Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria
Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria
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DOI：
10.1016/j.freeradbiomed.2018.03.023
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发表时间：
2018-05-20
影响因子：
7.4
通讯作者：
Easton, Chris
中科院分区：
文献类型：
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作者：
Burleigh, Mia C.;Liddle, Luke;Easton, Chris
一氧化氮（NO）可以通过NO还原酶内源性地产生，或者在口腔中共生的硝酸盐还原菌的作用下通过饮食产生。鉴于NO在平滑肌控制中的重要作用，有一个有趣的建议，即心血管稳态可能与这些细菌的存在交织在一起。在这里，我们使用16S rRNA测序测量了25名健康人口腔中硝酸盐还原菌的丰度，并观察了3.5小时，通过测量血压，唾液和血浆NO代谢产物对饮食硝酸盐摄入的生理反应。我们确定了7种以前已知的有助于硝酸盐还原的细菌，其中最普遍的是产黑色素普雷沃氏菌和韦荣氏菌。在饮食中补充硝酸盐后，血压降低，唾液和血浆硝酸盐和亚硝酸盐大幅增加。我们发现硝酸盐还原菌的丰度与唾液亚硝酸盐的产生有关，但与任何其他测量变量无关。为了研究细菌丰度对药代动力学的影响，我们还将参与者分为两组：硝酸盐还原菌丰度较高的组（> 50%）和丰度较低的组（< 50%）。唾液亚硝酸盐的产生在细菌丰度较低的参与者中较低，这些个体也表现出较慢的唾液亚硝酸盐药代动力学。因此，我们表明，在口腔中的硝酸盐还原为亚硝酸盐的速率与硝酸盐还原菌的丰度有关。然而，这些细菌的丰度较高并不会导致夸大的血浆亚硝酸盐反应，这是NO生物利用度的最佳标志物。来自健康年轻人的这些数据表明，口腔硝酸盐还原菌的丰度不会影响通过饮食产生NO，至少当宿主具有这些微生物的功能最低阈值时。
Nitric oxide (NO) can be generated endogenously via NO synthases or via the diet following the action of symbiotic nitrate-reducing bacteria in the oral cavity. Given the important role of NO in smooth muscle control there is an intriguing suggestion that cardiovascular homeostasis may be intertwined with the presence of these bacteria. Here, we measured the abundance of nitrate-reducing bacteria in the oral cavity of 25 healthy humans using 16S rRNA sequencing and observed, for 3.5 h, the physiological responses to dietary nitrate ingestion via measurement of blood pressure, and salivary and plasma NO metabolites. We identified 7 species of bacteria previously known to contribute to nitrate-reduction, the most prevalent of which were Prevotella melaninogenica and Veillonella dispar. Following dietary nitrate supplementation, blood pressure was reduced and salivary and plasma nitrate and nitrite increased substantially. We found that the abundance of nitrate-reducing bacteria was associated with the generation of salivary nitrite but not with any other measured variable. To examine the impact of bacterial abundance on pharmacokinetics we also categorised our participants into two groups; those with a higher abundance of nitrate reducing bacteria (> 50%), and those with a lower abundance (< 50%). Salivary nitrite production was lower in participants with lower abundance of bacteria and these individuals also exhibited slower salivary nitrite pharmacokinetics. We therefore show that the rate of nitrate to nitrite reduction in the oral cavity is associated with the abundance of nitrate-reducing bacteria. Nevertheless, higher abundance of these bacteria did not result in an exaggerated plasma nitrite response, the best known marker of NO bioavailability. These data from healthy young adults suggest that the abundance of oral nitrate-reducing bacteria does not influence the generation of NO through the diet, at least when the host has a functional minimum threshold of these microorganisms.