Investigating the association between nitrate dosing and nitrite generation by the human oral microbiota in continuous culture.

The generation of nitrite by the oral microbiota is believed to contribute to healthy cardiovascular function, with oral nitrate reduction to nitrite associated with systemic blood pressure regulation. There is the potential to manipulate the composition or activities of the oral microbiota to a higher nitrate-reducing state through nitrate supplementation. The current study examined microbial community composition and enzymatic responses to nitrate supplementation in sessile oral microbiota grown in continuous culture. Nitrate reductase (NaR) activity and nitrite concentrations were not significantly different to tongue-derived inocula in model biofilms. These were generally dominated by Streptococcus spp., initially, and a single nitrate supplementation resulted in the increased relative abundance of the nitrate-reducing genera Veillonella, Neisseria, and Proteus spp. Nitrite concentrations increased concomitantly and continued to increase throughout oral microbiota development. Continuous nitrate supplementation, over a 7-day period, was similarly associated with an elevated abundance of nitrate-reducing taxa and increased nitrite concentration in the perfusate. In experiments in which the models were established in continuous low or high nitrate environments, there was an initial elevation in nitrate reductase, and nitrite concentrations reached a relatively constant concentration over time similar to the acute nitrate challenge with a similar expansion of Veillonella and Neisseria. In summary, we have investigated nitrate metabolism in continuous culture oral biofilms, showing that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of putatively NaR-producing taxa.IMPORTANCEClinical evidence suggests that blood pressure regulation can be promoted by nitrite generated through the reduction of supplemental dietary nitrate by the oral microbiota. We have utilized oral microbiota models to investigate the mechanisms responsible, demonstrating that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of nitrate-reducing taxa.

Antibacterial effects in blood irradiated with a polychromatic device mediated through reactive oxygen species: possible involvement of haem.

The antibacterial effects of a polychromatic light device designed for intravenous application were assessed in vitro. Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli were exposed to a 60-min sequential light cycle comprising 365, 530, and 630 nm wavelengths in circulated sheep blood. Bacteria were quantified by viable counting. The potential involvement of reactive oxygen species in the antibacterial effect was assessed using the antioxidant N-acetylcysteine-amide. A modified device was then used to determine the effects of the individual wavelengths. Exposure of blood to the standard wavelength sequence caused small (c. 0.5 Log 10 CFU) but statistically significant reductions in viable counts for all three bacteria, which were prevented by the addition of N-acetylcysteine-amide. Bacterial inactivation did not occur in blood-free medium, but supplementation with haem restored the moderate bactericidal effect. In single-wavelength experiments, bacterial inactivation occurred only with red (630 nm) light. Concentrations of reactive oxygen species were significantly higher under light stimulation than in unstimulated controls. In summary, exposure of bacteria within blood to a cycle of visible light wavelengths resulted in small but statistically significant bacterial inactivation apparently mediated by a 630 nm wavelength only, via reactive oxygen species possibly generated by excitation of haem groups.

RISING STARS: Bumps and bacteria: influence of the maternal microbiota on pregnancy outcomes.

During pregnancy, all major physiological systems undergo remarkable changes, driven largely by alterations in the maternal hormonal milieu. In healthy pregnancies, maternal cardiovascular and metabolic adaptation to pregnancy occurs to support fetal growth and maternal well-being. Impaired maternal adaptation to pregnancy is associated with a range of pregnancy complications, including gestational diabetes and preeclampsia. There is growing recognition of the importance of different maternal microbiota, including in the gut, vagina and oral cavity, in supporting normal maternal adaptations to pregnancy as well as evidence for microbial disturbances associating with pregnancy pathologies. Here, we aim to summarise emerging evidence demonstrating that differences in maternal microbiota associate with pregnancy outcomes and discuss potential therapeutic approaches under development that might restore an 'optimal' microbiome. In particular, we highlight recent work by ourselves and others exploring the role of the oral microbiome in pregnancy, given established links between poor oral health (e.g. periodontitis) and adverse pregnancy outcomes. Our research has focussed on specific nitrate-reducing oral bacteria which play a role in the generation of nitric oxide (NO) and other bioactive nitrogen oxides associated with cardiovascular health and maternal cardiovascular adaption to pregnancy. Ongoing research aims to define whether altered microbial profiles have clinical utility in the prediction of pregnancy pathologies, and whether interventions designed to optimise specific maternal microbiota could help prevent future complications.

Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity.

