BiotiQuest® Gut Health & Probiotics Blog with Martha Carlin

How the Gut Microbiome Influences Nitric Oxide Signaling and Flow

Martha Carlin | Feb 03, 2026 |

Nitric oxide is often talked about as a molecule you “boost.” It shows up in supplement marketing, athletic performance claims, and cardiovascular headlines as something to increase, enhance, or optimize.

But that framing misses something essential.

Nitric oxide behaves less like a substance you add and more like a signal that emerges when conditions are right—when flow is supported, resistance is low, and communication across tissues remains coherent. When those conditions are disrupted, nitric oxide signaling becomes unreliable, no matter how many ingredients are supplied upstream.

For decades, nitric oxide research focused almost entirely on blood vessels. The story was told as one of smooth muscle relaxation and vascular tone. What keeps showing up more recently—across cardiovascular research, metabolic studies, and microbiome science—is that nitric oxide availability tracks more closely with terrain than with isolated inputs.

And much of that terrain begins in the gut.

Nitric Oxide and Flow

Nitric oxide allows blood vessels to relax and adapt. When it’s available, circulation adjusts smoothly to changing demands. Oxygen delivery improves. Waste removal stays efficient. Pressure is distributed rather than concentrated.

When nitric oxide signaling is constrained, the system compensates. Vessels stiffen. Pressure builds. The body finds workarounds—often quietly at first, often years before symptoms are recognized—but never without cost.

Importantly, nitric oxide doesn’t operate in isolation. It reflects the physical and chemical environment it moves through. Vessels don’t simply “respond” to nitric oxide; they respond within the context of membranes, ions, glycocalyx integrity, and redox balance.

This is why nitric oxide is better understood as a readout of system health rather than a lever to be pulled.

Two Pathways, Two Worldviews

The body has more than one way to generate nitric oxide.

One route uses amino acids like L-arginine and enzyme-driven pathways that are well described in textbooks. This pathway is relatively direct and tightly regulated.

The second route relies on dietary nitrates, commonly found in foods like leafy greens and beets. This pathway is older, less linear, and far more dependent on the internal environment—particularly the microbial ecosystem and the interfaces it helps maintain.

This nitrate-dependent pathway is not a backup system. It is a parallel, deeply conserved biological route that behaves very differently depending on context. It is also the pathway most sensitive to disruption by modern life.

The Microbiome as a Complex Production Environment

A healthy microbiome does, in many ways, resemble a factory—but not a linear one. It’s a complex, distributed production environment where many microbial “workers” operate simultaneously, responding to local conditions and to one another rather than following a single assembly line.

These microbes don’t perform isolated steps in sequence. They work in parallel, shaping pH, redox balance, ionic availability, bile structure, and membrane behavior all at once. The output isn’t a single product, but a set of conditions.

When that production environment is functioning well, nitrate and nitrite chemistry becomes accessible to the body’s signaling networks. Nitric oxide doesn’t have to be forced. It emerges because the factory floor is stable, supplied, and responsive.

When the workforce is depleted or the environment disrupted—by antibiotics, chronic stress, environmental chemicals, or a narrow diet—the machinery is still there, but coordination is lost. Raw materials accumulate without being integrated, and signaling becomes unreliable.

This is why the more relevant question is rarely, “Am I getting enough nitrates?” and more often, “Is the internal environment capable of using what’s already there?”

Terrain Over Ingredients

You can eat all the leafy greens in the world, but if the microbial ecosystem is depleted or destabilized, nitric oxide signaling will remain inconsistent.

This pattern shows up across biology. Signals don’t fail because ingredients are missing; they fail because interfaces lose coherence. Membranes stiffen. Surfaces become noisy. Communication becomes fragmented.

The gut microbiome plays a central role in maintaining those interfaces—not just in the digestive tract, but system-wide. When microbial ecosystems are resilient, signaling pathways tend to recover across multiple systems at once. When they are not, signaling becomes increasingly dependent on force, compensation, and external support.

A Practical Example: Beet Kvass

One simple way to support nitric oxide signaling—without trying to force it—is through traditional fermentation. Beet kvass is a good example.

