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Human Milk Oligosaccharides offer Protection against gastrointestinal and respiratory Infections

During early life, babies are typically susceptible to infections, especially gastrointestinal and respiratory infections, which is largely related to their immature immune system.1,2
Breast milk is the nature’s most perfect source of babies’ nutrition and has many beneficial effects.3 Apart from providing adequate nutrients for babies’ healthy growth and development, breast milk offers various health benefits, such as protection against infectious gastrointestinal and respiratory diseases.4-7 Among the many different elements of breast milk, human milk oligosaccharides (HMOs) are the third most common solid component.8,9 They provide unique benefits to babies, including protection against infections.9-12

HMOs can directly act as decoy receptors or act on epithelial cells, thus preventing pathogen attachment on epithelial cells.9,10,13 This unique beneficial effect of HMOs is highly dependent on their structure,14,15 and has been shown for fucosylated HMOs and 2′-fucosyllactose (2′FL) in protecting against Campylobacter jejuni in experimental and preclinical studies, respectively.16,17 C. jejuni is one of the major causes of bacterial diarrhoea, worldwide.16 Another mechanism through which HMOs can protect against pathogens is indirectly through the modulation of the gut microbiota, including the stimulation of beneficial bifidobacteria.9,15

The first promising evidence from observational, clinical studies provide support that 2′-fucosylated HMOs have a protective effect on gastrointestinal and respiratory infections.18-20 In breastfed infants, Campylobacter-induced diarrhoea occurred less often in those infants receiving breast milk with higher levels of 2′-fucosylated HMOs, such as 2′FL than in those infants who received breast milk with lower levels of these HMOs.18 Furthermore, moderate to severe diarrhoea of all causes was less frequent in infants receiving breast milk with higher levels of 2′-fucosylated HMOs; this protective effect was dose-dependent.18 In another community-based, longitudinal cohort study, breastfed infants of secretor mothers with typically higher levels of 2′-fucosylated HMOs had a reduced risk of acute respiratory infections during the period of predominant breastfeeding.19 Similarly, 2′-fucosylated HMOs in breast milk were related to fewer respiratory and enteric problems in a further observational study of breastfed infants at 3 months of age.20


Professor Hania Szajewska, Department of Paediatrics of The Medical University of Warsaw, Poland



The health benefits of breastfeeding, particularly protection against childhood infections, may be, at least partially, related to the presence of HMOs. The data summarised above assessed the relationship between concentrations of 2′-fucosylated HMOs in mothers’ milk, which are the most abundant HMOs in the milk of secretor mothers, and the subsequent development of infectious diseases in breastfed infants.
These data from observational studies may be biased by possible confounding factors, such as the presence of siblings, passive smoke exposure or season of birth. Thus, observational studies provide evidence of an association only, which is not the same as causation.
Still, the interest in the effects of HMOs is increasing in line with progress in biotechnology, which nowadays allows the production of at least some HMOs (mainly, albeit not exclusively, 2′FL and lacto-N-neotetraose [LNnT]) to be added to infant formulae. Documenting the beneficial effects of specific HMOs present in breast milk supports the concept that the addition of the same HMOs to infant formula may potentially reduce the burden of infections in infants. Future, randomised, controlled trials should investigate such health benefits of adding HMOs to infant formulae.


References

1.World Health Organisation W. WHO recommendations on the management of diarrhoea and pneumonia in HIV-infected infants and children: integrated management of childhood illness (IMCI). Geneva, Switzerland2010. https://apps.who.int/iris/bitstream/handle/10665/44471/9789241548083_eng.pdf?sequence=1&isAllowed=y
2.Martin R, Nauta AJ, Ben Amor K, Knippels LM, Knol J, Garssen J. Early life: gut microbiota and immune development in infancy. Benef Microbes. 2010;1(4):367-82. https://www.wageningenacademic.com/doi/pdf/10.3920/BM2010.0027
3.Agostoni C, Braegger C, Decsi T, et al. Breast-feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2009;49(1):112-25. https://journals.lww.com/jpgn/fulltext/2009/07000/Breast_feeding__
A_Commentary_by_the_ESPGHAN.18.aspx#pdf-link

