Breastmilk-Saliva Interactions Boost Innate Immunity by Regulating the Oral Microbiome in Early Infancy.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
School of Pharmacy, The University of Queensland, Brisbane, Australia; College of Applied Medical Science, Taif University, Taif, Saudi Arabia.
Saad S
SS
Al-Shehri
Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
Christine L
CL
Knox
Mater Research Institute, Mater Health Services, Brisbane, Australia.
Helen G
HG
Liley
Mater Research Institute, Mater Health Services, Brisbane, Australia.
David M
DM
Cowley
School of Veterinary Science, The University of Queensland, Gatton, Australia.
John R
JR
Wright
Mater Research Institute, Mater Health Services, Brisbane, Australia.
Michael G
MG
Henman
School of Pharmacy, The University of Queensland, Brisbane, Australia.
Amitha K
AK
Hewavitharana
School of Pharmacy, The University of Queensland, Brisbane, Australia.
Bruce G
BG
Charles
School of Pharmacy, The University of Queensland, Brisbane, Australia.
Paul N
PN
Shaw
Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
Emma L
EL
Sweeney
School of Pharmacy, The University of Queensland, Brisbane, Australia; Mater Research Institute, Mater Health Services, Brisbane, Australia.
John A
JA
Duley
D000328:Adult; D005260:Female; D007231:Infant, Newborn; D008297:Male; D006861:Hydrogen Peroxide / Q000032:analysis; D019271:Hypoxanthine / Q000032:analysis; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology; D064307:Microbiota / Q000276:immunology; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D009055:Mouth / Q000276:immunology / Q000382:microbiology; D009711:Nucleotides / Q000032:analysis / Q000378:metabolism; D012463:Saliva / Q000737:chemistry / Q000276:immunology; D013861:Thiocyanates / Q000032:analysis; D019820:Xanthine / Q000032:analysis; D014969:Xanthine Oxidase / Q000032:analysis; D006801:Humans
D006861:Hydrogen Peroxide; D019271:Hypoxanthine; D009711:Nucleotides; C031760:thiocyanate; D013861:Thiocyanates; D019820:Xanthine; D014969:Xanthine Oxidase