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The mouth–nitric oxide connection

Part of your nitric oxide pathway starts in your mouth.

Certain oral bacteria convert dietary nitrate into nitrite, an early step in the body's enterosalivary nitrate pathway.

Nitric oxide is a signalling molecule involved in vascular tone and blood-flow biology. Your body makes it two ways. One uses an enzyme family called nitric oxide synthase. The other starts with dietary nitrate from leafy greens and beets, and it depends on bacteria. Nitrate is absorbed, concentrated by the salivary glands and returned to the mouth, where certain oral bacteria reduce it to nitrite. Human cells do not perform that first conversion efficiently on their own. Swallowed nitrite is then converted downstream. Only some oral bacteria carry the machinery for that step, which is why the capacity can be measured — as a gene rather than inferred from which species happen to be present.

What nitric oxide does

Nitric oxide is a small signalling molecule. In vascular biology it is involved in the relaxation of smooth muscle in vessel walls, which is part of how vascular tone and blood flow are regulated. It also has roles in immune signalling and in how tissue responds to injury.

It is produced throughout the body, continuously, and has a very short life once made.

Two ways your body makes it

The first uses a family of enzymes called nitric oxide synthase, which produce nitric oxide from the amino acid arginine. This pathway needs oxygen.

The second runs the other direction, from nitrate to nitrite to nitric oxide. It does not need oxygen in the same way, and unlike the enzyme pathway, part of it is not performed by human cells at all.

The enterosalivary nitrate cycle

The second pathway takes a longer route than it first appears:

  • Dietary nitrate comes in, largely from leafy greens and beets.
  • It is absorbed from the gut into the bloodstream.
  • The salivary glands take it up and concentrate it — markedly above its level in blood — and secrete it into the mouth.
  • Oral bacteria reduce that nitrate to nitrite.
  • The nitrite is swallowed.
  • Downstream conversion to nitric oxide follows.

Nitrate you ate makes a detour through your mouth before the body can use it this way.

Your bacteria handle the first conversion

This is the part most people have not heard.

Human cells do not efficiently reduce nitrate to nitrite. Oral bacteria do. The step that makes dietary nitrate usable by this pathway is carried out by organisms living on your tongue — which makes them a functional part of the pathway rather than bystanders in it.

Only some bacteria can do it

Not every oral organism carries the machinery. The genera most associated with nitrate reduction in the mouth are Rothia, Neisseria, Veillonella and Actinomyces, and they tend to be most abundant on the back of the tongue — which is also where the environment suits the conversion.

Presence and function are different questions

Identifying one of those genera tells you an organism associated with nitrate reduction is present. It does not establish that the capability is there, because carriage of the relevant gene varies between strains of the same genus.

The narrower and more answerable question is whether the machinery itself is present, and how much of it.

What shapes a nitrate-reducing community

Dietary nitrate is the substrate; without it there is nothing to reduce. Antimicrobial mouthwash acts on the community broadly, and chlorhexidine in particular has been shown to reduce these organisms substantially. Smoking, antibiotics, saliva flow and the overall ecology of the mouth all play a part.

What you can do

  • Eat nitrate-rich foods — leafy greens, beets, root vegetables.
  • Keep a routine oral hygiene practice.
  • Think of mouth care as tending a community rather than sterilising one.
  • See your dentist.
  • Measure, if you are curious where your capacity sits.

Where the research is

This pathway is well characterised in parts and still being worked out in others.

Well established
  • Oral bacteria reduce dietary nitrate to nitrite; human cells do not perform this step efficiently.

  • The salivary glands actively concentrate nitrate from blood and secrete it into the mouth.

  • Nitric oxide is involved in the regulation of vascular tone.

Supported by growing evidence
  • A nitrate-reducing oral community has been studied in relation to cardiovascular and exercise physiology.

  • Chlorhexidine rinses substantially reduce oral nitrate-reducing bacteria and nitrite production.

  • Reduced nitrate-reduction capacity has been reported in periodontitis.

Still being studied
  • How much an individual's nitrate-reducing capacity varies day to day, and what moves it durably.

  • Which other oral mechanisms contribute to nitrate reduction alongside the well-characterised ones.

In context

What shapes the nitrate-reducing side of a community.

Diet

The pathway needs substrate. Nitrate-reducing capacity with no dietary nitrate has nothing to act on, which is why the two are read together.

The rest of the pathway

A measurement of the oral step says nothing about what happens downstream, which depends on physiology a saliva sample does not reach.

Oral care habits

Antimicrobial rinses act on the whole community. What is used, and how often, shapes this side of it.

Time

Communities move. One sample describes the capacity present on one day.

How OraPath measures this

The Oral Balance Test measures narG, a bacterial gene encoding nitrate reductase, attributed to four genera that carry it: Rothia, Neisseria, Veillonella and Actinomyces. Detecting the gene means the machinery for that first conversion is present, not merely that an organism associated with it is.

Those four detections produce the Nitric Oxide System score, which describes the oral side of the pathway. narG is a core, well-characterised nitrate-reduction target; it is not the only mechanism in the oral microbiome.

Measure your nitrate-reducing capacity.

Curious what your oral microbiome looks like? The Oral Balance Test measures targeted organisms and microbial functions from a saliva sample processed in our Norman, Oklahoma laboratory — including the Nitric Oxide System score, the oral side of the nitrate pathway.

Common questions

Which mouth bacteria help make nitric oxide?

The genera most associated with nitrate reduction in the mouth are Rothia, Neisseria, Veillonella and Actinomyces. They are generally most abundant on the back of the tongue.

Does mouthwash affect nitric oxide?

Antimicrobial rinses act on the oral community broadly rather than selectively. Chlorhexidine in particular has been shown to substantially reduce nitrate-reducing bacteria and the nitrite they produce. Over-the-counter rinses differ by active ingredient.

Are beets good for nitric oxide?

Beets are among the richest dietary sources of nitrate, along with leafy greens. Nitrate is the substrate this pathway starts from.

What is narG?

A bacterial gene encoding nitrate reductase — the enzyme that performs the conversion from nitrate to nitrite. Detecting the gene establishes that the machinery is present, rather than inferring it from which species were found.

Can a saliva test measure nitric oxide?

No. Nitric oxide is short-lived and is produced throughout the body. What a saliva test can measure is the bacterial capacity for the first conversion step in the mouth.

Does the OraPath test measure nitric oxide directly?

No. It measures narG, the gene behind the bacterial conversion of nitrate to nitrite, and reports that as the Nitric Oxide System score. That is the oral side of the pathway, not a measurement of nitric oxide in your body.

References

  1. Rosier BT, Takahashi N, Zaura E, Krom BP, Marsh PD. The importance of nitrate reduction for oral health. J Dent Res. 2022;101(8):887–897.
  2. Rosier BT, Moya-Gonzalvez EM, Corell-Escuin P, et al. Nitrate reduction capacity of the oral microbiota is impaired in periodontitis. Int J Oral Sci. 2024;16:3.
  3. Hezel MP, Weitzberg E. The oral microbiome and nitric oxide homeostasis. Free Radic Biol Med. 2015;105:48–57.
  4. Vanhatalo A, Blackwell JR, L'Heureux JE, et al. Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans. Free Radic Biol Med. 2018;124:21–30.
  5. Rosier BT, Buetas E, Moya-Gonzalvez EM, et al. Nitrate as a potential prebiotic for the oral microbiome. ISME J. 2020;14:2459–2469.

Laboratory developed test · for adjunctive clinical use · not FDA cleared.