4.Horta BL, Victora CG. Short-term effects of breastfeeding: a systematic review on the benefits of breastfeeding on diarrhoea and pneumonia mortality. 2013; https://apps.who.int/iris/bitstream/handle/10665/95585/9789241506120_eng.pdf; jsessionid=126665DF3E351CFC9AA740FED9820757?sequence=1. cited July 29, 2019.
5.Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: a meta-analysis. Arch Pediatr Adolesc Med. 2003;157(3):237-43. https://jamanetwork.com/journals/jamapediatrics/fullarticle/481276
6.Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012(8):CD003517. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003517.pub2/full
7.Duijts L, Jaddoe VW, Hofman A, Moll HA. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics. 2010;126(1):e18-25. https://pediatrics.aappublications.org/content/126/1/e18.long  
8.Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci USA. 2011;108 (Suppl 1):4653-8. https://www.pnas.org/content/pnas/108/Supplement_1/4653.full.pdf
9.Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62. https://academic.oup.com/glycob/article/22/9/1147/1988076
10.Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000;20:699-722. https://www.ncbi.nlm.nih.gov/pubmed/10940350
11.Rudloff S, Kunz C. Milk oligosaccharides and metabolism in infants. Adv Nutr. 2012;3(3):398S-405S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649476/pdf/398S.pdf
12.Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013;60(1):49-74. https://www.sciencedirect.com/science/article/pii/S0031395512001678?via%3Dihub
13.Morozov V, Hansman G, Hanisch FG, Schroten H, Kunz C. Human milk oligosaccharides as promising antivirals. Mol Nutr Food Res. 2018;62(6):e1700679. https://www.ncbi.nlm.nih.gov/pubmed/29336526
14.Bode L, Jantscher-Krenn E. Structure-function relationships of human milk oligosaccharides. Adv Nutr. 2012;3(3):383S-91S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649474/pdf/383S.pdf
15.Vandenplas Y, Berger B, Carnielli VP, et al. Human milk oligosaccharides: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) in infant formula. Nutrients. 2018;10(9):1161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164445/pdf/nutrients-10-01161.pdf
16.Ruiz-Palacios GM, Cervantes LE, Ramos P, Chavez-Munguia B, Newburg DS. Campylobacter jejuni binds intestinal H(O) antigen (Fuc alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J Biol Chem. 2003;278(16):14112-20. http://www.jbc.org/content/278/16/14112.full.pdf
17.Yu ZT, Nanthakumar NN, Newburg DS. The Human Milk Oligosaccharide 2'-Fucosyllactose Quenches Campylobacter jejuni-Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa. J Nutr. 2016;146(10):1980-90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037868/pdf/jn230706.pdf
18.Morrow AL, Ruiz-Palacios GM, Altaye M, et al. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr. 2004;145(3):297-303. https://reader.elsevier.com/reader/sd/pii/S0022347604003750?token=0AACDB2B2EC9631AF824823CB38D929F3AF8B8FE5DA9B329899480B3C8A2112981362 EC92F31DAC83819F9F91CDD2112
19.Binia A, Sprenger N, Lefebvre G, et al. Maternal secretor status is associated with reduced incidence of respiratory infections in infants in the microbiota and health cohort J Pediatr Gastroenterol Nutr. 2019;68(Suppl 1):992.
20.Stepans MB, Wilhelm SL, Hertzog M, et al. Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants. Breastfeed Med. 2006;1(4):207-15. https://www.ncbi.nlm.nih.gov/pubmed/?term=Early+consumption+of+human+milk+oligosaccharides+is+inversely+related+to+subsequent+risk +of+respiratory+and+enteric+disease+in+infants
 

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