Systems Biology of the Brain–Gut–Microbiome

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.

Guest-at-a-Glance

💡 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

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