLNH, LNH, DFLNH positively associated with Enterococcus sp., Parabacteroides sp., and Bifidobacterium sp. abundance. Both breastmilk HMO composition and infant microbiome, and their correlations, varied over time.[62.Cheema A.S. et al.Exclusively breastfed infant microbiota develops over time and is associated with human milk oligosaccharide intakes.Int. J. Mol. Sci. 2022; 23: 2804Crossref PubMed Scopus (0) Google Scholar]93 Mother–child dyadsFollowed from 0 to 2 yearsHMOs present in human breastmilkHigher LNF-I and 2′FL to LNF-II and 3′FL ratio was associated with decreased risk of diarrhea in infants.[103.Newburg D.S. et al.Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants.Glycobiology. 2004; 14: 253-263Crossref PubMed Scopus (208) Google Scholar]a Abbreviations: CXCL1, CXCL2, and CXCL3, C-X-C motif chemokine ligands 1, 2, and 3; DC, dendritic cells; DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyll" @default.
• W4383982108 created "2023-07-12" @default.
• W4383982108 creator A5024029262 @default.
• W4383982108 creator A5084287138 @default.
• W4383982108 date "2023-08-01" @default.
• W4383982108 modified "2023-10-16" @default.
• W4383982108 title "Human milk oligosaccharides: potential therapeutic aids for allergic diseases" @default.
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