Ava Durgin is the Assistant Health Editor at mindbodygreen. She is a recent graduate from Duke University where she received a B.A. in Global Health and Psychology. In her previous work, Ava served as the Patient Education Lead for Duke Hospital affiliated programs, focusing on combating food insecurity and childhood obesity.
Image by Charles Akle x mbg creative
September 23, 2025
Ever had “butterflies in your stomach” before a big event? Or felt that sinking feeling in your gut when something goes wrong? These aren’t just poetic metaphors—your brain and gut are in constant communication via a sophisticated system called the gut-brain axis.
But how does it work, and why does it matter for your overall health? Charles Akle, M.D., physician and gut microbiome expert, helps break down this fascinating connection.
The gut-brain axis: Two communication systems
Think of the gut-brain axis as a dual-channel communication network, much like a computer. Akle uses metaphors to explain these two main pathways:
The Hardwired LAN System (Nerves)The gut communicates with the brain through a network of nerves, particularly the vagus nerve, which acts like a direct cable linking your digestive system to your brain. This nerve sends signals about digestion, immune responses, and gut conditions to your brain, influencing mood and behavior.
The Wi-Fi System (Bloodborne Pathways)Information also travels through blood and lymphatic systems, where immune cells, hormones, and microbial metabolites like short-chain fatty acids serve as messengers. This “Wi-Fi” connection enables chemical signals from the gut to impact brain function, mood, and stress levels.
Together, these systems form a seamless dialogue between your brain and gut, constantly exchanging information to maintain balance and health.
The body’s largest immune organ
What many don’t realize is that the gut is not only central to digestion but also the body’s largest immune organ1. The last 18 inches of the small intestine, near the appendix, are packed with immune tissue.
Specialized immune cells, such as M cells, act as environmental sensors, detecting harmful bacteria like Salmonella or Shigella in minuscule amounts.
Once an invader is identified, these cells pass the information to dendritic cells—Akle tells us to think of them as border guards at an airport, checking IDs and deciding whether to let someone in.
If the dendritic cells sense a threat, they activate immune responses, sending warnings through the nerves and bloodstream to the brain. This mechanism ensures your body can quickly respond to harmful invaders while tolerating harmless ones, like food particles or beneficial bacteria.
Microbes, neurotransmitters, & mood
Serotonin: Often called the “feel-good” hormone, serotonin3 regulates mood, sleep, and appetite. Surprisingly, over 90% of serotonin4 is produced in the gut.
GABA: This neurotransmitter calms the nervous system and helps reduce anxiety.
Dopamine: Known for its role in reward and motivation, gut microbes also support dopamine production.
The vagus nerve: Your gut’s direct line to the brain
The vagus nerve plays a central role in gut-brain communication. This nerve transmits signals about gut conditions directly to the brain and mediates reflexes like digestion and stress responses.
It’s a two-way street: while the brain can influence gut activity, such as slowing digestion during stress, the gut can also send calming or distress signals to the brain, depending on its state.
Stimulating the vagus nerve—through practices like deep breathing, meditation, or even cold exposure—has been shown to reduce stress6 and promote a sense of calm.
Why does this matter?
The gut-brain axis impacts nearly every aspect of your health, from immunity to emotional resilience. Here’s what it influences:
Mood and behavior: Dysbiosis (an imbalanced gut microbiome) is linked to anxiety, depression7, and even autism8.
Cognition and memory: Emerging research shows gut health may affect learning and memory.9
Immunity: The gut’s immune system acts as a first line of defense against pathogens.
Stress resilience: The hypothalamic-pituitary-adrenal (HPA) axis, part of the gut-brain axis, regulates cortisol (the stress hormone), helping you adapt to challenges.
The future of gut-brain research
With growing evidence of the gut-brain connection, researchers are exploring new therapies for mental and neurological disorders by targeting the microbiome.
Probiotics, dietary interventions, and even fecal microbiota transplants (yes, you read that right!) are being studied for their potential to restore balance in the gut and improve brain health.
The takeaway
The gut-brain axis is a remarkable system that highlights the importance of viewing health holistically. From influencing emotions to shaping immune responses, the communication between your gut and brain goes far beyond digestion.
By nurturing your gut through a balanced diet, stress management, and proper care of your microbiome, you can support not only your physical health but also your mental and emotional well-being.
