The probiotic Streptococcus salivarius M18 increases plasma nitrite but does not alter blood pressure: a pilot randomised controlled trial

Mia C. Burleigh*, Bob T. Rosier, Annabel Simpson, Nicholas Sculthorpe, Fiona Henriquez, Chris Easton

*Corresponding author for this work

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Some species of oral bacteria can reduce dietary nitrate to nitrite, which can later be converted to nitric oxide in the nitrate—nitrite—nitic oxide pathway. Increasing nitric oxide availability can reduce blood pressure (BP) and improve exercise performance. Streptococcus salivarius M18 (Streptococcus salivarius M18) is a bacteriocin-producing probiotic that is known to improve oral health by inhibiting pathogenic oral bacteria. However, it is presently unclear whether probiotic-induced alterations to the oral microbiome will influence circulating levels of nitric oxide metabolites and BP. Purpose: To determine the effects of Streptococcus salivarius M18 supplementation on plasma and salivary nitrate and nitrite levels and BP. Methods: Ten healthy males (age 32 ± 8 y, body mass 88.2 ± 15.1 kg) completed 2 × 14-day supplementation phases in a randomized order at least 14 days apart. In one phase, participants consumed Streptococcus salivarius M18 probiotic lozenges (2.5 billion colony-forming units/dose) once per day, and in the other, they ingested water (placebo). The abundance of bacteria on the tongue was assessed via Illumina 16S rRNA gene sequencing, unstimulated saliva, and venous blood samples were collected, and BP was measured pre and post each phase. Saliva and plasma were analysed for nitrate and nitrite using chemiluminescence, and pH was measured in saliva. The change in each outcome from pre- to post-supplementation was compared between phases using repeated measures ANOVA. Results: Plasma nitrite increased from baseline following probiotic supplementation (from 173 ± 39 to 223 ± 63 nM, p = 0.003, 95% CI 192–250 nM). In comparison, there was no change in the placebo phase or between baselines (all p > 0.05). The abundance of nitrite-producing bacteria was not altered, salivary nitric oxide metabolites and pH did not change, and the increase in plasma nitrite did not result in reductions in BP (all p > 0.05). Conclusions: Supplementation with Streptococcus salivarius M18 increased plasma nitrite, a key marker of NO availability. Despite this, Streptococcus salivarius M18 did not lower BP in these healthy normotensive participants. Additionally, the increase in plasma nitrite was not associated with abundance changes in bacteria thought important to NO generation. Further research is required to determine the mechanism behind the increase in plasma nitrite and the potential therapeutic and ergogenic benefits of Streptococcus salivarius M18 supplementation.
Original languageEnglish
Pages (from-to)774-785
Number of pages12
JournalApplied Microbiology
Issue number3
Publication statusPublished - 13 Jul 2023


  • nitric oxide 1
  • nitrate 2
  • nitrite 3
  • probiotic
  • Streptococcus salivarius M18
  • blood pressure
  • oral health
  • cardiovascular health


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