Beets are naturally rich in nitrates, but fermentation changes the context in which those nitrates are delivered. The process pre-conditions the chemistry, introduces living microbes, and supports gut interfaces at the same time. Rather than relying on isolated inputs, beet kvass works by improving the terrain the signal moves through.

This matters because biological systems rarely respond well to isolated amplification. They respond to changes in environment.

Fermentation does several things at once:

  • It alters the chemical form and accessibility of compounds before they enter the body
  • It supports microbial ecosystems rather than bypassing them
  • It reduces resistance at biological interfaces instead of demanding a specific outcome
  • This is one reason fermented foods appear across cultures long before anyone measured nitric oxide. They don’t target a single molecule. They support flow by stabilizing microbial ecosystems and reducing friction at biological surfaces.

We’ve shared our simple beet kvass recipe as an accessible way to support this process using food rather than supplements.

Interfaces, Not Isolated Parts

Short-chain fatty acids like butyrate are often discussed in terms of inflammation, but their deeper role is structural. They help support the integrity of gut interfaces and the signaling surfaces that depend on them.

When those interfaces are stable, noise decreases. Signals propagate with less distortion. Nitric oxide signaling becomes more reliable—not because nitric oxide is being “increased,” but because the system can carry the signal without interference.

Nothing here acts alone. Nitric oxide reflects the state of the system it moves through.

What Disrupts Nitric Oxide Signaling in Modern Life

Several modern pressures quietly erode the terrain nitric oxide depends on:

  • Repeated antibiotic exposure that reduces microbial diversity and resilience
  • Chronic psychological stress that alters gut–brain signaling
  • Environmental chemicals, including surfactants and disinfectants that disrupt membranes
  • Highly processed diets that provide inputs without microbial context
  • The loss of fermented foods that historically helped stabilize interfaces

These pressures don’t eliminate nitric oxide pathways. They make them fragile.

Supporting Nitric Oxide Signaling in Practice

In practice, supporting nitric oxide signaling means supporting the systems that allow it to emerge.

This is the intent behind our Heart Centered formulation. Rather than targeting nitric oxide directly, it’s designed to support microbial balance, signaling surfaces, and the biochemical context that nitric oxide depends on—particularly within the gut–vascular interface.

By addressing microbial resilience, mineral availability, and signaling interference together, Heart Centered works with the body’s existing pathways rather than trying to override them. The goal is not stimulation, but reliability—supporting flow without forcing outcomes.

Returning to Flow

When we talk about nitric oxide, we are ultimately talking about flow—of blood, information, and energy across living surfaces.

What decades of nitric oxide research, and now microbiome science, continue to reveal is that flow cannot be commanded. It has to be supported. Signals don’t move well through stiff, noisy, depleted systems. They move through environments that are supplied, buffered, and biologically coherent.

The gut microbiome sits at the center of that coherence. When its ecosystems are intact, nitric oxide signaling tends to recover across multiple systems at once—vascular, metabolic, and neurological. When they are not, nitric oxide becomes something people try to replace, stimulate, or override.

The more durable question is not how to increase nitric oxide, but how to rebuild the conditions that allow flow to return on its own. That’s where lasting resilience lives.

With gratitude,

Martha Carlin photo Martha Carlin, is a “Citizen Scientist”, systems thinker, wife of Parkinson’s warrior, John Carlin, and founder of The BioCollective , a microbiome company expanding the reach of science and BiotiQuest, the first of it’s kind probiotic line. Since John’s diagnosis in 2002, Martha began learning the science of agriculture, nutrition, environment, infectious disease, Parkinson’s pathology and much more. In 2014, when the first research was published showing a connection between the gut bacteria and the two phenotypes of Parkinson’s, Martha quit her former career as a business turnaround expert and founded The BioCollective to accelerate the discovery of the impact of gut health on all human disease. Martha was a speaker at the White House 2016 Microbiome Initiative launch, challenging the scientific community to “think in a broader context”. Her systems thinking background and experience has led to collaborations across the scientific spectrum from neuroscience to engineering to infectious disease. She is a respected out of the box problem solver in the microbiome field and brings a unique perspective to helping others understand the connections from the soil to the food to our guts and our brains.

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