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In this episode of Longevity by Design, host Dr. Gil Blander sits down with Dr. Emeran Mayer, Executive Director at the UCLA Center for Neurobiology of Stress and Resilience and founder of Mayer Interconnected. They explore the science behind the gut-brain connection and its role in shaping health and longevity.
Emeran explains how signals flow between the brain, gut, and microbiome, influencing everything from digestion to emotions. He breaks down how modern diets, especially ultra-processed foods, disrupt the natural balance between humans and gut microbes—a relationship refined over thousands of years. The conversation highlights why early life exposure to antibiotics can have lasting effects on microbiome resilience, and how lifestyle choices like diet and exercise remain powerful tools for supporting gut-brain health at any age.
The discussion closes with a look toward the future of gut-brain science, including engineered probiotics and the promise of more targeted therapies. Emeran shares practical habits for better gut-brain health and cautions against quick-fix “biohacking,” encouraging a return to whole foods, movement, and mindful living.
💡 Name: Emeran Mayer
💡 What he does: Executive Director and Founder
💡 Company: Mayer Interconnected
💡 Noteworthy: Internationally recognized for his research on the gut-brain-microbiome connection, with deep expertise in how diet, emotion, and microbes shape lifelong health.
💡 Where to find him: https://www.linkedin.com/in/emeranmayer/
Episode highlights:
[00:00:00]: Introduction
[00:01:04]: Background in Gut–Brain Science
[00:03:04]: Early Influences and Career Path
[00:06:07]: Focus on Irritable Bowel Syndrome
[00:07:28]: Defining Irritable Bowel Syndrome
[00:08:40]: Evolving Understanding and Treatment of IBS
[00:10:22]: How the Gut and Brain Communicate
[00:13:32]: Sensation, Pain, and Visceral Hypersensitivity
[00:15:29]: Attention, Perception, and the Role of the Brain
[00:17:06]: Regulation of Sensitivity and Interventions
[00:18:25]: Bidirectional Brain–Gut System
[00:19:40]: Hormonal Signaling from Gut to Brain
[00:22:06]: Shared Biological Language of Gut, Brain, and Microbes
[00:24:08]: Microbiome’s Role in Gut–Brain Communication
[00:26:16]: Systems Biology and Complexity in Human Health
[00:29:01]: Evolution, Symbiosis, and Environmental Mismatch
[00:31:41]: Impact of Ultra-Processed Foods
[00:36:16]: Restoring Gut–Brain Health Through Diet and Lifestyle
[00:37:16]: Emotions and Their Effects on Gut Function
[00:42:03]: Antibiotics, Microbiome Resilience, and Early Life Impact
[00:46:25]: Aging, Microbiome, and Environmental Factors
[00:49:33]: Future Directions in Gut–Brain Science
[00:51:54]: Bioengineered Probiotics and Therapeutic Potential
[00:56:00]: Rapid Fire: Habits, Foods, and Beliefs for Gut–Brain Health
[01:00:31]: Closing Remarks and Takeaways
Key Insights
The Gut-Brain Connection Is a Two-Way Street
The gut and brain don’t just send messages to each other, they form a single, dynamic system that shapes everything from digestion to mood. Signals travel both ways: the brain’s emotional state can trigger gut reactions, while changes in the gut, like what you eat or how your microbes shift, send signals right back to your brain. This system includes nerves, hormones, and immune messengers, not just one simple pathway. When the system is balanced, most signals operate in the background, keeping you feeling normal. But stress, inflammation, or dietary shifts can disrupt this balance and make the gut’s signals much louder or harder to ignore. Understanding this loop helps explain why gut pain can feel so linked to anxiety, and why managing stress or changing your diet can help both body and mind.
Early Microbiome Disruptions Can Have Lasting Effects
Your gut’s resilience starts early in life. The first three years are a critical window when diet, environment, and even medications like antibiotics shape your gut microbiome for years to come. If you disrupt this system early, say, by overusing antibiotics, you risk making the microbiome less diverse and less able to bounce back from future challenges. This can affect how your gut and brain talk to each other and may set the stage for chronic health issues down the line. While healthy adults can often recover from short antibiotic courses, repeated disruptions or early-life stressors can make it hard to rebuild a balanced gut ecosystem. Supporting a diverse microbiome with a varied, plant-based diet and avoiding unnecessary antibiotics can help keep this system strong and resilient.
Modern Diets Challenge Our Ancient Gut-Microbe Partnership
For most of human history, diets featured whole, plant-based foods with little processing. This nourished a diverse gut microbiome, which in turn supported health and longevity. In just a few generations, ultra-processed foods loaded with sugar, fat, and salt have become the norm. These modern diets feed the wrong microbes, weaken the gut’s defenses, and disrupt the feedback loop between gut and brain. Evolution hasn’t had time to adapt our bodies to these rapid changes, creating a mismatch that drives chronic disease. The good news: you still have control. Prioritizing whole, fiber-rich foods and limiting processed items can restore a healthier relationship with your microbiome and improve both gut health and mental well-being. Small, daily choices around food and movement make a big difference over time.
The Overuse of Antibiotics in Early Life
Antibiotics are often prescribed to children for viral infections, even though these drugs do not treat viruses. This overuse can disrupt the development of the gut microbiome, especially during critical early years. Such disruptions can have long-term effects on health and resilience. The discussion underscores that most childhood colds do not benefit from antibiotics and that restraint is important for lifelong gut health.
“This is something that we're seeing: today's widespread overuse of non-medically indicated antibiotics, particularly early on in life. Ninety percent of these colds or upper respiratory tract infections are caused by viruses, which will not respond to antibiotics.”
The Shift in Understanding Irritable Bowel Syndrome
For decades, irritable bowel syndrome (IBS) was thought to be solely a gut disorder, focused on abnormal contractions or motility. Over time, research revealed that IBS is best understood as a disorder of altered brain-gut interactions, not just a gut problem. This new perspective has changed both how the condition is studied and how it is treated, reflecting the complex communication between mind and body.
“This was considered a gut disease. People involved in this were absolutely convinced it’s an abnormality of gut contractions or motility, but in the long term, this was a big battle to accept this new model of basically saying this is a disorder of altered brain-gut interactions. It’s not a gut disease.”
Ultra-Processed Foods and the Modern Microbiome Mismatch
Modern diets filled with ultra-processed foods have disrupted the long-evolved partnership between humans and their gut microbes. Unlike the plant-based, minimally processed diets of our ancestors, today’s foods are often designed to be addictive and are loaded with salt, sugar, and fat. This mismatch between our biology and modern eating habits can weaken the gut microbiome and contribute to chronic disease.
“This symbiosis has evolved and is optimized for the interaction of our gut and microbiome with natural foods. What has happened now in the last hundred years? Obviously, an explosion of chemicals and processes that are applied to our food. The main driving force behind it is not so much preservation, but really to make people hooked on these foods.”
The Future of Microbiome Research and Bioengineered Probiotics
bioengineered probiotics. These beneficial microbes can be designed to deliver specific effects, such as homing in on inflammation or breaking down harmful substances like microplastics. While this approach holds promise for treating diseases, it also raises questions about the risks of altering ancient biological systems.
“The idea is that microbes are perfect vehicles to carry a target or a cargo to a particular target. You can reprogram them so they actually hone in on the inflammation. This approach has been tested in mouse models and pig models and is now going into first-phase clinical trials.”
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