If you’ve ever felt like you’re doing everything right—eating well, taking supplements, trying to “fix” your gut—and still not seeing results, this Armchair Expert episode gets at why.
Colleen Cutcliffe, PhD, co-founder and CEO of Pendulum Therapeutics, joined Dax Shepard and Monica Padman to unpack what’s really going on inside the gut. The conversation moves from Colleen’s personal story of starting a company after her premature daughter required early antibiotics to the bigger idea: that many of today’s chronic health challenges trace back to a disrupted microbiome. Together, they talk about what makes a healthy gut, key microbial species in the microbiome, the gut-brain connection, and more.
The microbiome as an ecosystem
Early in the episode, Colleen reframes the way we think about our bodies. Our microbes aren’t just along for the ride. They’ve evolved with us.
“Your microbiome is all these bacteria and viruses and fungi… [they’re] sort of everywhere… We’ve really coevolved with them… we’re both getting benefit.”
That relationship is foundational. When it’s working, your microbiome helps regulate metabolism, support the gut lining, and communicate with your immune system and brain. When it’s not, the effects show up far beyond digestion.
What’s gone wrong
Dax, Monica and Colleen talk about the challenges to a healthy microbiome and how we’ve (accidentally) spent decades trying to eliminate microbes without understanding their role.
“We’ve… ruined an entire ecosystem that’s actually here to benefit our health.”
Antibiotics are a clear example. They’re essential in many cases, but they don’t discriminate. They remove harmful bacteria—and beneficial ones right alongside them.
That disruption can start early. Research discussed in the episode links frequent antibiotic exposure in infancy to long-term changes in metabolic and immune health. And for some people, key microbes don’t fully recover.
This is the underlying tension: modern medicine has solved acute problems, but often at the expense of long-term microbial balance.
Why certain microbes matter more than others
Not all probiotics are created equal—a point Colleen returns to throughout the episode.
Rather than thinking about probiotics broadly, she focuses on specific strains with defined functions. In particular, microbes that directly influence how the body processes food and regulates hunger. GLP-1 is a hormone that plays a central role in appetite signaling. It’s part of your body’s natural feedback system, helping you feel full and maintain metabolic balance.
“There are two strains… able to directly stimulate your body’s natural GLP-1.”
One of these strains, Akkermansia muciniphila, is also one of the key microbes linked to gut barrier function and metabolic health—areas that are often compromised in people with obesity, prediabetes, or type 2 diabetes.
When these microbes are missing, it’s not just digestion that changes.
The microbiome is still a young science
The ability to study the microbiome at scale only emerged in the past couple of decades, alongside advances in DNA sequencing. What we know now is growing quickly—but it’s still early. There’s real science, but also a lot of noise.
What’s becoming clearer is that diversity and function matter more than simply adding more bacteria. The goal isn’t quantity. It’s restoring the right ecosystem.
A different way to think about gut health
Gut health isn’t about eliminating symptoms or layering on supplements. It’s about rebuilding a system that’s meant to work together.
When the microbiome is resilient, it can recover from disruptions. It can adapt. It can support your health in ways that go far beyond the gut.
That’s the idea behind why Colleen and the other founders started Pendulum: not just adding probiotics, but restoring missing functions in the microbiome. Because at its core, this isn’t about fixing one symptom; it’s about restoring balance to the system that underlies them all.
Content is for educational purposes only and has not been evaluated by the Food & Drug Administration. Statements and products are not intended to diagnose, treat, cure, or prevent any disease.
