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FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk

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Abstract

Purpose

Manifestation of allergic disease depends on genetic predisposition, diet and commensal microbiota. Genetic polymorphism of mothers determines their breast milk glycan composition. One major determinant is the fucosyltransferase 2 (FUT2, secretor gene) that was shown to be linked to commensal microbiota establishment. We studied whether FUT2-dependent breast milk oligosaccharides are associated with allergic disease in breast-fed infants later in life.

Methods

We analyzed FUT2-dependent oligosaccharides in breast milk samples of mothers (n = 266) from the placebo group of a randomized placebo-controlled trial of prebiotics and probiotics as preventive against allergic disease in infants with high allergy risk (trial registry number: NCT00298337). Using logistic regression models, we studied associations between FUT2-dependent breast milk oligosaccharides and incidence of allergic disease at 2 and 5 years of age.

Results

At 2 years, but not at 5 years of age, we observed a presumed lower incidence (p < 0.1) for IgE-associated eczema manifestation in C-section-born infants who were fed breast milk containing FUT2-dependent oligosaccharides. By logistic regression, we observed a similar relation (p < 0.1) between presence of FUT2-dependent breast milk oligosaccharides and IgE-associated disease and IgE-associated eczema in C-section-born infants only. When testing with the levels of breast milk oligosaccharide 2′-fucosyllactose as proxy for FUT2 activity, we observed significant (p < 0.05) associations in the C-section-born infants with ‘any allergic disease,’ IgE-associated disease, eczema and IgE-associated eczema.

Conclusion

The data indicate that infants born by C-section and having a high hereditary risk for allergies might have a lower risk to manifest IgE-associated eczema at 2 years, but not 5 years of age, when fed breast milk with FUT2-dependent milk oligosaccharides. Further studies with larger cohorts and especially randomized controlled intervention trials are required to build on these preliminary observations.

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References

  1. Legatzki A, Rösler B, von Mutius ME (2014) Microbiome diversity and asthma and allergy risk. Curr Allergy Asthma Rep 14:466

    Article  Google Scholar 

  2. Macfarlane GT, Macfarlane LE (2009) Acquisition, evolution and maintenance of the normal gut microbiota. Dig Dis 27(Suppl 1):90–98

    Article  Google Scholar 

  3. Mackie RI, Sghir A, Gaskins HR (1999) Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 69:1035S–1045S

    CAS  Google Scholar 

  4. Nauta AJ, Ben AK, Knol J, Garssen J, van der Beek EM (2013) Relevance of pre- and postnatal nutrition to development and interplay between the microbiota and metabolic and immune systems. Am J Clin Nutr 98:586S–593S

    Article  CAS  Google Scholar 

  5. Fouhy F, Ross RP, Fitzgerald GF, Stanton C, Cotter PD (2012) Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes 3:203–220

    Article  Google Scholar 

  6. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20:159–166

    Article  CAS  Google Scholar 

  7. Kunz C, Rudloff S, Baier W, Klein N, Strobel S (2000) Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr 20:699–722

    Article  CAS  Google Scholar 

  8. Jantscher-Krenn E, Bode L (2012) Human milk oligosaccharides and their potential benefits for the breast-fed neonate. Minerva Pediatr 64:83–99

    CAS  Google Scholar 

  9. Stahl B, Thurl S, Henker J, Siegel M, Finke B, Sawatzki G (2001) Detection of four human milk groups with respect to Lewis-blood-group-dependent oligosaccharides by serologic and chromatographic analysis. Adv Exp Med Biol 501:299–306

    Article  CAS  Google Scholar 

  10. Blank D, Dotz V, Geyer R, Kunz C (2012) Human milk oligosaccharides and Lewis blood group: individual high-throughput sample profiling to enhance conclusions from functional studies. Adv Nutr 3:440S–449S

    Article  CAS  Google Scholar 

  11. Erney RM, Malone WT, Skelding MB, Marcon AA, Kleman-Leyer KM, O’Ryan ML, Ruiz-Palacios G, Hilty MD, Pickering LK, Prieto PA (2000) Variability of human milk neutral oligosaccharides in a diverse population. J Pediatr Gastroenterol Nutr 30:181–192

    Article  CAS  Google Scholar 

  12. Castanys-Munoz E, Martin MJ, Prieto PA (2013) 2′-fucosyllactose: an abundant, genetically determined soluble glycan present in human milk. Nutr Rev 71:773–789

