Are Gut Metabolites the Secret to Longevity?

Article Written By Dr. Daniel Winer, Buck Institute for Research on Aging & Nicholas Tubach, Co-Founder of Propion Inc.

By now, most health-conscious readers know that trillions of bacteria live inside our digestive tract. This dynamic ecosystem—known as the gut microbiome—shapes everything from immunity to mood. But here’s the twist: it’s not the bacteria themselves pulling the strings. It’s their chemical output.

These tiny messengers, called gut metabolites, are the real conductors of the body’s symphony of health. They dictate communication between the gut and the rest of the body, turning biological switches on or off to regulate digestion, hormones, inflammation, and even cellular regeneration.

Some metabolites heal; others harm. The good ones—produced by a healthy, diverse microbiome—help regenerate the gut wall, protect your cells from oxidative stress, and calm inflammation. The bad ones, on the other hand, fan the flames of chronic disease, accelerate tissue breakdown, and quietly push the body toward aging.

What Happens When Gut Metabolites Fall Out of Balance?

As we age, our internal chemistry begins to shift. Levels of protective metabolites decline while pro-inflammatory compounds rise. Combine that with a diet high in processed foods and low in fiber, and the imbalance worsens dramatically. By midlife, most people produce less than half of the beneficial gut metabolites they once did.

This decline sets off a chain reaction: inflammation outpaces repair, oxidative stress builds up, and tissues—from the gut wall to the brain—begin to deteriorate. The immune system weakens, the gut barrier grows leaky, and the brain becomes more vulnerable to environmental toxins and plaques.

What makes this particularly concerning is that the process is largely silent. You don’t feel it happening, but the metabolic shift quietly drives many of the degenerative changes we associate with “normal” aging.

Why Is Tryptophan Metabolism So Crucial for Healthy Aging?

One of the most fascinating—and overlooked—pathways in this story involves tryptophan, an amino acid best known for its role in producing serotonin and melatonin. Beyond its mood and sleep benefits, tryptophan is also a building block for some of the most potent anti-aging metabolites our gut can produce.

When the right bacteria metabolize tryptophan, they generate a family of compounds called indoles, including two standout molecules: indole-3-propionic acid (Propion 1) and indolepropionamide (Propion 2). Both exhibit neuroprotective, anti-inflammatory, and regenerative properties. Propion 1, for example, has been shown to promote liver and gut regeneration while guarding the brain against neurotoxic plaques. Propion 2, though less studied, is equally promising—it has even extended lifespan by 300 percent in early research models.

The problem? As we age, the body starts metabolizing tryptophan through human enzymes—TDO and IDO—that divert it away from these beneficial bacterial pathways. The result: fewer protective indoles, more harmful metabolites, and a weakened cellular defense system.

How Can We Rebalance These Pathways Naturally?

That’s where Propion Inc., a longevity-focused biotech startup, steps in. Founded by Dr. Daniel Winer, a physician-scientist at the Buck Institute for Research on Aging, and Nicholas Tubach, a serial health-tech entrepreneur, the company is pioneering a nutritional approach to reboot gut-driven anti-aging mechanisms.

Their flagship formula, Propion BLEND, combines specific nutrients and cofactors that feed beneficial gut bacteria while blocking the TDO and IDO enzymes. The goal: redirect tryptophan metabolism toward producing more Propion 1 and 2.

In a pilot clinical trial, this targeted approach showed extraordinary promise—participants saw an average reduction in biological age of 11 years after 12 months of use. Their immune systems functioned more like those of people a decade younger, confirming what preclinical models had long hinted at: restoring balance to gut metabolites could profoundly influence how we age.

“This corresponds with what we’ve seen from Propion 1 and 2 in models of age- and diet-related dysfunction,” says Dr. Winer. “By restoring this balance, we’re not just treating aging—we’re reprogramming it.”

Where Do Gut Metabolites Fit Into the Future of Longevity?

Gut metabolites may be microscopic, but their influence is massive. They’re the biochemical language linking diet, microbes, and cellular repair. What we’re learning is that aging isn’t simply about time passing—it’s about communication breaking down. When we restore that dialogue between the gut and the rest of the body, we don’t just slow aging; we give the body a chance to self-correct.

The implications stretch far beyond supplements. The future of longevity medicine could revolve around nurturing the microbiome to generate the right molecules at the right time. In short, longevity might just start in the gut—one metabolite at a time.

You can learn more about Propion BLEND at www.propion.com. The company is currently raising a funding round; interested parties can contact nicholas@propion.com for details.