Breastmilk-saliva interactions boost innate immunity by regulating the oral microbiome in early infancy

Al-Shehri, Saad S., Knox, Christine L., Liley, Helen G., Cowley, David M., Wright, John R., Henman, Michael G., Hewavitharana, Amitha K., Charles, Bruce G., Shaw, Paul N., Sweeney, Emma L., & Duley, John A. (2015) Breastmilk-saliva interactions boost innate immunity by regulating the oral microbiome in early infancy. PLoS ONE, 10(9), e0135047.

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Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined.


Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3±12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2–449) compared to adults (620 U/L, 48–1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns.

Discussion and Conclusion

During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.

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ID Code: 90827
Item Type: Journal Article
Refereed: Yes
Keywords: Nucleosides, Nucleobases, Neonatal immunity, Saliva, Xanthine oxidase, Reactive oxygen species, Microbiota
DOI: 10.1371/journal.pone.0135047
ISSN: 1932-6203
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 Al-Shehri et al
Copyright Statement: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Deposited On: 27 Nov 2015 02:57
Last Modified: 29 Nov 2015 22:34

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