Introduction: The skin microbiota plays a crucial role in maintaining epidermal homeostasis. Ultraviolet radiation (UVR) and other environmental challenges can impact the skin microbiota through direct and indirect mechanisms. This study aimed to investigate the effects of sun exposure on the skin microbiota and its relationship with individual skin phototypes. Methods: Healthy volunteers (n = 21 [4M, 17 F], mean age 33.2 years) holidayed in a sunny destination for a minimum of 7 days with swabs taken pre-holiday and up to 84 days post-holiday. Participant group was categorised by individual typology angle (ITA) classification and the composition of the skin microbiota was examined using 16S rRNA gene sequencing. Results: In the entire cohort and at all time points, the major bacterial phyla were Actinobacteria, Proteobacteria and Firmicutes. There was a significant change in microbial beta diversity at day 28 post-holiday, compared to baseline, for all participants. However, when participants were segregated into three cohorts dependent on the degree of skin tanning response between baseline (pre-holiday) and immediately one-day post-holiday, there was a reduction in Proteobacteria in the sun-seeking participants 1 day after the holiday, which recovered over time. Discussion: These findings suggest that sun exposure can affect the diversity and composition of the skin microbiota, which may have downstream effects on skin health.

Altered Oral Nitrate Reduction and Bacterial Profiles in Hypertensive Women Predict Blood Pressure Lowering Following Acute Dietary Nitrate Supplementation.

BACKGROUND: The efficacy of dietary nitrate supplementation to lower blood pressure (BP) in pregnant women is highly variable. We aimed to investigate whether differences in oral microbiota profiles and oral nitrate-reducing capacity may explain interindividual differences in BP lowering following nitrate supplementation. METHODS: Participants recruited for this study were both pregnant and nonpregnant women, with or without hypertension (n=55). Following an overnight fast, plasma, saliva, and tongue scraping samples were collected for measurement of nitrate/nitrite concentrations, oral NaR (nitrate reductase) activity, and microbiota profiling using 16S rRNA gene sequencing. Baseline BP was measured, followed by the administration of a single dose of dietary nitrate (400 mg nitrate in 70 mL beetroot juice). Post-nitrate intervention, plasma and salivary nitrate/nitrite concentrations and BP were determined 2.5 hours later. RESULTS: Women with hypertension had significantly lower salivary nitrite concentrations (P=0.006) and reduced abundance of the nitrate-reducing taxa Veillonella(P=0.007) compared with normotensive women. Oral NaR activity was not significantly different in pregnant versus nonpregnant women (P=0.991) but tended to be lower in hypertensive compared with normotensive women (P=0.099). Oral NaR activity was associated with both baseline diastolic BP (P=0.050) and change in diastolic BP following acute nitrate intake (P=0.01, adjusted for baseline BP). CONCLUSIONS: The abundance and activity of oral nitrate-reducing bacteria impact both baseline BP as well as the ability of dietary nitrate supplementation to lower BP. Strategies to increase oral nitrate-reducing capacity could lower BP and enhance the efficacy of dietary nitrate supplementation, in pregnancy as well as in nonpregnant adults. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03930693.

Does the Oral Microbiome Play a Role in Hypertensive Pregnancies?

Chronic hypertension during gestation is associated with an increased risk of adverse pregnancy outcomes including pre-eclampsia, fetal growth restriction and preterm birth. Research into new chemotherapeutic regimes for the treatment of hypertension in pregnancy is limited due to concerns about fetal toxicity and teratogenicity, and new therapeutic avenues are being sought in alternative physiological pathways. Historically, generation of the vasodilator nitric oxide was believed to be solely from L-arginine by means of nitric oxide synthase enzymes. Recently, a novel pathway for the reduction of dietary inorganic nitrate to nitrite by the bacteria in the oral cavity and subsequently to vasodilatory nitric oxide within the body has been uncovered. Dietary nitrate is abundant in green leafy vegetables, including beetroot and spinach, and reduction of exogenous nitrate to nitrite by oral bacteria can increase nitric oxide in the vasculature, lessening hypertension. Supplements rich in nitrate may be an attractive choice for treatment due to fewer side effects than drugs that are currently used to treat hypertensive pregnancy disorders. Additionally, manipulation of the composition of the oral microbiota using pro- and prebiotics in tandem with additional dietary interventions to promote cardiovascular health during gestation may offer a safe and effective means of treating hypertensive pregnancy disorders including gestational hypertension and pre-eclampsia. The use of dietary inorganic nitrate as a supplement during pregnancy requires further exploration and large scale studies before it may be considered as part of a treatment regime. The aim of this article is to review the current evidence that oral microbiota plays a role in hypertensive pregnancies and whether it could be manipulated to improve patient outcomes.