    Article  Google Scholar 

  13. Lewis ZT, Totten SM, Smilowitz JT, Popovic M, Parker E, Lemay DG, Van Tassell ML, Miller MJ, Jin YS, German JB, Lebrilla CB, Mills DA (2015) Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome 3:13

    Article  Google Scholar 

  14. Newburg DS, Ruiz-Palacios GM, Morrow AL (2005) Human milk glycans protect infants against enteric pathogens. Annu Rev Nutr 25:37–58

    Article  CAS  Google Scholar 

  15. Morrow AL, Ruiz-Palacios GM, Jiang X, Newburg DS (2005) Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea. J Nutr 135:1304–1307

    CAS  Google Scholar 

  16. Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios G, Pickering LK, Newburg DS (2001) Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology 11:365–372

    Article  CAS  Google Scholar 

  17. Yu ZT, Chen C, Newburg DS (2013) Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology 23:1281–1292

    Article  CAS  Google Scholar 

  18. Yu ZT, Chen C, Kling DE, Liu B, McCoy JM, Merighi M, Heidtman M, Newburg DS (2013) The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology 23:169–177

    Article  CAS  Google Scholar 

  19. Castillo-Court Han S, Lee S, Mian FM, Buck R, Forsythe P (2015) Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy 70:1091–1102

    Article  Google Scholar 

  20. Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107:129–134

    Article  CAS  Google Scholar 

  21. Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC (2012) Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 129:434–440

    Article  Google Scholar 

  22. Ismail IH, Oppedisano F, Joseph SJ, Boyle RJ, Licciardi PV, Robins-Browne RM, Tang ML (2012) Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatr Allergy Immunol 23:674–681

    Article  Google Scholar 

  23. Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le VJ, Nicholson JK, Dumas ME, Khanna KM, Mani S (2014) Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like Receptor 4. Immunity 41:296–310

    Article  CAS  Google Scholar 

  24. Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M (2007) Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 119:192–198

    Article  CAS  Google Scholar 

  25. Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E (2009) Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol 123:335–341

    Article  Google Scholar 

  26. Blank D, Gebhardt S, Maass K, Lochnit G, Dotz V, Blank J, Geyer R, Kunz C (2011) High-throughput mass finger printing and Lewis blood group assignment of human milk oligosaccharides. Anal Bioanal Chem 401:2495–2510

    Article  CAS  Google Scholar 

  27. Newburg DS, Ruiz-Palacios GM, Altaye M, Chaturvedi P, Meinzen-Derr J, Guerrero ML, Morrow AL (2004) Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants. Glycobiology 14:253–263

    Article  CAS  Google Scholar 

  28. Negele K, Heinrich J, Borte M, von Berg A, Schaaf B, Lehmann I, Wichmann HE, Bolte G (2004) Mode of delivery and development of atopic disease during the first 2 years of life. Pediatr Allergy Immunol 15:48–54

    Article  Google Scholar 

  29. Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E (2013) Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol 132:601–607

    Article  Google Scholar 

  30. Chichlowski M, De LG, German JB, Raybould HE, Mills DA (2012) Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function. J Pediatr Gastroenterol Nutr 55:321–327

    Article  CAS  Google Scholar 

  31. Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-van LM, Madsen KL (2008) Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol 295:G1025–G1034

    Article  CAS  Google Scholar 

  32. Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar N (2013) Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol 304:G132–G141

    Article  CAS  Google Scholar 

  33. Castillo-Courtade L, Han S, Lee S, Mian FM, Buck R, Forsythe P (2015) Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy 70:1091–1102

    Article  CAS  Google Scholar 

  34. Maroni L, van de Graaf SF, Hohenester SD, Oude Elferink RP, Beuers U (2014) Fucosyltransferase 2: a genetic risk factor for primary sclerosing cholangitis and Crohn’s disease—a comprehensive review. Clin Rev Allergy Immunol 48:182–191

    Article  Google Scholar 

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Acknowledgments

We thank the study participants and their parents for participation, Dr. Rajat Mukherjee for help with the statistical analysis and Drs. Aristea Binia, Carine Gaelle Blanchard, Chiara Nembrini, and Susan Wernimont for critical discussion and reviewing of the manuscript. The study got financial support from the Nestle Research Center, Nestec S.A., Switzerland.

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Correspondence to Norbert Sprenger or Clemens Kunz.

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NS and HO are employees of Nestec S.A., and CK received a research Grant from Nestec S.A.

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Sprenger, N., Odenwald, H., Kukkonen, A.K. 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 56, 1293–1301 (2017). https://doi.org/10.1007/s00394-016-1180-6

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  • DOI: https://doi.org/10.1007/s00394-016-1180-6

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