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

Al-Shehri SS, Knox CL, Liley HG, Cowley DM, Wright JR, Henman MG, Hewavitharana AK, Charles BG, Shaw PN, Sweeney EL, Duley JA - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, The University of Queensland, Brisbane, Australia; College of Applied Medical Science, Taif University, Taif, Saudi Arabia.

ABSTRACT

Introduction: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Concentration of nucleotide precursors in whole saliva samples of human adults, term neonates, and domesticated mammals.(A) Healthy non-smoking adults (n = 77) and (B) healthy full-term vaginally-delivered neonates (n = 60), lines show median values. Non-parametric analyses were conducted to estimate the significance using a Mann-Whitney U test, (C) Longitudinal study of median concentrations of metabolites in saliva from full-term neonates aged 1–4 days (n = 60), 6 weeks (n = 20), 6 months (n = 19), and 12 months (n = 14), (D) Median metabolite concentrations in saliva from selected domesticated mammals (8 cows, 5 sheep, 4 goats, 5 horses, 1 camel, 7 dogs, 5 cats). Metabolites were divided into five functional groups: Pyrimidines (Pseudouridine to Orotate); Purine bases (Hypoxanthine, Xanthine); Purine nucleosides (Inosine, Guanosine); ATP precursors (Adenine, Adenosine); Deoxynucleosides (Deoxyadenosine to Deoxyuridine).
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pone.0135047.g001: Concentration of nucleotide precursors in whole saliva samples of human adults, term neonates, and domesticated mammals.(A) Healthy non-smoking adults (n = 77) and (B) healthy full-term vaginally-delivered neonates (n = 60), lines show median values. Non-parametric analyses were conducted to estimate the significance using a Mann-Whitney U test, (C) Longitudinal study of median concentrations of metabolites in saliva from full-term neonates aged 1–4 days (n = 60), 6 weeks (n = 20), 6 months (n = 19), and 12 months (n = 14), (D) Median metabolite concentrations in saliva from selected domesticated mammals (8 cows, 5 sheep, 4 goats, 5 horses, 1 camel, 7 dogs, 5 cats). Metabolites were divided into five functional groups: Pyrimidines (Pseudouridine to Orotate); Purine bases (Hypoxanthine, Xanthine); Purine nucleosides (Inosine, Guanosine); ATP precursors (Adenine, Adenosine); Deoxynucleosides (Deoxyadenosine to Deoxyuridine).

Mentions: Among 77 adults that we screened, we found low or undetectable concentrations of nucleotide metabolites (excluding urate) except in 9 adults (Fig 1A). One adult had an anomalously high inosine, while eight subjects had mildly raised xanthine/hypoxanthine (the substrates of XO). The demographic parameters of 60 neonates are shown in Table 1. Among the neonates, median concentrations of salivary hypoxanthine and xanthine were ten-fold higher (27 μM and 19 μM respectively) than median adult values (2.1 and 1.7 μM respectively) (p <0.05) (Fig 1B). Interestingly, while some nucleosides and bases were raised in the neonates, others such as pseudouridine, thymine and dihydrothymine were always low, while deoxy-nucleosides were undetectable. The pyrimidine base orotic acid was interesting: although the median concentrations were less than 1 μM for most adults and neonates, several neonatal saliva samples exceeded 10 μM orotic acid.


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

Al-Shehri SS, Knox CL, Liley HG, Cowley DM, Wright JR, Henman MG, Hewavitharana AK, Charles BG, Shaw PN, Sweeney EL, Duley JA - PLoS ONE (2015)

Concentration of nucleotide precursors in whole saliva samples of human adults, term neonates, and domesticated mammals.(A) Healthy non-smoking adults (n = 77) and (B) healthy full-term vaginally-delivered neonates (n = 60), lines show median values. Non-parametric analyses were conducted to estimate the significance using a Mann-Whitney U test, (C) Longitudinal study of median concentrations of metabolites in saliva from full-term neonates aged 1–4 days (n = 60), 6 weeks (n = 20), 6 months (n = 19), and 12 months (n = 14), (D) Median metabolite concentrations in saliva from selected domesticated mammals (8 cows, 5 sheep, 4 goats, 5 horses, 1 camel, 7 dogs, 5 cats). Metabolites were divided into five functional groups: Pyrimidines (Pseudouridine to Orotate); Purine bases (Hypoxanthine, Xanthine); Purine nucleosides (Inosine, Guanosine); ATP precursors (Adenine, Adenosine); Deoxynucleosides (Deoxyadenosine to Deoxyuridine).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556682&req=5

pone.0135047.g001: Concentration of nucleotide precursors in whole saliva samples of human adults, term neonates, and domesticated mammals.(A) Healthy non-smoking adults (n = 77) and (B) healthy full-term vaginally-delivered neonates (n = 60), lines show median values. Non-parametric analyses were conducted to estimate the significance using a Mann-Whitney U test, (C) Longitudinal study of median concentrations of metabolites in saliva from full-term neonates aged 1–4 days (n = 60), 6 weeks (n = 20), 6 months (n = 19), and 12 months (n = 14), (D) Median metabolite concentrations in saliva from selected domesticated mammals (8 cows, 5 sheep, 4 goats, 5 horses, 1 camel, 7 dogs, 5 cats). Metabolites were divided into five functional groups: Pyrimidines (Pseudouridine to Orotate); Purine bases (Hypoxanthine, Xanthine); Purine nucleosides (Inosine, Guanosine); ATP precursors (Adenine, Adenosine); Deoxynucleosides (Deoxyadenosine to Deoxyuridine).
Mentions: Among 77 adults that we screened, we found low or undetectable concentrations of nucleotide metabolites (excluding urate) except in 9 adults (Fig 1A). One adult had an anomalously high inosine, while eight subjects had mildly raised xanthine/hypoxanthine (the substrates of XO). The demographic parameters of 60 neonates are shown in Table 1. Among the neonates, median concentrations of salivary hypoxanthine and xanthine were ten-fold higher (27 μM and 19 μM respectively) than median adult values (2.1 and 1.7 μM respectively) (p <0.05) (Fig 1B). Interestingly, while some nucleosides and bases were raised in the neonates, others such as pseudouridine, thymine and dihydrothymine were always low, while deoxy-nucleosides were undetectable. The pyrimidine base orotic acid was interesting: although the median concentrations were less than 1 μM for most adults and neonates, several neonatal saliva samples exceeded 10 μM orotic acid.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, The University of Queensland, Brisbane, Australia; College of Applied Medical Science, Taif University, Taif, Saudi Arabia.

ABSTRACT

Introduction: 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.

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.

No MeSH data available.


Related in: MedlinePlus