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Effects of Human Milk Oligosaccharides on Infants’ Gut Microbiota

Early intestinal microbiota development has become an important aspect of infants’ health.(1, 2) Initial microbial colonisation of the newborns’ gut is a vital component in the development of the gastrointestinal tract, particularly maturation of the gut barrier function and intestinal immune system.(1, 3-6) Although some immune defences of infants have developed during pregnancy, actual active immune protection occurs only when adequate colonising bacteria stimulate the gut mucosal wall.(3, 5)

Maternal microbiota seems to form the first microbial inoculum, and after birth, the microbial diversity increases and converges towards an adult-like microbiota by the end of 3 to 5 years of life.(1) Various factors are known to influence microbial colonisation during early life, such as mode of delivery, use of antibiotics and type of infant feeding.(1, 3, 7) Early-life imbalances of normal gut microbial colonisation, also called dysbiosis, are associated with an increased risk of certain diseases.(1-3)


Breast milk plays an important role in the development of mature immune responses in babies during early life.(6) Gut microbiota development of breastfed infants is characterized by an early colonization of beneficial gut microbiota, such as bifidobacteria.(1, 6) Evidence further suggests that breastfed infants also have a high abundance of these beneficial gut bacteria in comparison with infants receiving a typical infant formula.(1, 6) Breast milk is known to provide a number of bioactive components, including human milk oligosaccharides (HMOs), which support the development of a normal protective gut microbiota.(6, 8, 9) HMOs, which are the third largest solid components in breast milk, serve as food for the selective growth and metabolic activity of certain beneficial gut bacteria and provide them with a growth advantage over potential pathogens.(9-12)


A first clinical, intervention trial testing an infant formula supplemented with 2 HMOs, 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT), showed promising effects of these 2 HMOs on early gut microbiota development.(13, 14)


Infants fed the formula with the 2 HMOs developed gut microbiota closer to that of breastfed infants, in comparison to infants fed the formula without these HMOs.(13, 14) At 3 months of age, the infants’ stool microbiota was characterized by an increased quantity of beneficial bifidobacteria and decreased abundances of taxa with potentially pathogenic members.(13, 14) Moreover, the supplementation of infant formula with these 2 HMOs promoted the growth of a distinct faecal bacterial community that is typical of breastfed infants and showing a very high bacterial density.(13) Interestingly, this shift in stool microbiota seems to be associated with less use of antibiotics during the first year of life.(13)


Professor Clemens Kunz, University Giessen, Germany


Bifidobacteria are significant beneficial colonizers in the newborns’ gut. Hence, their stimulation of growth by HMOs added to infant formulae is important within the concept of disease prevention. Not all Bifidobacteria, but only certain subspecies and strains, are able to utilize HMOs. Upcoming studies in infants will provide answers to the questions: (i) which bifidobacterial strains and subspecies will be stimulated by which HMO (ii) how various microorganisms in the infant gut, i.e. Bifidobacteria, Lactobacilli and others, do communicate with each other and improve the growth of one another.


A possible mechanism for this interaction is a process called cross-feeding. Whereby, bacterial metabolites such as acetate, propionate or lactate, which are produced by certain microorganisms but not others, can ‘feed’ other microorganisms that only use but do not produce them. It will be intriguing to see which health effects will result from the interactions within the microbiota initiated by the addition of HMOs to infant formulae.



References


1.Rodriguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.

2.Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014;5:427.

3.Walker A. Intestinal colonization and programming of the intestinal immune response. J Clin Gastroenterol. 2014;48 Suppl 1:S8-11.

4.Walker WA. Development of the intestinal mucosal barrier. J Pediatr Gastroenterol Nutr. 2002;34 Suppl 1:S33-9.

5.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.

6.Collado MC, Cernada M, Bauerl C, Vento M, Perez-Martinez G. Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes. 2012;3(4):352-65.

7.Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015;17(5):690-703.

8.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.

9.Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62.

10.Sela DA, Mills DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol. 2010;18(7):298-307.

11.Yu ZT, Chen C, Newburg DS. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology. 2013;23(11):1281-92.

12.Morozov V, Hansman G, Hanisch FG, Schroten H, Kunz C. Human Milk Oligosaccharides as Promising Antivirals. Mol Nutr Food Res. 2018;62(6):e1700679.

13.Berger B, Sprenger N, Grathwohl D, Alliet P, Puccio G, Steenhout P. Stool microbiota in term infants fed formula supplemented with synthetic human milk oligosaccharides is associated with reduced likelihood of medication. J Pediatr Gastroenterol Nutr 2016;62(Suppl 2):S406.

14.Steenhout P, Sperisen P, Martin F-P, Sprenger N, Wernimont S, Pecquet S, et al. Term infant formula supplemented with human milk oligosaccharides (2′Fucosyllactose and Lacto-­N-neotetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. The FASEB Journal. 2016;30(1 Suppl):257.7.

 

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