Nitrate reductase activity of bacteria in saliva of term and preterm infants

Abstract

The salivary glands of adults concentrate nitrate from the plasma into saliva where it is converted to nitrite by bacterial nitrate reductases. Nitrite can play a beneficial role in adult gastrointestinal and cardiovascular physiology. When nitrite is swallowed, some of it is converted to nitric oxide (NO) in the stomach and may then exert protective effects in the gastrointestinal tract and throughout the body. It has yet to be determined either when newborn infants acquire oral nitrate reducing bacteria or what the effects of antimicrobial therapy or premature birth may be on the bacterial processing of nitrate to nitrite. We measured nitrate and nitrite levels in the saliva of adults and both preterm and term human infants in the early weeks of life. We also measured oral bacterial reductase activity in the saliva of both infants and adults, and characterized the species of nitrate reducing bacteria present. Oral bacterial conversion of nitrate to nitrite in infants was either undetectable or markedly lower than the conversion rates of adults. No measurable reductase activity was found in infants within the first two weeks of life, despite the presence of oral nitrate reducing bacteria such as Actinomyces odontolyticus, and Veillonella atypica, and Rothia mucilaginosa. We conclude that relatively little nitrite reaches the infant gastrointestinal tract due to the lack of oral bacterial nitrate reductase activity. Given the importance of the nitrate-nitrite-NO axis in adults, the lack of oral nitrate-reducing bacteria in infants may be relevant to the vulnerability of newborns to hypoxic stress and gastrointestinal tract pathologies.

Dietary intake and bio-activation of nitrite and nitrate in newborn infants

“…The transport of nitrate has been suggested to be mediated by the enzyme sialin via an adenosine 59-triphosphate-dependent electrogenic NO 3 − /H + transport mechanism in the salivary acinar cells (25). The nitrate concentration in the saliva of newborns is approximately 200 μmol/l, similar to that of adults (26). As in adults, this concentration is many-fold higher than in blood (16–40 μmol/l).…”

“…Veillonella and Actinomyces species have been found in saliva collected from infants in the first 2 mo of life and appear to be some of the first bacteria to colonize the mouths of newborns (26,31–33). Despite the presence of these bacteria, oral nitrate reductase activity is markedly lower in newborn infants when compared with adults, as shown in Figure 3.…”

“…While there is measurable nitrate-reducing capacity in swabs (normalized to the saliva content in the swab) collected from infants at 2–8wk of age, the rate of nitrite production is only ~10% of that of adults (26), as illustrated in Figure 3. Notably, infants also produce relatively small volumes of saliva during the first few weeks of life, which may attenuate bacterial growth and may also result in less swallowed salivary nitrite compared with the adult (26). The developmental time point at which the nitrate-reducing capacity of the infant mouth becomes comparable to the adult is unknown.…”

“…Another potential cause of relatively low plasma nitrite in infants could be the lack of significant oral bacterial nitrate reduction, as discussed above and illustrated in Figure 3. We have recently shown that adults given antibacterial mouth rinse have significantly reduced plasma nitrite concentrations (26), highlighting the importance of the oral nitrate-reducing bacteria to the amount of circulating nitrite. Thus, with the confluence of all of these factors, it appears that nitrite bioavailability is diminished in the newborn by a system of concerted mechanisms, as evidenced by the sharp fall in nitrite concentrations at birth.…”

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract

“…The methanogens (Methanobrevibacter smithii, Methanobrevibacter oralis, and Methanosphaera stadtmanae), the only archaea identified in humans, appear to aid in the development of bacteria that play direct roles in pathogenesis. Members of this domain can colonize the intestine, oral cavity, and skin (Kanady et al 2012). Archaea may affect oral health through interspecies hydrogen transfer and by favoring the growth of fermenting bacteria.…”